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  1. 77 FR 65582 - Pfizer Therapeutic Research, Pfizer Worldwide Reasearch & Development Division, Formerly Known as...

    Science.gov (United States)

    2012-10-29

    ... Research, Pfizer Worldwide Reasearch & Development Division, Formerly Known as Warner Lambert Company... workers of Pfizer Therapeutic Research, Pfizer Worldwide Research & Development Division, formerly known... follows: All workers of Pfizer Therapeutic Research, Pfizer Worldwide Research & Development Division...

  2. 77 FR 35060 - Pfizer Therapeutic Research, Formerly Known as Warner Lambert Company, Pfizer Worldwide Research...

    Science.gov (United States)

    2012-06-12

    ... Research, Formerly Known as Warner Lambert Company, Pfizer Worldwide Research & Development Division... December 2, 2011, applicable to workers of Pfizer Therapeutic Research, Pfizer Worldwide Research... Worldwide Research & Development Division, Antibacterial Research Unit, Pharmacokinetics, Dynamics and...

  3. 78 FR 28630 - Pfizer Therapeutic Research, Pfizer Worldwide Research & Development Division, Formerly Known as...

    Science.gov (United States)

    2013-05-15

    ... Research, Pfizer Worldwide Research & Development Division, Formerly Known as Warner Lambert Company... Groton, Connecticut location of Pfizer Therapeutic Research, Pfizer Worldwide Research & Development... Worldwide Research & Development Division, formerly known as Warner Lambert Company, Comparative Medicine...

  4. Ravimifirmat Pfizer asus juhtima lätlanna / Agnes Ojala

    Index Scriptorium Estoniae

    Ojala, Agnes

    2007-01-01

    Ilmunud ka: Delovõje Vedomosti 28. märts lk. 15. Ravimifirma Pfizer Eesti ja Läti filiaali liitmisel sai firma uueks tegevjuhiks Pfizer Läti filiaali juhtinud Laima Rutka. Vt. samas: Uus ravim suitsu vastu

  5. International Legal and Ethical Considerations at Pfizer, Inc.

    Science.gov (United States)

    Pagnattaro, Marisa Anne

    2005-01-01

    Pfizer, Inc. (hereinafter Pfizer), a U.S.-based pharmaceutical company, states that it is committed to being an "exemplary corporate citizen" that is "dedicated to discovering and developing innovative medicines and making them available to people all around the world." Pfizer boasts about its philanthropic focus, yet, like any…

  6. Integrase of Mason-Pfizer monkey virus

    Czech Academy of Sciences Publication Activity Database

    Snášel, Jan; Krejčík, Zdeněk; Jenčová, Věra; Rosenberg, Ivan; Ruml, Tomáš; Alexandratos, J.; Gustchina, A.; Pichová, Iva

    2005-01-01

    Roč. 272, č. 1 (2005), s. 203-216 ISSN 1742-464X R&D Projects: GA AV ČR(CZ) IAA4055304 Institutional research plan: CEZ:AV0Z4055905 Keywords : integrase * Mason-Pfizer monkey virus * HIV-1 Subject RIV: CE - Biochemistry

  7. Structural study of Mason-Pfizer monkey virus protease

    Czech Academy of Sciences Publication Activity Database

    Veverka, V.; Bauerová, Helena; Hrabal, R.; Pichová, Iva

    2002-01-01

    Roč. 269, - (2002), s. 57-58 ISSN 0014-2956. [Meeting of the Federation of European Biochemical Societies /28./. 20.10.2002-25.10.2002, Istanbul] R&D Projects: GA ČR GA203/00/1241 Institutional research plan: CEZ:AV0Z4055905 Keywords : Mason-Pfizer monkey virus Subject RIV: CE - Biochemistry

  8. Autoprocessing of Mason-Pfizer monkey virus protease

    Czech Academy of Sciences Publication Activity Database

    Bauerová, Helena; Rumlová, Michaela; Hunter, E.; Ruml, T.; Pichová, Iva

    2001-01-01

    Roč. 77, č. 2 (2001), s. 131-133 ISSN 0168-1702 R&D Projects: GA ČR GA203/00/1241; GA AV ČR IAA4055904 Grant - others:Fogarty International Award(US) TW00050 Institutional research plan: CEZ:AV0Z4055905 Keywords : Mason-Pfizer monkey virus Subject RIV: CE - Biochemistry Impact factor: 1.806, year: 2001

  9. Pfizer and the Challenges of the Global Pharmaceutical Industry 2013 (B)

    DEFF Research Database (Denmark)

    Kratochvil, Renate; Nell, Phillip Christopher

    2017-01-01

    This is part of a case series. The overall case focuses on the overall pharmaceutical market, such as industry structure and trends, as well as the strategic position of innovative (R&D intensive) pharmaceutical companies. Case A starts with a description of Pfizer struggling to hold its position...... as an industry leader and questions whether this is indicative for the current developments of the entire industry, putting big pharmaceutical companies’ power and influence under pressure. Such trends are, for example, slower sales growth, expiring patents, increasing competition from generics, shorter product...... pharmaceutical companies’ (and in particular Pfizer's) strategic moves (such as mega M&As) to conquer recent trends. The reader is then referred back to Pfizer's situation, its recent strategic initiatives, and competitor’s behaviour. Both cases feature comprehensive information and a large number of tables...

  10. Pfizer and the Challenges of the Global Pharmaceutical Industry 2013 (A)

    DEFF Research Database (Denmark)

    Kratochvil, Renate; Nell, Phillip Christopher

    2018-01-01

    This is part of a case series. The overall case focuses on the overall pharmaceutical market, such as industry structure and trends, as well as the strategic position of innovative (R&D intensive) pharmaceutical companies. Case A starts with a description of Pfizer struggling to hold its position...... as an industry leader and questions whether this is indicative for the current developments of the entire industry, putting big pharmaceutical companies’ power and influence under pressure. Such trends are, for example, slower sales growth, expiring patents, increasing competition from generics, shorter product...... pharmaceutical companies’ (and in particular Pfizer's) strategic moves (such as mega M&As) to conquer recent trends. The reader is then referred back to Pfizer's situation, its recent strategic initiatives, and competitor’s behaviour. Both cases feature comprehensive information and a large number of tables...

  11. Pfizer and the Challenges of the Global Pharmaceutical Industry 2013 (B)

    DEFF Research Database (Denmark)

    Nell, Phillip Christopher

    2013-01-01

    This is part of a case series. The case focuses on describing and analysing the environment, profitability and competitiveness of the global pharmaceutical industry, and to evaluate the current and future strategy of Pfizer. It features a large number of tables with quantitative data that help...... initiatives and responses to the market changes....

  12. Letter to the Editor: Backbone resonance assignment of protease from Mason-Pfizer monkey virus

    Czech Academy of Sciences Publication Activity Database

    Veverka, V.; Bauerová, Helena; Zábranský, Aleš; Pichová, Iva; Hrabal, R.

    2001-01-01

    Roč. 20, - (2001), s. 291-292 ISSN 0925-2738 R&D Projects: GA ČR GA203/00/1241 Grant - others:Fogarty International Award(US) TW00050 Institutional research plan: CEZ:AV0Z4055905 Keywords : Mason-Pfizer monkey virus * retroviral protease Subject RIV: CE - Biochemistry Impact factor: 4.636, year: 2001

  13. Pfizer and the Challenges of the Global Pharmaceutical Industry 2013 (A)

    DEFF Research Database (Denmark)

    Nell, Phillip Christopher

    2013-01-01

    This is part of a case series. The case focuses on describing and analysing the environment, profitability and competitiveness of the global pharmaceutical industry, and to evaluate the current and future strategy of Pfizer. It features a large number of tables with quantitative data that help...... solving the case study. The case starts with a short description of recent important events that might mark a turning point for the whole industry. It then focuses on the overall market on drugs - structure, growth, blockbusters, and the influence of national health care systems. Furthermore, firms’ R...... a number of strategic manoeuvres of major players in the last years. At the end, the reader is referred back to the Pfizer situation and Pfizer’s recent strategic initiatives and responses to the market changes....

  14. AUSTRALIAN COMPETITION AND CONSUMER COMMISSION v PFIZER: EVERGREENING AND MARKET POWER AS A BLOCKBUSTER DRUG GOES OFF PATENT.

    Science.gov (United States)

    Faunce, Thomas

    2015-06-01

    In Australian Competition and Consumer Commission v Pfizer Australia Pty Ltd [2015] FCA 113, the ACCC alleged that Pfizer's "Project LEAP" involved a scheme to lock pharmacists into substituting its generic version of the high sales volume anti-cholesterol drug, patent-expired atorvastatin (Lipitor), which took advantage of a substantial degree of market power for a purpose proscribed by s 46(1)(c) of the Competition and Consumer Act 2010 (Cth). The ACCC also claimed that Pfizer's actions constituted a course of exclusive dealing pursuant to s 47(1)(d) and (e) for the proscribed purpose of lessening competition. Flick J in the Federal Court of Australia, in a judgment heavy with quotations but sparse in reasoning, dismissed the ACCC's Amended Originating Application alleging abuse of market power and ordered the ACCC to pay Pfizer's costs. The ACCC has now appealed the decision. This column explores this case in the context of Pfizer's broader strategies to preserve its income globally from this high sales volume drug in the period following its patent expiration.

  15. Flaws in design, analysis and interpretation of Pfizer's antifungal trials of voriconazole and uncritical subsequent quotations.

    Science.gov (United States)

    Jørgensen, Karsten J; Johansen, Helle Krogh; Gøtzsche, Peter C

    2006-01-19

    We have previously described how a series of trials sponsored by Pfizer of its antifungal drug, fluconazole, in cancer patients with neutropenia handicapped the control drug, amphotericin B, by flaws in design and analysis. We describe similar problems in two pivotal trials of Pfizer's new antifungal agent, voriconazole, published in a prestigious journal. In a non-inferiority trial, voriconazole was significantly inferior to liposomal amphothericin B, but the authors concluded that voriconazole was a suitable alternative. The second trial used amphothericin B deoxycholate as comparator, but handicapped the drug by not requiring pre-medication to reduce infusion-related toxicity or substitution with electrolytes and fluid to reduce nephrotoxicity, although the planned duration of treatment was 84 days. Voriconazole was given for 77 days on average, but the comparator for only 10 days, which precludes a meaningful comparison. In a random sample of 50 references to these trials, we found that the unwarranted conclusions were mostly uncritically propagated. It was particularly surprising that relevant criticism raised by the FDA related to the first trial was only quoted once, and that none of the articles noted the obvious flaws in the design of the second trial. We suggest that editors ensure that the abstract reflects fairly on the remainder of the paper, and that journals do not impose any time limit for accepting letters that point out serious weaknesses in a study that have not been noted before.

  16. The Mason-Pfizer monkey virus internal scaffold domain enables in vitro assembly of human immunodeficiency virus type 1 Gag

    Czech Academy of Sciences Publication Activity Database

    Sakalian, M.; Dittmer, S. S.; Gandy, A. D.; Rapp, N. D.; Zábranský, Aleš; Hunter, E.

    2002-01-01

    Roč. 76, č. 21 (2002), s. 10811-10820 ISSN 0022-538X Grant - others:NIH(US) CA-27834; NIH(US) AI-43230 Keywords : Mason-Pfizer monkey virus Subject RIV: CE - Biochemistry Impact factor: 5.241, year: 2002

  17. Antigenic analysis of the major structural protein of the Mason-Pfizer monkey virus

    International Nuclear Information System (INIS)

    Schochetman, G.; Boehm-Truitt, M.; Schlom, J.

    1976-01-01

    The major internal protein, p27 (m.w. 27,000 daltons) of the Mason-Pfizer monkey virus (MPMV) was purified by gel filtration and ion-exchange chromatography and then used to develop a radioimmunoassay (RIA). This RIA was specific for MPMV because no immunologic cross-reactivity was observed between p27 of MPMV and 13 different RNA tumor viruses of mammalian and avian origin. However, the p27 of MPMV grown in three different primate cells exhibited identical antigenic cross-reactivity. In addition, significant levels of p27 were found only in MPMV-infected cells. These results indicate that synthesis of p27 is induced after virus infection and that p27 represents a viral-coded protein

  18. ABUSO DEL DIRITTO AL BREVETTO E ABUSO DI POSIZIONE DOMINANTE: IL CASO PFIZER

    Directory of Open Access Journals (Sweden)

    Gustavo Ghidini

    2014-12-01

    Full Text Available Even the acquisition – not just the exercise – of a patent (as any other IPR may amount to a misuse if the achievement thereof runs in contrast with the rules governing its entitlement. And if the patent owner enjoys a dominant position, the patent misuse may translate into an abuse of such position under art. 102 TFEU. This appears to be the core of the decision of Council of State as of February 12, 2014, n.693, which settled the Pfizer Italian case, overturning the opposite ruling of Tar Lazio, and thus upholding the previous ICA’ finding of such an abuse. In particular, the circumstances of the case showed that Pfizer’s request and obtainment a European divisional patent – in truth, a divisional patent of another divisional patent – with effects for Italy and Spain (countries where such request had not been filed, was not intended at legitimately acquiring an exclusive right on a self-standing portion of the parental patent, in compliance with the rule of patent ‘unity’, but was actually aimed at achieving, thirteen years after the filing of the parental patent and in contrast with the said rule, a Complementary Protection Certificate (CPC in Italy and Spain, in order to prolong exclusive rights on an active principle which had emerged as de facto standard (hence, the assessment of a dominant position, and which prospective competitors in the Italian market had legitimately come to consider “off patent” from 2009, consequently preparing to enter the market with their “generic” substitutes. The article supports the position of Council of State and the Italian Authority, particularly replying to the critiques expressed by an authoritative scholar, also a lawyer of Pfizer in the captioned case. The Authors, finally, hint to the enforceability, even in absence of a dominant position in strict sense, of patent misuses in the legal perspective of both “relative dominance” and unfair competition.

  19. Molecular organization of Mason-Pfizer monkey virus capsids assembled from Gag polyprotein in .I.Escherichia coli./I..

    Czech Academy of Sciences Publication Activity Database

    Nermut, M. V.; Bron, P.; Thomas, D.; Rumlová, Michaela; Ruml, T.; Hunter, E.

    2002-01-01

    Roč. 76, č. 9 (2002), s. 4321-4330 ISSN 0022-538X R&D Projects: GA ČR GA203/00/1005; GA ČR GA203/98/P151 Institutional research plan: CEZ:AV0Z4055905 Keywords : Mason-Pfizer monkey virus Subject RIV: CE - Biochemistry Impact factor: 5.241, year: 2002

  20. Gag domains of Mason-Pfizer monkey virus mediating assembly of capsids and "Core related" particles in bacteria

    Czech Academy of Sciences Publication Activity Database

    Rumlová, Michaela; Hunter, E.; Nermut, M.; Pichová, Iva; Ruml, T.

    2001-01-01

    Roč. 77, č. 2 (2001), s. 110-113 ISSN 0168-1702 R&D Projects: GA ČR GA203/00/1005 Grant - others:Fogarty International Award(US) TW00050; NIH(US) CA-27834 Institutional research plan: CEZ:AV0Z4055905 Keywords : Mason-Pfizer monkey virus Subject RIV: CE - Biochemistry Impact factor: 1.806, year: 2001

  1. Characterization of Mason--Pfizer monkey virus-induced cell fusion

    International Nuclear Information System (INIS)

    Chatterjee, S.; Hunter, E.

    1979-01-01

    The characteristics and requirements of multinucleate cell (syncytium) induction by Mason--Pfizer monkey virus (M-PMV) on human and non-human primate cells have been investigated. Multinucleate cell induction by this D-type retrovirus shows single-hit kinetics on human foreskin and rhesus monkey fetal lung cells. The peak of syncytium-forming activity in an isopycnic sucrose gradient coincides with the peak of M-PMV virions as assessed by electron microscopy and analysis of viral polypeptides. Unlike the paramyxoviruses, M-PMV does not induce early cell fusion when added in high concentrations to the target cells. Furthermore, multinucleate cell formation is maximal 48 hr postinfection and the size of the syncytia remains constant after this time. Ultraviolet irradiation of M-PMV reduces its ability to form syncytia and to replicate with single-hit kinetics, suggesting that a functional viral genome is required for syncytium formation. Proviral DNA synthesis and assembly of virions are not necessary for cell fusion since the addition of cytosine arabinoside at concentrations which block virus replication has little effect on multinucleate cell formation. Moreover both multinucleate cells lacking detectable intracellular virus polypeptides, and groups of individual, nonfused but brightly staining cells can be observed in immunofluorescence assays at times when multinucleate cell formation is maximal. Cell fusion is inhibited by the addition of cycloheximide during the first 12 hr of infection, suggesting that de novo protein synthesis is required for multinucleate cell formation. The possibility that the translation of genomic RNA yields a fusion-inducing product is discussed

  2. LEAP into the Pfizer Global Virtual Library (PGVL) space: creation of readily synthesizable design ideas automatically.

    Science.gov (United States)

    Hu, Qiyue; Peng, Zhengwei; Kostrowicki, Jaroslav; Kuki, Atsuo

    2011-01-01

    Pfizer Global Virtual Library (PGVL) of 10(13) readily synthesizable molecules offers a tremendous opportunity for lead optimization and scaffold hopping in drug discovery projects. However, mining into a chemical space of this size presents a challenge for the concomitant design informatics due to the fact that standard molecular similarity searches against a collection of explicit molecules cannot be utilized, since no chemical information system could create and manage more than 10(8) explicit molecules. Nevertheless, by accepting a tolerable level of false negatives in search results, we were able to bypass the need for full 10(13) enumeration and enabled the efficient similarity search and retrieval into this huge chemical space for practical usage by medicinal chemists. In this report, two search methods (LEAP1 and LEAP2) are presented. The first method uses PGVL reaction knowledge to disassemble the incoming search query molecule into a set of reactants and then uses reactant-level similarities into actual available starting materials to focus on a much smaller sub-region of the full virtual library compound space. This sub-region is then explicitly enumerated and searched via a standard similarity method using the original query molecule. The second method uses a fuzzy mapping onto candidate reactions and does not require exact disassembly of the incoming query molecule. Instead Basis Products (or capped reactants) are mapped into the query molecule and the resultant asymmetric similarity scores are used to prioritize the corresponding reactions and reactant sets. All sets of Basis Products are inherently indexed to specific reactions and specific starting materials. This again allows focusing on a much smaller sub-region for explicit enumeration and subsequent standard product-level similarity search. A set of validation studies were conducted. The results have shown that the level of false negatives for the disassembly-based method is acceptable when the

  3. Comparison of classical and affinity purification techniques of Mason-Pfizer monkey virus capsid protein: The Alteration of the product by an affinity tag

    Czech Academy of Sciences Publication Activity Database

    Rumlová, Michaela; Benedíková, Jitka; Cubínková, Romana; Pichová, Iva; Ruml, Tomáš

    2001-01-01

    Roč. 23, - (2001), s. 75-83 ISSN 1046-5928 R&D Projects: GA ČR GA203/00/1005 Institutional research plan: CEZ:AV0Z4055905 Keywords : Mason-Pfizer monkey virus * capsid protein Subject RIV: CE - Biochemistry Impact factor: 1.497, year: 2001

  4. Assignment of 1H, 13C, and 15N resonances of WT matrix protein and its R55F mutant from Mason-Pfizer monkey virus

    Czech Academy of Sciences Publication Activity Database

    Vlach, J.; Lipov, J.; Veverka, V.; Rumlová, Michaela; Ruml, T.; Hrabal, R.

    2005-01-01

    Roč. 31, - (2005), s. 381-382 ISSN 0925-2738 R&D Projects: GA ČR GA203/03/0490 Institutional research plan: CEZ:AV0Z4055905 Keywords : Mason-Pfizer monkey virus * NMR resonance assignment * matrix protein Subject RIV: CE - Biochemistry Impact factor: 2.180, year: 2005

  5. Conformational changes of the N-terminal part of Mason-Pfizer monkey virus p12 protein during multimerization

    International Nuclear Information System (INIS)

    Knejzlik, Zdenek; Ulbrich, Pavel; Strohalm, Martin; Lastuvkova, Hana; Kodicek, Milan; Sakalian, Michael; Ruml, Tomas

    2009-01-01

    The Mason-Pfizer monkey virus is a prototype Betaretrovirus with the defining characteristic that it assembles spherical immature particles from Gag-related polyprotein precursors within the cytoplasm of the infected cell. It was shown previously that the N-terminal part of the Gag p12 domain (wt-Np12) is required for efficient assembly. However, the precise role for p12 in mediating Gag-Gag interaction is still poorly understood. In this study we employed detailed circular dichroism spectroscopy, electron microscopy and ultracentrifugation analyses of recombinant wt-Np12 prepared by in vitro transcription and translation. The wt-Np12 domain fragment forms fibrillar structures in a concentration-dependent manner. Assembly into fibers is linked to a conformational transition from unfolded or another non-periodical state to α-helix during multimerization.

  6. Public-private partnerships to build human capacity in low income countries: findings from the Pfizer program

    Directory of Open Access Journals (Sweden)

    Connelly Patrick

    2007-03-01

    Full Text Available Abstract Background The ability of health organizations in developing countries to expand access to quality services depends in large part on organizational and human capacity. Capacity building includes professional development of staff, as well as efforts to create working environments conducive to high levels of performance. The current study evaluated an approach to public-private partnership where corporate volunteers give technical assistance to improve organizational and staff performance. From 2003 to 2005, the Pfizer Global Health Fellows program sent 72 employees to work with organizations in 19 countries. This evaluation was designed to assess program impact. Methods The researchers administered a survey to 60 Fellows and 48 Pfizer Supervisors. In addition, the team conducted over 100 interviews with partner organization staff and other key informants during site visits in Uganda, Kenya, Ghana, South Africa and India, the five countries where 60% of Fellows were placed. Results Over three-quarters of Fellowships appear to have imparted skills or enhanced operations of NGOs in HIV/AIDS and other health programs. Overall, 79% of Fellows reported meeting all or most technical assistance goals. Partner organization staff reported that the Fellows provided training to clinical and research personnel; strengthened laboratory, pharmacy, financial control, and human resource management systems; and helped expand Partner organization networks. Local staff also reported the Program changed their work habits and attitudes. The evaluation identified problems in defining goals of Fellowships and matching Organizations with Fellows. Capacity building success also appears related to size and sophistication of partner organization. Conclusion Public expectations have grown regarding the role corporations should play in improving health systems in developing countries. Corporate philanthropy programs based on "donations" of personnel can help build

  7. Public-private partnerships to build human capacity in low income countries: findings from the Pfizer program.

    Science.gov (United States)

    Vian, Taryn; Richards, Sarah C; McCoy, Kelly; Connelly, Patrick; Feeley, Frank

    2007-03-02

    The ability of health organizations in developing countries to expand access to quality services depends in large part on organizational and human capacity. Capacity building includes professional development of staff, as well as efforts to create working environments conducive to high levels of performance. The current study evaluated an approach to public-private partnership where corporate volunteers give technical assistance to improve organizational and staff performance. From 2003 to 2005, the Pfizer Global Health Fellows program sent 72 employees to work with organizations in 19 countries. This evaluation was designed to assess program impact. The researchers administered a survey to 60 Fellows and 48 Pfizer Supervisors. In addition, the team conducted over 100 interviews with partner organization staff and other key informants during site visits in Uganda, Kenya, Ghana, South Africa and India, the five countries where 60% of Fellows were placed. Over three-quarters of Fellowships appear to have imparted skills or enhanced operations of NGOs in HIV/AIDS and other health programs. Overall, 79% of Fellows reported meeting all or most technical assistance goals. Partner organization staff reported that the Fellows provided training to clinical and research personnel; strengthened laboratory, pharmacy, financial control, and human resource management systems; and helped expand Partner organization networks. Local staff also reported the Program changed their work habits and attitudes. The evaluation identified problems in defining goals of Fellowships and matching Organizations with Fellows. Capacity building success also appears related to size and sophistication of partner organization. Public expectations have grown regarding the role corporations should play in improving health systems in developing countries. Corporate philanthropy programs based on "donations" of personnel can help build the organizational and human capacity of frontline agencies

  8. The effect of dimerizing domains and basic residues on in vitro and in vivo assembly of Mason-Pfizer monkey virus and Human immunodeficiency virus

    Czech Academy of Sciences Publication Activity Database

    Böhmová, Karolína; Hadravová, Romana; Štokrová, Jitka; Tůma, R.; Ruml, T.; Pichová, Iva; Rumlová, Michaela

    2010-01-01

    Roč. 84, č. 4 (2010), s. 1977-1988 ISSN 0022-538X R&D Projects: GA MŠk 1M0508; GA ČR GA204/09/1388 Grant - others:EUROCORES(XE) ERAS-CT-2003-980409 Institutional research plan: CEZ:AV0Z40550506 Keywords : Mason-Pfizer Monkey Virus * Human Immunodeficiency Virus * assembly * NC Subject RIV: CC - Organic Chemistry Impact factor: 5.189, year: 2010

  9. Specific in vitro cleavage of Mason-Pfizer monkey virus capsid protein: evidence for a potential role of retroviral protease in early stages of infection

    International Nuclear Information System (INIS)

    Rumlova, Michaela; Ruml, Tomas; Pohl, Jan; Pichova, Iva

    2003-01-01

    Processing of Gag polyproteins by viral protease (PR) leads to reorganization of immature retroviral particles and formation of a ribonucleoprotein core. In some retroviruses, such as HIV and RSV, cleavage of a spacer peptide separating capsid and nucleocapsid proteins is essential for the core formation. We show here that no similar spacer peptide is present in the capsid-nucleocapsid (CA-NC) region of Mason-Pfizer monkey virus (M-PMV) and that the CA protein is cleaved in vitro by the PR within the major homology region (MHR) and the NC protein in several sites at the N-terminus. The CA cleavage product was also identified shortly after penetration of M-PMV into COS cells, suggesting that the protease-catalyzed cleavage is involved in core disintegration

  10. Sequences within both the 5' untranslated region and the Gag gene are important for efficient encapsidation of Mason-Pfizer monkey virus RNA

    International Nuclear Information System (INIS)

    Schmidt, Russell D.; Mustafa, Farah; Lew, Kathy A.; Browning, Mathew T.; Rizvi, Tahir A.

    2003-01-01

    It has previously been shown that the 5' untranslated leader region (UTR), including about 495 bp of the gag gene, is sufficient for the efficient encapsidation and propagation of Mason-Pfizer monkey virus (MPMV) based retroviral vectors. In addition, a deletion upstream of the major splice donor, SD, has been shown to adversely affect MPMV RNA packaging. However, the precise sequence requirement for the encapsidation of MPMV genomic RNA within the 5' UTR and gag remains largely unknown. In this study, we have used a systematic deletion analysis of the 5' UTR and gag gene to define the cis-acting sequences responsible for efficient MPMV RNA packaging. Using an in vivo packaging and transduction assay, our results reveal that the MPMV packaging signal is primarily found within the first 30 bp immediately downstream of the primer binding site. However, its function is dependent upon the presence of the last 23 bp of the 5' UTR and approximately the first 100 bp of the gag gene. Thus, sequences that affect MPMV RNA packaging seem to reside both upstream and downstream of the major splice donor with the downstream region responsible for the efficient functioning of the upstream primary packaging determinant

  11. The structure of myristoylated Mason-Pfizer monkey virus matrix protein and the role of phosphatidylinositol-(4,5)-bisphosphate in its membrane binding.

    Science.gov (United States)

    Prchal, Jan; Srb, Pavel; Hunter, Eric; Ruml, Tomáš; Hrabal, Richard

    2012-10-26

    We determined the solution structure of myristoylated Mason-Pfizer monkey virus matrix protein by NMR spectroscopy. The myristoyl group is buried inside the protein and causes a slight reorientation of the helices. This reorientation leads to the creation of a binding site for phosphatidylinositols. The interaction between the matrix protein and phosphatidylinositols carrying C(8) fatty acid chains was monitored by observation of concentration-dependent chemical shift changes of the affected amino acid residues, a saturation transfer difference experiment and changes in (31)P chemical shifts. No differences in the binding mode or affinity were observed with differently phosphorylated phosphatidylinositols. The structure of the matrix protein-phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P(2)] complex was then calculated with HADDOCK software based on the intermolecular nuclear Overhauser enhancement contacts between the ligand and the matrix protein obtained from a (13)C-filtered/(13)C-edited nuclear Overhauser enhancement spectroscopy experiment. PI(4,5)P(2) binding was not strong enough for triggering of the myristoyl-switch. The structural changes of the myristoylated matrix protein were also found to result in a drop in the oligomerization capacity of the protein. Copyright © 2012. Published by Elsevier Ltd.

  12. A G-C-rich palindromic structural motif and a stretch of single-stranded purines are required for optimal packaging of Mason-Pfizer monkey virus (MPMV) genomic RNA.

    Science.gov (United States)

    Jaballah, Soumeya Ali; Aktar, Suriya J; Ali, Jahabar; Phillip, Pretty Susan; Al Dhaheri, Noura Salem; Jabeen, Aayesha; Rizvi, Tahir A

    2010-09-03

    During retroviral RNA packaging, two copies of genomic RNA are preferentially packaged into the budding virus particles whereas the spliced viral RNAs and the cellular RNAs are excluded during this process. Specificity towards retroviral RNA packaging is dependent upon sequences at the 5' end of the viral genome, which at times extend into Gag sequences. It has earlier been suggested that the Mason-Pfizer monkey virus (MPMV) contains packaging sequences within the 5' untranslated region (UTR) and Gag. These studies have also suggested that the packaging determinants of MPMV that lie in the UTR are bipartite and are divided into two regions both upstream and downstream of the major splice donor. However, the precise boundaries of these discontinuous regions within the UTR and the role of the intervening sequences between these dipartite sequences towards MPMV packaging have not been investigated. Employing a combination of genetic and structural prediction analyses, we have shown that region "A", immediately downstream of the primer binding site, is composed of 50 nt, whereas region "B" is composed of the last 23 nt of UTR, and the intervening 55 nt between these two discontinuous regions do not contribute towards MPMV RNA packaging. In addition, we have identified a 14-nt G-C-rich palindromic sequence (with 100% autocomplementarity) within region A that has been predicted to fold into a structural motif and is essential for optimal MPMV RNA packaging. Furthermore, we have also identified a stretch of single-stranded purines (ssPurines) within the UTR and 8 nt of these ssPurines are duplicated in region B. The native ssPurines or its repeat in region B when predicted to refold as ssPurines has been shown to be essential for RNA packaging, possibly functioning as a potential nucleocapsid binding site. Findings from this study should enhance our understanding of the steps involved in MPMV replication including RNA encapsidation process. Copyright (c) 2010 Elsevier Ltd

  13. Baseline characteristics and response to 2 years of growth hormone (GH) replacement of hypopituitary patients with GH deficiency due to adult-onset craniopharyngioma in comparison with patients with nonfunctioning pituitary adenoma: data from KIMS (Pfizer International Metabolic Database).

    Science.gov (United States)

    Verhelst, Johan; Kendall-Taylor, Pat; Erfurth, Eva Marie; Price, David Anthony; Geffner, Mitchell; Koltowska-Häggström, Maria; Jönsson, Peter J; Wilton, Patrick; Abs, Roger

    2005-08-01

    In epidemiological studies, hypopituitary adults show increased mortality compared with population controls. Patients with hypopituitarism caused by a craniopharyngioma (CP) and/or its treatment have a higher mortality than patients with other etiologies, such as a nonfunctioning pituitary adenoma (NFPA). To analyze this difference, we used the KIMS database (Pfizer International Metabolic Database) comparing CP and NFPA patients in terms of baseline characteristics and responses to GH replacement. Baseline characteristics were studied in 351 CP patients (189 men and 162 women; mean age, 42.5 yr) and compared with 370 NFPA patients, matched for age and sex (185 men and 185 women; mean age, 42.5 yr). The effects of 2 yr of GH replacement were analyzed in a subgroup of 183 CP and 209 NFPA patients. At baseline, both CP and NFPA patients had characteristic features of GH deficiency, with low serum IGF-I, increased body fat, dyslipidemia, and reduced quality of life. Male CP patients were significantly more obese (30.0 vs. 28.2 kg/m2; P = 0.0003) compared with NFPA patients, had a higher waist/hip ratio (P = 0.004), higher triglycerides (P = 0.003), and lower high-density lipoprotein cholesterol (P = 0.03). Similar, but much smaller, differences were seen in female CP compared with NFPA patients, only reaching significance for waist/hip ratio (P = 0.05) and triglycerides (P = 0.0004). CP patients had more often undergone surgery by the transcranial route (68.8% vs. 30.9%; P NFPA patients (58.7% vs. 19.8%; P NFPA patients. After 2 yr of GH replacement therapy, similar significant improvements were evident in both groups in fat-free mass, total and low-density lipoprotein cholesterol, and Quality-of-Life-Assessment in GH Deficient Adults score compared with baseline. In contrast to NFPA patients, CP patients had no significant decrease in body fat with GH therapy. In the KIMS database, patients with CP have more often undergone surgery by the transcranial route than

  14. Pfizer's Centers for Therapeutic Innovation (CTI) for NIH Researchers

    Data.gov (United States)

    Federal Laboratory Consortium — NCATS works to make the translational process more efficient and effective by establishing new collaborative partnerships and creating technologies and methods that...

  15. Application of PBPK modelling in drug discovery and development at Pfizer.

    Science.gov (United States)

    Jones, Hannah M; Dickins, Maurice; Youdim, Kuresh; Gosset, James R; Attkins, Neil J; Hay, Tanya L; Gurrell, Ian K; Logan, Y Raj; Bungay, Peter J; Jones, Barry C; Gardner, Iain B

    2012-01-01

    Early prediction of human pharmacokinetics (PK) and drug-drug interactions (DDI) in drug discovery and development allows for more informed decision making. Physiologically based pharmacokinetic (PBPK) modelling can be used to answer a number of questions throughout the process of drug discovery and development and is thus becoming a very popular tool. PBPK models provide the opportunity to integrate key input parameters from different sources to not only estimate PK parameters and plasma concentration-time profiles, but also to gain mechanistic insight into compound properties. Using examples from the literature and our own company, we have shown how PBPK techniques can be utilized through the stages of drug discovery and development to increase efficiency, reduce the need for animal studies, replace clinical trials and to increase PK understanding. Given the mechanistic nature of these models, the future use of PBPK modelling in drug discovery and development is promising, however, some limitations need to be addressed to realize its application and utility more broadly.

  16. Retrovirus D/New England and its relation to Mason-Pfizer monkey virus.

    OpenAIRE

    Desrosiers, R C; Daniel, M D; Butler, C V; Schmidt, D K; Letvin, N L; Hunt, R D; King, N W; Barker, C S; Hunter, E

    1985-01-01

    Seventeen isolates of retrovirus D/New England have been obtained from three species of macaques at the New England Regional Primate Research Center. Seven of the isolates were obtained from macaques who subsequently died with the macaque immunodeficiency syndrome; other isolates were obtained from macaques with less severe or other forms of illness. Attempts to isolate type D retrovirus from peripheral lymphocytes of 97 apparently healthy macaques have not been successful. Cloned DNA was pre...

  17. Paradise profits : tax planning in multinational companies : a case study of Pfizer Inc.

    OpenAIRE

    Evensen, Håvard Skolseg; Nøstvik, Alexander Nymgaard

    2017-01-01

    In recent years, it has become increasingly evident that current tax regulations are not properly equipped to handle the business structures of multinational companies. A number of revelations and leakages have exposed how such companies, often from the US, make use of tax minimization strategies in order to shift profits and reduce tax liabilities. In this thesis, we examine the inner workings of these arrangements, and analyze the extent of aggressive tax planning in the phar...

  18. Structural study of the capsid protein of Mason-Pfizer monkey virus

    Czech Academy of Sciences Publication Activity Database

    Benedíková, Jitka; Pichová, Iva; Ruml, T.; Rumlová, Michaela

    2000-01-01

    Roč. 94, č. 8 (2000), s. 522 ISSN 0009-2770. [Biochemický sjezd /17./. 07.09.2000-10.09.2000, Praha] R&D Projects: GA ČR GA203/00/1005; GA ČR GA203/98/P151 Institutional research plan: CEZ:AV0Z4055905 Subject RIV: CE - Biochemistry

  19. NMR structural studies of proteins from Mason-Pfizer monkey virus

    Czech Academy of Sciences Publication Activity Database

    Hrabal, R.; Veverka, V.; Lang, J.; Bauerová, Helena; Pichová, Iva; Lipov, J.; Ruml, T.

    2002-01-01

    Roč. 9, č. 1 (2002), s. 38-39 ISSN 1211-5894. [Meeting of the Czech and Slovak Structural Biologists /2./. 13.03.2003-15.03.2003, Nové Hrady] Institutional research plan: CEZ:AV0Z4055905 Keywords : M-PMV Subject RIV: CE - Biochemistry

  20. Nucleic Acid Binding by Mason-Pfizer Monkey Virus CA Promotes Virus Assembly and Genome Packaging

    Czech Academy of Sciences Publication Activity Database

    Füzik, T.; Píchalová, R.; Schur, F. K. M.; Strohalmová, Karolína; Křížová, Ivana; Hadravová, Romana; Rumlová, Michaela; Briggs, J. A. G.; Ulbrich, P.; Ruml, T.

    2016-01-01

    Roč. 90, č. 9 (2016), s. 4593-4603 ISSN 0022-538X R&D Projects: GA ČR(CZ) GA14-15326S; GA MŠk LO1302; GA MŠk(CZ) LO1304 Institutional support: RVO:61388963 Keywords : M-PMV * virus assembly * capsid protein Subject RIV: EE - Microbiology, Virology Impact factor: 4.663, year: 2016

  1. Breast cancer-associated protein - a novel binding partner of Mason-Pfizer monkey virus protease

    Czech Academy of Sciences Publication Activity Database

    Rumlová, Michaela; Křížová, Ivana; Hadravová, Romana; Doležal, Michal; Strohalmová, Karolína; Keprová, Alena; Pichová, Iva; Ruml, T.

    2014-01-01

    Roč. 95, č. 6 (2014), s. 1383-1389 ISSN 0022-1317 R&D Projects: GA ČR GA204/09/1388 Institutional support: RVO:61388963 Keywords : gene * AKIP1 * expression Subject RIV: EE - Microbiology, Virology Impact factor: 3.183, year: 2014

  2. WAAVP/Pfizer award for excellence in teaching veterinary parasitology: teaching of veterinary parasitology--quo vadis?

    Science.gov (United States)

    Eckert, J

    2000-02-29

    Some thoughts on training and recruitment of academic teachers and future trends in teaching veterinary parasitology are presented with emphasis on the European situation. It is underlined that research is an indispensable basis for academic teaching. Besides a broad scientific background of the teacher, motivation and teaching methods are also important. Many academic teachers do not receive formal training in teaching methods. In order to improve future education, training of staff members in teaching methods should be promoted. Quality control of teaching and research, already established in many schools, should generally be introduced. Teaching is mostly underestimated in relation to research. Therefore, more weight should be placed on the former both in selecting scientists for the career as academic teachers and in evaluating and ranking departments for their academic activities. In the future veterinary medicine will have to cope with profound changes in the society and the veterinary profession, and the progressing European unification will enhance trends for internationalizing teaching curricula. Therefore, veterinary medicine has to reconsider the teaching subjects and methods and to lay more emphasis on flexibility, skills of problem-solving and self-learning and on training for life-long learning. At present there is an ongoing discussion on the question how to teach veterinary medicine, including veterinary parasitology. There are various options, and some of them are discussed, namely, the disciplinary and the problem-based/organ-focussed approaches. It is concluded that for teaching of veterinary parasitology and related disciplines a combined disciplinary and problem-based approach offers the best chances for fulfilling the requirements of teaching for the future. In the curriculum of undergraduate teaching of veterinary medicine at least 70-90 h should be dedicated to veterinary parasitology using a disciplinary and taxonomic approach. Additional hours are required for instructions on clinical cases in approaches focussed on animal species and/or organ diseases. As there is a need for discussing teaching issues, post-graduate specialization, and continuing education in parasitology and related disciplines on national and international levels, it is recommended to WAAVP to include regular workshops on teaching in the programmes of the biannual conferences, and to establish a permanent committee which should collect information and submit proposals for improvement of teaching veterinary parasitology.

  3. Multimerization of the p12 domain is necessary for Mason–Pfizer monkey virus Gag assembly in vitro

    Czech Academy of Sciences Publication Activity Database

    Knejzlík, Z.; Smékalová, Z.; Ruml, Tomáš; Sakalian, M.

    2007-01-01

    Roč. 365, č. 2 (2007), s. 260-270 ISSN 0042-6822 R&D Projects: GA MŠk(CZ) 1M0520; GA ČR GESCO/06/E001 Grant - others:NIH(US) AI43230 Institutional research plan: CEZ:AV0Z40550506 Keywords : M-PMV * p12 protein * oligomerization * leucine zipper Subject RIV: CE - Biochemistry Impact factor: 3.765, year: 2007

  4. The impact of altered polyprotein ratios on the assembly and infectivity of Mason-Pfizer monkey virus

    Czech Academy of Sciences Publication Activity Database

    Kohoutová, Z.; Rumlová, Michaela; Andreánský, M.; Sakalian, M.; Hunter, E.; Pichová, Iva; Ruml, T.

    2009-01-01

    Roč. 384, č. 1 (2009), s. 59-68 ISSN 0042-6822 R&D Projects: GA MŠk 1M0508; GA AV ČR KAN200100801; GA ČR GESCO/06/E001 Grant - others:GA MŠk(CZ) 1M0520; GA AV ČR(CZ) KAN208240651 Program:1M Institutional research plan: CEZ:AV0Z40550506 Keywords : retrovirus * assembly * frameshift * infectivity Subject RIV: CE - Biochemistry Impact factor: 3.042, year: 2009

  5. Conformational changes of the N-terminal part of Mason-Pfizer monkey virus p12 protein during multimerization

    Czech Academy of Sciences Publication Activity Database

    Knejzlík, Z.; Ulbrich, P.; Strohalm, Martin; Laštůvková, H.; Kodíček, M.; Sakalian, M.; Ruml, T.

    2009-01-01

    Roč. 393, č. 1 (2009), s. 168-176 ISSN 0042-6822 Institutional research plan: CEZ:AV0Z50200510 Keywords : alpha-Helix * Multimerization * CD spectroscopy Subject RIV: EE - Microbiology, Virology Impact factor: 3.042, year: 2009

  6. NMR structure of the N-terminal domain of capsid protein from the Mason-Pfizer monkey virus

    Czech Academy of Sciences Publication Activity Database

    Macek, Pavel; Chmelík, Josef; Křížová, Ivana; Kadeřávek, P.; Padrta, P.; Žídek, L.; Wildová, Marcela; Hadravová, Romana; Chaloupková, R.; Pichová, Iva; Ruml, T.; Rumlová, Michaela; Sklenář, V.

    2009-01-01

    Roč. 392, č. 1 (2009), s. 100-114 ISSN 0022-2836 R&D Projects: GA MŠk LC545; GA MŠk 1M0508; GA ČR GA204/09/1388; GA ČR GESCO/06/E001 Grant - others:GA MŠk(CZ) 1M0520; MŠk(CZ) LC06030 Program:1M; LC Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50200510 Keywords : M-PMV * betaretroviruses * capsid protein * NMR structure * internal dynamics Subject RIV: CE - Biochemistry Impact factor: 3.871, year: 2009

  7. Molecular aspects of the interaction between MasonPfizer monkey virus matrix protein and artificial phospholipid membrane

    Czech Academy of Sciences Publication Activity Database

    Junková, P.; Prchal, J.; Spiwok, V.; Pleskot, Roman; Kadlec, J.; Krásný, Libor; Hynek, R.; Hrabal, R.; Ruml, T.

    2016-01-01

    Roč. 84, č. 11 (2016), s. 1717-1727 ISSN 0887-3585 Institutional support: RVO:61389030 ; RVO:61388971 Keywords : d-type retrovirus * force-field * nucleotide-sequence * myristate exposure * plasma-membrane * rhesus monkey Subject RIV: EB - Genetics ; Molecular Biology; EE - Microbiology, Virology (MBU-M) Impact factor: 2.289, year: 2016

  8. Structural and dynamic studies of the 12 kDa form of protease from Mason-Pfizer monkey virus

    Czech Academy of Sciences Publication Activity Database

    Veverka, V.; Lang, J.; Bauerová, Helena; Pichová, Iva; Hrabal, R.

    2003-01-01

    Roč. 10, č. 1 (2003), s. 40 ISSN 1211-5894. [Meeting of the Czech and Slovak Structural Biologists /2./. 13.03.2002-15.03.2002, Nové Hrady] R&D Projects: GA ČR GA203/00/1241 Institutional research plan: CEZ:AV0Z4055905 Keywords : M-PMV PR Subject RIV: CE - Biochemistry

  9. Stabilization of the beta-hairpin in Mason-Pfizer monkey virus capsid protein- a critical step for infectivity

    Czech Academy of Sciences Publication Activity Database

    Obr, M.; Hadravová, Romana; Doležal, Michal; Křížová, Ivana; Papoušková, V.; Žídek, L.; Hrabal, R.; Ruml, T.; Rumlová, Michaela

    2014-01-01

    Roč. 11, Oct 30 (2014), 94/1-94/14 ISSN 1742-4690 R&D Projects: GA ČR(CZ) GA14-15326S; GA MŠk LO1302 Grant - others:GA MŠk(CZ) ED1.1.00/02.0068; Seventh Framework Programme of the European Union(XE) FP7-261863 Program:ED Institutional support: RVO:61388963 Keywords : retrovirus * assembly * M-PMV * capsid protein * maturation * beta-hairpin Subject RIV: EE - Microbiology, Virology Impact factor: 4.185, year: 2014 http://www.retrovirology.com/content/11/1/94

  10. Distinct roles for nucleic acid in vitro assembly of purified Mason-Pfizer monkey virus CANC proteins

    Czech Academy of Sciences Publication Activity Database

    Ulbrich, P.; Haubová, Š.; Nermut, M. V.; Hunter, E.; Rumlová, Michaela; Ruml, Tomáš

    2006-01-01

    Roč. 80, č. 14 (2006), s. 7089-7099 ISSN 0022-538X R&D Projects: GA AV ČR(CZ) IAA4055304; GA ČR(CZ) GP203/03/P094; GA MŠk 1M0520 Institutional research plan: CEZ:AV0Z40550506 Keywords : M-PMV * CANC proteins * HIV-1 * in vitro assembly Subject RIV: CE - Biochemistry Impact factor: 5.341, year: 2006

  11. Atomic Force microscopy investigation of Mason-Pfizer monkey virus and human immunodeficiency virus type 1 reassembled particles

    Czech Academy of Sciences Publication Activity Database

    Kuznetsov, Y.G.; Ulbrich, Pavel; Haubová, Š.; Ruml, Tomáš; McPherson, A.

    2007-01-01

    Roč. 360, č. 2 (2007), s. 434-446 ISSN 0042-6822 R&D Projects: GA MŠk(CZ) 1M0520 Grant - others:NIH(US) GM58868; GA MZd(CZ) NR8797 Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z40550506 Keywords : Retrovirus * Capsid * Architecture Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.765, year: 2007

  12. The G-Patch Domain of Mason-Pfizer Monkey Virus Is a Part of Reverse Transcriptase

    Czech Academy of Sciences Publication Activity Database

    Křížová, Ivana; Hadravová, Romana; Štokrová, Jitka; Günterová, Jana; Doležal, Michal; Ruml, T.; Rumlová, Michaela; Pichová, Iva

    2012-01-01

    Roč. 68, č. 4 (2012), s. 1988-1998 ISSN 0022-538X R&D Projects: GA MŠk 1M0508; GA ČR GA204/09/1388 Grant - others:GA MŠk(CZ) ME 904 Institutional research plan: CEZ:AV0Z40550506 Keywords : DNA repair enzyme * retroviral protease * Toxoplasma gondii * leukemia-virus * containing RNA Subject RIV: CE - Biochemistry Impact factor: 5.076, year: 2012

  13. Molecular aspects of the interaction between Mason-Pfizer monkey virus matrix protein and artificial phospholipid membrane

    Czech Academy of Sciences Publication Activity Database

    Junková, P.; Prchal, J.; Spiwok, V.; Pleskot, Roman; Kadlec, Jan; Krásný, L.; Hynek, R.; Hrabal, R.; Ruml, T.

    2016-01-01

    Roč. 84, č. 11 (2016), s. 1717-1727 ISSN 0887-3585 Institutional support: RVO:61388963 Keywords : covalent labelling * mass spectrometry * multiscale molecular dynamics * protein-membrane interaction * phosphatidylinositol-(4,5)-bisphosphate * liposomes Subject RIV: CE - Biochemistry Impact factor: 2.289, year: 2016

  14. Role of Mason-Pfizer Monkey Virus CA-NC Spacer Peptide-Like Domain in Assembly of Immature Particles

    Czech Academy of Sciences Publication Activity Database

    Strohalmová-Böhmová, Karolína; Spiwok, V.; Lepšík, Martin; Hadravová, Romana; Křížová, Ivana; Ulbrich, P.; Pichová, Iva; Bednárová, Lucie; Ruml, T.; Rumlová, Michaela

    2014-01-01

    Roč. 88, č. 24 (2014), s. 14148-14160 ISSN 0022-538X R&D Projects: GA ČR(CZ) GA14-15326S; GA MŠk LO1302; GA ČR GBP208/12/G016 Institutional support: RVO:61388963 Keywords : human immunodeficiency virus * HIV-1 capsid protein * murine leukemia virus Subject RIV: EE - Microbiology, Virology Impact factor: 4.439, year: 2014

  15. An economic model of long-term use of celecoxib in patients with osteoarthritis

    Directory of Open Access Journals (Sweden)

    Rublee Dale

    2007-07-01

    Full Text Available Abstract Background Previous evaluations of the cost-effectiveness of the cyclooxygenase-2 selective inhibitor celecoxib (Celebrex, Pfizer Inc, USA have produced conflicting results. The recent controversy over the cardiovascular (CV risks of rofecoxib and other coxibs has renewed interest in the economic profile of celecoxib, the only coxib now available in the United States. The objective of our study was to evaluate the long-term cost-effectiveness of celecoxib compared with nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs in a population of 60-year-old osteoarthritis (OA patients with average risks of upper gastrointestinal (UGI complications who require chronic daily NSAID therapy. Methods We used decision analysis based on data from the literature to evaluate cost-effectiveness from a modified societal perspective over patients' lifetimes, with outcomes expressed as incremental costs per quality-adjusted life-year (QALY gained. Sensitivity tests were performed to evaluate the impacts of advancing age, CV thromboembolic event risk, different analytic horizons and alternate treatment strategies after UGI adverse events. Results Our main findings were: 1 the base model incremental cost-effectiveness ratio (ICER for celecoxib versus nsNSAIDs was $31,097 per QALY; 2 the ICER per QALY was $19,309 for a model in which UGI ulcer and ulcer complication event risks increased with advancing age; 3 the ICER per QALY was $17,120 in sensitivity analyses combining serious CV thromboembolic event (myocardial infarction, stroke, CV death risks with base model assumptions. Conclusion Our model suggests that chronic celecoxib is cost-effective versus nsNSAIDs in a population of 60-year-old OA patients with average risks of UGI events.

  16. Packaging of Mason-Pfizer monkey virus (MPMV) genomic RNA depends upon conserved long-range interactions (LRIs) between U5 and gag sequences.

    Science.gov (United States)

    Kalloush, Rawan M; Vivet-Boudou, Valérie; Ali, Lizna M; Mustafa, Farah; Marquet, Roland; Rizvi, Tahir A

    2016-06-01

    MPMV has great potential for development as a vector for gene therapy. In this respect, precisely defining the sequences and structural motifs that are important for dimerization and packaging of its genomic RNA (gRNA) are of utmost importance. A distinguishing feature of the MPMV gRNA packaging signal is two phylogenetically conserved long-range interactions (LRIs) between U5 and gag complementary sequences, LRI-I and LRI-II. To test their biological significance in the MPMV life cycle, we introduced mutations into these structural motifs and tested their effects on MPMV gRNA packaging and propagation. Furthermore, we probed the structure of key mutants using SHAPE (selective 2'hydroxyl acylation analyzed by primer extension). Disrupting base-pairing of the LRIs affected gRNA packaging and propagation, demonstrating their significance to the MPMV life cycle. A double mutant restoring a heterologous LRI-I was fully functional, whereas a similar LRI-II mutant failed to restore gRNA packaging and propagation. These results demonstrate that while LRI-I acts at the structural level, maintaining base-pairing is not sufficient for LRI-II function. In addition, in vitro RNA dimerization assays indicated that the loss of RNA packaging in LRI mutants could not be attributed to the defects in dimerization. Our findings suggest that U5-gag LRIs play an important architectural role in maintaining the structure of the 5' region of the MPMV gRNA, expanding the crucial role of LRIs to the nonlentiviral group of retroviruses. © 2016 Kalloush et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  17. 1H, 13C, and 15N resonance assignment of the N-terminal domainof Mason-Pfizer monkey virus capsid protein, CA 1-140

    Czech Academy of Sciences Publication Activity Database

    Macek, Pavel; Žídek, L.; Rumlová, Michaela; Pichová, Iva; Sklenář, V.

    2008-01-01

    Roč. 2, č. 1 (2008), s. 43-45 ISSN 1874-2718 R&D Projects: GA MŠk LC545; GA MŠk(CZ) LC06030; GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z50200510; CEZ:AV0Z40550506 Keywords : nmr * assignment * capsid protein Subject RIV: EE - Microbiology, Virology Impact factor: 0.015, year: 2008

  18. Resonance assignments of the myristoylated Y28F/Y67F mutant of the Mason-Pfizer monkey virus matrix protein

    Czech Academy of Sciences Publication Activity Database

    Doležal, Michal; Hrabal, R.; Ruml, T.; Rumlová, Michaela

    2015-01-01

    Roč. 9, č. 2 (2015), s. 229-233 ISSN 1874-2718 Institutional support: RVO:61388963 Keywords : isotopic labeling * matrix protein * M-PMV * myristoylation * resonance assignment * reverse labeling Subject RIV: CE - Biochemistry Impact factor: 0.687, year: 2015

  19. The RNA binding G-patch domain in retroviral protease is important for infectivity and D-type morphogenesis of Mason-Pfizer monkey virus

    Czech Academy of Sciences Publication Activity Database

    Bauerová, Helena; Štokrová, Jitka; Stříšovský, Kvido; Hunter, E.; Ruml, Tomáš; Pichová, Iva

    2005-01-01

    Roč. 280, č. 51 (2005), s. 42106-42112 ISSN 0021-9258 R&D Projects: GA MŠk(CZ) 1M0508; GA MŠk(CZ) 1M0520 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50520514 Keywords : retroviral protease * RNA binding domain * M-PMV * infectivity * assembly Subject RIV: CE - Biochemistry Impact factor: 5.854, year: 2005

  20. dUTPase and nucleocapsid polypeptides of the Mason-Pfizer monkey virus form a fusion protein in the virion with homotrimeric organization and low catalytic efficiency

    Czech Academy of Sciences Publication Activity Database

    Barabás, O.; Rumlová, Michaela; Erdei, A.; Pongrácz, V.; Pichová, Iva; Vértessy, B. G.

    2003-01-01

    Roč. 278, č. 40 (2003), s. 38803-38812 ISSN 0021-9258 R&D Projects: GA AV ČR IAA4055304 Grant - others:HNRF(HU) T034120; HNRF(HU) TS044730; HNRF(HU) M27852; HHMI(US) 55000342 Institutional research plan: CEZ:AV0Z4055905 Keywords : dUTPase * M-PMV * pyrophosphatase Subject RIV: CE - Biochemistry Impact factor: 6.482, year: 2003

  1. The effect of point mutations within the N-terminal domain of Mason-Pfizer monkey virus capsid protein on virus core assembly and infectivity

    Czech Academy of Sciences Publication Activity Database

    Wildová, Marcela; Hadravová, Romana; Štokrová, Jitka; Křížová, Ivana; Ruml, Tomáš; Hunter, E.; Pichová, Iva; Rumlová, Michaela

    2008-01-01

    Roč. 380, č. 1 (2008), s. 157-163 ISSN 0042-6822 R&D Projects: GA MŠk 1M0508; GA ČR GESCO/06/E001; GA AV ČR KAN200200651 Grant - others:GA MŠk(CZ) 1M0520 Program:1M Institutional research plan: CEZ:AV0Z40550506 Keywords : caspid protein * assembly * M-PMV Subject RIV: CE - Biochemistry Impact factor: 3.539, year: 2008

  2. Amino acid residues in the cytoplasmic domain of the Mason-Pfizer monkey virus glycoprotein critical for its incorporation into virions

    Czech Academy of Sciences Publication Activity Database

    Song, CH.; Micoli, K.; Bauerová, Helena; Pichová, Iva; Hunter, E.

    2005-01-01

    Roč. 79, č. 18 (2005), s. 11559-11568 ISSN 0022-538X R&D Projects: GA AV ČR(CZ) IAA4055304 Grant - others:NIH(US) CA-27834; NIH(US) P30-AI-27767 Institutional research plan: CEZ:AV0Z40550506 Keywords : M-PMV * Env * infectivity Subject RIV: CE - Biochemistry Impact factor: 5.178, year: 2005

  3. Specific in vitro cleavage of Mason-Pfizer monkey virus capsid protein: evidence for a potential role of retroviral protease in early stages of infection

    Czech Academy of Sciences Publication Activity Database

    Rumlová, Michaela; Ruml, T.; Pohl, J.; Pichová, Iva

    2003-01-01

    Roč. 310, - (2003), s. 310-318 ISSN 0042-6822 R&D Projects: GA ČR GA203/00/1241; GA AV ČR IAB4055202 Institutional research plan: CEZ:AV0Z4055905 Keywords : M-PMV protease * HIV-1 capsid protein * HIV-1 protease Subject RIV: CE - Biochemistry Impact factor: 3.391, year: 2003

  4. How direct-to-consumer television advertising for osteoarthritis drugs affects physicians' prescribing behavior.

    Science.gov (United States)

    Bradford, W David; Kleit, Andrew N; Nietert, Paul J; Steyer, Terrence; McIlwain, Thomas; Ornstein, Steven

    2006-01-01

    Concern about the potential pernicious effect of direct-to-consumer (DTC) drug advertising on physicians' prescribing patterns was heightened with the 2004 withdrawal of Vioxx, a heavily advertised treatment for osteoarthritis. We examine how DTC advertising has affected physicians' prescribing behavior for osteoarthritis patients. We analyzed monthly clinical information on fifty-seven primary care practices during 2000-2002, matched to monthly brand-specific advertising data for local and network television. DTC advertising of Vioxx and Celebrex increased the number of osteoarthritis patients seen by physicians each month. DTC advertising of Vioxx increased the likelihood that patients received both Vioxx and Celebrex, but Celebrex ads only affected Vioxx use.

  5. NCBI nr-aa BLAST: CBRC-STRI-01-2068 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-STRI-01-2068 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 1e-160 49% ...

  6. NCBI nr-aa BLAST: CBRC-EEUR-01-1301 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-EEUR-01-1301 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 4e-84 40% ...

  7. NCBI nr-aa BLAST: CBRC-MMUR-01-1147 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MMUR-01-1147 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 0.0 54% ...

  8. NCBI nr-aa BLAST: CBRC-DNOV-01-1417 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DNOV-01-1417 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 0.0 64% ...

  9. NCBI nr-aa BLAST: CBRC-RNOR-01-0383 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-RNOR-01-0383 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 1e-142 46% ...

  10. NCBI nr-aa BLAST: CBRC-OPRI-01-1148 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OPRI-01-1148 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 0.0 53% ...

  11. NCBI nr-aa BLAST: CBRC-DNOV-01-1613 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DNOV-01-1613 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 0.0 62% ...

  12. NCBI nr-aa BLAST: CBRC-MMUR-01-1306 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MMUR-01-1306 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 0.0 56% ...

  13. NCBI nr-aa BLAST: CBRC-OPRI-01-1365 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OPRI-01-1365 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 7e-88 53% ...

  14. NCBI nr-aa BLAST: CBRC-STRI-01-0672 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-STRI-01-0672 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 1e-161 48% ...

  15. NCBI nr-aa BLAST: CBRC-DNOV-01-1718 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DNOV-01-1718 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 1e-170 61% ...

  16. NCBI nr-aa BLAST: CBRC-OPRI-01-0597 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OPRI-01-0597 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 0.0 54% ...

  17. NCBI nr-aa BLAST: CBRC-DNOV-01-2337 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DNOV-01-2337 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 0.0 57% ...

  18. NCBI nr-aa BLAST: CBRC-STRI-01-2886 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-STRI-01-2886 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 1e-162 46% ...

  19. NCBI nr-aa BLAST: CBRC-OPRI-01-0847 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OPRI-01-0847 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 0.0 54% ...

  20. NCBI nr-aa BLAST: CBRC-STRI-01-1568 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-STRI-01-1568 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 3e-75 47% ...

  1. NCBI nr-aa BLAST: CBRC-DNOV-01-2594 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DNOV-01-2594 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 1e-132 58% ...

  2. NCBI nr-aa BLAST: CBRC-OPRI-01-0267 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OPRI-01-0267 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 1e-148 50% ...

  3. NCBI nr-aa BLAST: CBRC-OPRI-01-1340 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OPRI-01-1340 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 1e-128 49% ...

  4. NCBI nr-aa BLAST: CBRC-DNOV-01-2785 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DNOV-01-2785 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 0.0 63% ...

  5. NCBI nr-aa BLAST: CBRC-MMUR-01-1408 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MMUR-01-1408 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 0.0 53% ...

  6. NCBI nr-aa BLAST: CBRC-OPRI-01-0523 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OPRI-01-0523 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 1e-162 49% ...

  7. NCBI nr-aa BLAST: CBRC-CPOR-01-1647 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-CPOR-01-1647 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 0.0 60% ...

  8. NCBI nr-aa BLAST: CBRC-STRI-01-0732 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-STRI-01-0732 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 1e-167 47% ...

  9. NCBI nr-aa BLAST: CBRC-MMUR-01-0147 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MMUR-01-0147 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 0.0 56% ...

  10. NCBI nr-aa BLAST: CBRC-DNOV-01-0164 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DNOV-01-0164 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 6e-90 34% ...

  11. NCBI nr-aa BLAST: CBRC-MMUR-01-0448 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MMUR-01-0448 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 0.0 55% ...

  12. NCBI nr-aa BLAST: CBRC-CPOR-01-0809 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-CPOR-01-0809 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 0.45 28% ...

  13. NCBI nr-aa BLAST: CBRC-OPRI-01-1462 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OPRI-01-1462 ref|NP_056891.1| RT-IN [Mason-Pfizer monkey virus] ref|NP_954565....2| RT-IN [Mason-Pfizer monkey virus] gb|AAC82576.1| RT-IN [Mason-Pfizer monkey virus] NP_056891.1 0.0 54% ...

  14. Modified of an Accepted Animal Model of Osteomyelitis to Simulate and Evaluate Treatment of War Extremity Wounds. Addendum

    Science.gov (United States)

    2012-07-01

    received a probiotic preparation, Probios® powder (KV Vet), 8 g po q24h, in conjunction with nutritional supplements. Weight changes of animals in Groups A...cell Inactivated whole-cell vaccine with proprietary polymer adjuvant or bivalent whole-cell killed Veterinary vaccines for dogs Lipoprotein Lyme

  15. Voriconazole, a safe alternative for treating infections caused by the Chrysosporium anamorph of Nannizziopsis vriesii in bearded dragons (Pogona vitticeps).

    Science.gov (United States)

    Van Waeyenberghe, L; Baert, K; Pasmans, F; van Rooij, P; Hellebuyck, T; Beernaert, L; de Backer, P; Haesebrouck, F; Martel, A

    2010-09-01

    Dermal and systemic infections caused by the Chrysosporium anamorph of Nannizziopsis vriesii (CANV) are highly prevalent in reptiles and may result in severe disease and high mortality. Due to the high incidence of therapeutic failures, optimizing treatment is required. We first determined in this study the minimal inhibitory concentrations (MIC) of itraconazole, voriconazole, amphotericin B and terbinafine against 32 CANV isolates. For voriconazole, amphotericin B and terbinafine a monomodal MIC distribution was seen, whereas a bimodal MIC distribution was present for itraconazole, indicating acquired resistance in one isolate. Fourteen naturally-infected bearded dragons (Pogona vitticeps), from the same owner, were treated orally with either itraconazole (5 mg/kg q24h) or voriconazole (10 mg/kg q24h). The clinical condition, drug plasma concentrations and the presence of CANV in skin samples were followed. The animals were treated until complete clearance of the fungus. The plasma concentrations of voriconazole and itraconazole exceeded the minimal inhibitory concentrations of the CANV isolates. Elimination of CANV was achieved on average after 27 and 47 days of treatment with itraconazole and voriconazole, respectively. Whereas only 2 out of 7 survived after itraconazole treatment, only a single animal died in the voriconazole treated group. In conclusion, based on a limited number of animals, voriconazole applied at a regimen of 10 mg/kg bodyweight (BW) q24h seems to be a safe and effective antimycotic drug to eliminate CANV infections in bearded dragons.

  16. Behavioral Health Needs Assessment Survey (BHNAS): Overview of Survey Items and Measures

    Science.gov (United States)

    2013-02-12

    medication use • Personal and unit morale • Unit cohesion • Attitudes toward leadership • Positive effects of deployment • Navy support during deployment...to select any of the following: • Over-the-counter drugs (including Aspirin, Tylenol, Motrin, Ibuprofen, Aleve) • Prescription painkillers that...are not opioids (including Celebrex, Vioxx, Bextra, topical lidocaine) • Prescription opioid/narcotic painkiller (including OxyContin, Percocet

  17. A Chemopreventive Nanodiamond Platform for Oral Cancer Treatment.

    Science.gov (United States)

    Yen, Albert; Zhang, Kangyi; Daneshgaran, Giulia; Kim, Ho-Joong; Ho, Dean

    2016-02-01

    Standard oral cancer therapy generally includes a combination of surgery with chemotherapy and/or radiotherapy. This treatment paradigm has not changed in some time. In this paper, we propose a chemopreventive nanodiamond platform for the delivery of celecoxib (Celebrex) to oral cancer lesions. This innovative platform allows for sustained drug release under physiological conditions, potentially enhancing chemopreventive efficacy of celecoxib without the physical and toxicological damage associated with conventional means of drug delivery.

  18. Effects of aspirin, carprofen, deracoxib, and meloxicam on platelet function and systemic prostaglandin concentrations in healthy dogs.

    Science.gov (United States)

    Blois, Shauna L; Allen, Dana G; Wood, R Darren; Conlon, Peter D

    2010-03-01

    To determine effects of therapeutic dosages of aspirin, carprofen, deracoxib, and meloxicam on platelet function and systemic prostaglandin concentrations in healthy dogs. 10 hound-crossbred dogs. Aspirin (10 mg/kg, PO, q 12 h), carprofen (4.4 mg/kg, PO, q 24 h), deracoxib (2 mg/kg, PO, q 24 h), meloxicam (0.1 mg/kg, PO, q 24 h), and a placebo were administered for 7 days in a random order to each of 10 healthy dogs; there was a 21-day washout period between subsequent treatments. One-stage prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration, and plasma concentrations of thromboxane (TX)B(2) and 6-keto prostaglandin (PG)F(1alpha) were measured before and after treatment administration. Platelet function was assessed by use of a platelet-function analyzer and aggregation. Aspirin, carprofen, and meloxicam did not significantly affect platelet function. Deracoxib caused a mild decrease in platelet aggregation induced by 50microM ADP. Platelet number, Hct, PT, aPTT, and plasma TXB(2) and 6-keto PGF(1alpha) concentrations were unchanged after NSAID administration. Meloxicam administration resulted in a significant decrease in fibrinogen concentration, but results remained within the laboratory reference interval. Oral administration of commonly used NSAIDs at therapeutic dosages in healthy dogs did not alter plasma TXB(2) and 6-keto PGF(1alpha) concentrations. Deracoxib administration resulted in a minor abnormality in platelet aggregation. Anti-inflammatory doses of aspirin did not affect platelet function as measured by use of optical aggregometry and a platelet-function analyzer. Further evaluation of the effects of aspirin and cyclooxygenase-2-selective inhibitors on hemostasis should be performed.

  19. Technical Assessment: Synthetic Biology

    Science.gov (United States)

    2015-01-01

    Pfizer, Bausch & Lomb, Coca - Cola , and other Fortune 500 companies 8 Data estimated by the... financial prize for ideas to drive forward the production of a sensor relying on synthetic organisms that can detect exposure to 500 specific chemicals

  20. 76 FR 49649 - Oral Dosage Form New Animal Drugs; Change of Sponsor; Chlortetracycline; Sulfamethazine

    Science.gov (United States)

    2011-08-11

    ... of Pfizer, Inc., to Boehringer Ingelheim Vetmedica, Inc. DATES: This rule is effective August 11...-018, 055-039, 065-071, and 065-440) to Boehringer Ingelheim Vetmedica, Inc., 2621 North Belt Highway...

  1. Marketingový mix ve farmaceutické společnosti

    OpenAIRE

    Marešová, Markéta

    2009-01-01

    This thesis deals with describing marketing mix of pharmaceutical company. Describes the different parts of the marketing mix of Pfizer. Next, I focused on a specific product of this company - multivitamins Centrum.

  2. 75 FR 14444 - Determination That DIDREX (Benzphetamine Hydrochloride) Tablets, 25 Milligrams, Were Not...

    Science.gov (United States)

    2010-03-25

    ... subsidiary of Pfizer Inc. Benzphetamine HCl 25-mg tablets are indicated in the management of exogenous obesity as a short-term (a few weeks) adjunct in a regimen of weight reduction based on caloric...

  3. Registered nurses' (RNS) perception of the nursing profession and ...

    African Journals Online (AJOL)

    Background A healthy work environment has tremendous benefits on ... by Pfizer to measure Nurses expectations and needs in a 2009 ICN Quadrennial Study. ... 75(45.5%) and an environment of team work and collegiality 71(43.0%).

  4. 2125-IJBCS-Article-Ayakanmi Adekunle Dada

    African Journals Online (AJOL)

    hp

    Use of fluted pumpkin (Telfairia occidentalis) leaf powder as feed additive in. African catfish ... in fish to replace antibiotic growth promoters. .... Vitamin premix – A Pfizer livestock product containing the following per kg of feed: A = 4500 I. U,.

  5. Presidential Green Chemistry Challenge: 2002 Greener Synthetic Pathways Award

    Science.gov (United States)

    Presidential Green Chemistry Challenge 2002 award winner, Pfizer, improved its synthesis of sertraline, the active ingredient in its drug, Zoloft, to double the yield and reduce the use of raw materials, energy, and water.

  6. Viagra warning re "poppers" and notice re protease inhibitors.

    Science.gov (United States)

    James, J S

    1998-05-01

    Pfizer, Inc., manufacturer of Viagra (sildenafil), is warning patients that Viagra is contraindicated with nitrate inhalers (poppers). Nitrates in any form or nitric oxide donors can potentially cause hypotension. Pfizer also recommends that patients using protease inhibitors, particularly ritonavir, use a lower dose of Viagra (25 mg) because they interfere with the elimination of Viagra. This interaction does not pose a significant risk to the patient.

  7. Identification of a potential fibromyalgia diagnosis using random forest modeling applied to electronic medical records

    OpenAIRE

    Masters, Elizabeth T.; Emir,Birol; Mardekian,Jack; Clair,Andrew; Kuhn,Max; Silverman,Stuart

    2015-01-01

    Birol Emir,1 Elizabeth T Masters,1 Jack Mardekian,1 Andrew Clair,1 Max Kuhn,2 Stuart L Silverman,3 1Pfizer Inc., New York, NY, 2Pfizer Inc., Groton, CT, 3Cedars-Sinai Medical Center, Los Angeles, CA, USA Background: Diagnosis of fibromyalgia (FM), a chronic musculoskeletal condition characterized by widespread pain and a constellation of symptoms, remains challenging and is often delayed. Methods: Random forest modeling of electronic medical records was used to identify variables that may fa...

  8. Effect of diet and tylosin on chronic diarrhea in beagles.

    Science.gov (United States)

    Westermarck, Elias; Frias, Rafael; Skrzypczak, Teresa

    2005-01-01

    Seven beagles in a colony of dogs had chronic diarrhea for at least 30 days. The dogs were subsequently treated with tylosin 20 mg/kg BW q24h PO for 10 days. During the treatment period, the feces became firmer but remained loose. When the treatment was discontinued, the diarrhea reappeared in 3 weeks. The feces remained abnormally loose in all dogs treated with metronidazole, trimethoprim-sulfadiazine, or doxycycline and prednisone. The diet was then changed for 10 days from a highly digestible moist pet food to a dry food developed for normal adult dogs. The feces again became firmer, although still loose in some dogs. The period was then extended to 3 month, but the fecal consistency continued to fluctuate from ideal to diarrhea. The dogs were treated a 2nd time with tylosin 20 mg/kg BW q24h PO for 10 days. The feces then became significantly firmer and remained so throughout a 3-month follow-up. We conclude that the combination of diet and tylosin was more effective than either agent alone in control of chronic diarrhea.

  9. Benazepril and subclinical feline hypertrophic cardiomyopathy: A prospective, blinded, controlled study

    Science.gov (United States)

    Di Fruscia, Rocky

    2006-01-01

    Abstract Twenty-one cats with hypertrophic cardiomyopathy were enrolled in this study to determine if the administration of benazepril (0.5 mg/kg body weight [BW], PO, q24h) to cats with subclinical hypertrophic cardiomyopathy improves cardiac diastolic function and reverses left ventricular hypertrophy when compared with diltiazem controlled delivery (CD) (10 mg/kg BW, PO, q24h). Cats were evaluated at day 0 and after 3 and 6 months of therapy. In the benazepril group (n = 11), the diastolic transmitral flow of the E and A waves ratio (E/A ratio) increased significantly between 0 and 6 months (P = 0.009) and the thickness of the left ventricular free wall in systole (LVFWs) decreased significantly between 0 and 3 months (P = 0.04). In the diltiazem CD group (n = 5), none of the parameters varied significantly throughout the study. There was no difference between the benazepril and the diltiazem CD group throughout the study. Therefore, the variations observed for the E/A ratio and the LVFWs may have been incidental. Further studies will be needed to establish the role of benazepril in subclinical hypertrophic cardiomyopathy in cat. PMID:16734369

  10. Comparison of the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis.

    Science.gov (United States)

    Yamane, Tsuyoshi; Fujii, Yoko; Orito, Kensuke; Osamura, Kaori; Kanai, Takao; Wakao, Yoshito

    2008-12-01

    To compare the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis. 24 Beagles. 18 dogs underwent pulmonary arterial banding (PAB) to induce right ventricular pressure overload, and 6 healthy dogs underwent sham operations (thoracotomy only [sham-operated group]). Dogs that underwent PAB were allocated to receive 1 of 3 treatments (6 dogs/group): candesartan (1 mg/kg, PO, q 24 h [PABC group]), enalapril (0.5 mg/kg, PO, q 24 h [PABE group]), or no treatment (PABNT group). Administration of treatments was commenced the day prior to surgery; control dogs received no cardiac medications. Sixty days after surgery, right ventricular wall thickness was assessed echocardiographically and plasma renin activity, angiotensin-converting enzyme activity, and angiotensin I and II concentrations were assessed; all dogs were euthanatized, and collagenous fiber area, cardiomyocyte diameter, and tissue angiotensin-converting enzyme and chymase-like activities in the right ventricle were evaluated. After 60 days of treatment, right ventricular wall thickness, cardiomyocyte diameter, and collagenous fiber area in the PABNT and PABE groups were significantly increased, compared with values in the PABC and sham-operated groups. Chymase-like activity was markedly greater in the PABE group than in other groups. Results indicated that treatment with candesartan but not enalapril effectively prevented myocardial remodeling in dogs with experimentally induced subacute right ventricular pressure overload.

  11. Formulation Optimization and Ex Vivo and In Vivo Evaluation of Celecoxib Microemulsion-Based Gel for Transdermal Delivery.

    Science.gov (United States)

    Cao, Mengyuan; Ren, Lili; Chen, Guoguang

    2017-08-01

    Celecoxib (CXB) is a poorly aqueous solubility sulfonamide non-steroidal anti-inflammatory drug (NSAID). Hence, the formulation of CXB was selected for solubilization and bioavailability. To find out suitable formulation for microemulsion, the solubility of CXB in triacetin (oil phase), Tween 80 (surfactant), and Transcutol-P (co-surfactant) was screened respectively and optimized by using orthogonal experimental design. The Km value and concentration of oil, S mix , and water were confirmed by pseudo-ternary phase diagram studies and central composite design. One percent carbopol 934 was added to form CXB microemulsion-based gel. The final formulation was evaluated for its appearance, pH, viscosity, stability, drug content determination, globule size, and zeta potential. Its ex vivo drug permeation and the in vivo pharmacokinetic was investigated. Further research was performed to ensure the safety and validity by skin irritation study and in vivo anti-inflammatory activity study. Ex vivo permeation study in mice was designed to compare permeation and transdermal ability between microemulsion formulation and conventional gel. The results revealed that optimized microemulsion-based gel gained higher permeation based on smaller globule size and high drug loading of microemulsion. Transdermal ability was also greatly improved. Bioavailability was compared to market Celebrex® by the in vivo pharmacokinetic study in rabbits. The results indicated that CXB microemulsion-based gel had better bioavailability than Celebrex®.

  12. Physiological effects of indomethacin and celecobix: an S-transform laser Doppler flowmetry signal analysis

    International Nuclear Information System (INIS)

    Assous, S; Humeau, A; Tartas, M; Abraham, P; L'Huillier, J P

    2005-01-01

    Conventional signal processing typically involves frequency selective techniques which are highly inadequate for nonstationary signals. In this paper, we present an approach to perform time-frequency selective processing of laser Doppler flowmetry (LDF) signals using the S-transform. The approach is motivated by the excellent localization, in both time and frequency, afforded by the wavelet basis functions. Suitably chosen Gaussian wavelet functions are used to characterize the subspace of signals that have a given localized time-frequency support, thus enabling a time-frequency partitioning of signals. In this paper, the goal is to study the influence of various pharmacological substances taken by the oral way (celecobix (Celebrex (registered) ), indomethacin (Indocid (registered) ) and placebo) on the physiological activity behaviour. The results show that no statistical differences are observed in the energy computed from the time-frequency representation of LDF signals, for the myogenic, neurogenic and endothelial related metabolic activities between Celebrex and placebo, and Indocid and placebo. The work therefore proves that these drugs do not affect these physiological activities. For future physiological studies, there will therefore be no need to exclude patients having taken cyclo-oxygenase 1 inhibitions

  13. Physiological effects of indomethacin and celecobix: an S-transform laser Doppler flowmetry signal analysis

    Science.gov (United States)

    Assous, S.; Humeau, A.; Tartas, M.; Abraham, P.; L'Huillier, J. P.

    2005-05-01

    Conventional signal processing typically involves frequency selective techniques which are highly inadequate for nonstationary signals. In this paper, we present an approach to perform time-frequency selective processing of laser Doppler flowmetry (LDF) signals using the S-transform. The approach is motivated by the excellent localization, in both time and frequency, afforded by the wavelet basis functions. Suitably chosen Gaussian wavelet functions are used to characterize the subspace of signals that have a given localized time-frequency support, thus enabling a time-frequency partitioning of signals. In this paper, the goal is to study the influence of various pharmacological substances taken by the oral way (celecobix (Celebrex®), indomethacin (Indocid®) and placebo) on the physiological activity behaviour. The results show that no statistical differences are observed in the energy computed from the time-frequency representation of LDF signals, for the myogenic, neurogenic and endothelial related metabolic activities between Celebrex and placebo, and Indocid and placebo. The work therefore proves that these drugs do not affect these physiological activities. For future physiological studies, there will therefore be no need to exclude patients having taken cyclo-oxygenase 1 inhibitions.

  14. Comparison of tepoxalin, carprofen, and meloxicam for reducing intraocular inflammation in dogs.

    Science.gov (United States)

    Gilmour, Margi A; Lehenbauer, Terry W

    2009-07-01

    To compare effects of orally administered tepoxalin, carprofen, and meloxicam for controlling aqueocentesis-induced anterior uveitis in dogs, as determined by measurement of aqueous prostaglandin E(2) (PGE(2)) concentrations. 38 mixed-breed dogs. Dogs were allotted to a control group and 3 treatment groups. Dogs in the control group received no medication. Dogs in each of the treatment groups received an NSAID (tepoxalin, 10 mg/kg, PO, q 24 h; carprofen, 2.2 mg/kg, PO, q 12 h; or meloxicam, 0.2 mg/kg, PO, q 24 h) on days 0 and 1. On day 1, dogs were anesthetized and an initial aqueocentesis was performed on both eyes; 1 hour later, a second aqueocentesis was performed. Aqueous samples were frozen at -80 degrees C until assayed for PGE(2) concentrations via an enzyme immunoassay kit. Significant differences between aqueous PGE(2) concentrations in the first and second samples from the control group indicated that aqueocentesis induced uveitis. Median change in PGE(2) concentrations for the tepoxalin group (10 dogs [16 eyes]) was significantly lower than the median change for the control group (8 dogs [16 eyes]), carprofen group (9 dogs [16 eyes]), or meloxicam group (9 dogs [16 eyes]). Median changes in PGE(2) concentrations for dogs treated with meloxicam or carprofen were lower but not significantly different from changes for control dogs. Tepoxalin was more effective than carprofen or meloxicam for controlling the production of PGE(2) in dogs with experimentally induced uveitis. Tepoxalin may be an appropriate choice when treating dogs with anterior uveitis.

  15. Driving external chemistry optimization via operations management principles.

    Science.gov (United States)

    Bi, F Christopher; Frost, Heather N; Ling, Xiaolan; Perry, David A; Sakata, Sylvie K; Bailey, Simon; Fobian, Yvette M; Sloan, Leslie; Wood, Anthony

    2014-03-01

    Confronted with the need to significantly raise the productivity of remotely located chemistry CROs Pfizer embraced a commitment to continuous improvement which leveraged the tools from both Lean Six Sigma and queue management theory to deliver positive measurable outcomes. During 2012 cycle times were reduced by 48% by optimization of the work in progress and conducting a detailed workflow analysis to identify and address pinch points. Compound flow was increased by 29% by optimizing the request process and de-risking the chemistry. Underpinning both achievements was the development of close working relationships and productive communications between Pfizer and CRO chemists. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Progression of fibromyalgia: results from a 2-year observational fibromyalgia and chronic pain study in the US

    OpenAIRE

    Adams, Edgar H; McElroy, Heather J; Udall, Margarita; Masters, Elizabeth T; Mann, Rachael M; Schaefer, Caroline P; Cappelleri, Joseph C; Clair, Andrew G; Hopps, Markay; Daniel, Shoshana R; Mease, Philip; Silverman, Stuart L; Staud, Roland

    2016-01-01

    Edgar H Adams,1 Heather J McElroy,2 Margarita Udall,3 Elizabeth T Masters,3 Rachael M Mann,4 Caroline P Schaefer,1 Joseph C Cappelleri,5 Andrew G Clair,3 Markay Hopps,3 Shoshana R Daniel,6 Philip Mease,7,8 Stuart L Silverman,9,10 Roland Staud11 1Covance Market Access Services Inc, Gaithersburg, MD, USA; 2Covance (Asia) Pte Ltd, Singapore, Singapore; 3Pfizer Inc, New York, NY, 4Covance Market Access Services Inc, San Diego, CA, 5Pfizer Inc, Groton, CT, 6Covance Market Access Services Inc, Cons...

  17. canvasDesigner: A versatile interactive high-resolution scientific multi-panel visualization toolkit.

    Science.gov (United States)

    Zhang, Baohong; Zhao, Shanrong; Neuhaus, Isaac

    2018-05-03

    We present a bioinformatics and systems biology visualization toolkit harmonizing real time interactive exploring and analyzing of big data, full-fledged customizing of look-n-feel, and producing multi-panel publication-ready figures in PDF format simultaneously. Source code and detailed user guides are available at http://canvasxpress.org, https://baohongz.github.io/canvasDesigner, and https://baohongz.github.io/canvasDesigner/demo_video.html. isaac.neuhaus@bms.com, baohong.zhang@pfizer.com, shanrong.zhao@pfizer.com. Supplementary materials are available at https://goo.gl/1uQygs.

  18. Radioimmunoassay of type D oncovirus from continuous J-96 cells

    International Nuclear Information System (INIS)

    Vlasenkova, N.K.; Altshtejn, A.D.; Zhdanov, V.M.; Kitsak, V.Ya.

    1978-01-01

    The radioimmunoassay of the J-96 virus and an extract of J-96 cells in the homologous and heterologous systems aimed at detecting antigenic determinants of p25 of Mason-Pfizer virus and group-specific and interspecies antigenic determinants p30 of Rauscher leukaemia virus demonstrated that (1) J-96 virus contains a major internal protein immunologically identical with p25 protein of Mason-Pfizer virus based on the antigenic determinants detectable by the radioimmunoassay used; and (2) no interspecies antigenic determinants characteristic of the major internal protein of mammalian type C viruses were detectable in the J-96 virus or the J-96 cell extract. (author)

  19. Medical Vanguard Diabetes Management Project

    Science.gov (United States)

    2005-10-01

    Encefalitis Equina. Rev Panam Salud Publica , Jan. 1997, vol.1, no.1, p.78-83. ISSN 1020-4989. 8. CDC. Venezuelan Equine Encephalitis - Colombia, 1995. In...exhibition canceled due to equine encephalitis]. Panorama. 19 July 1995. 1—1. 42. PFIZER ADVERTISEMENT: La División de Salud Animal de Pfizer felicita...Carabobeño. 14 September 1995. C-5. 78. Por brote de encefalitis en el Zulia: Comisión de salud del congreso interpelará a ministros de sanidad y

  20. Multiple comparisons in drug efficacy studies: scientific or marketing principles?

    Science.gov (United States)

    Leo, Jonathan

    2004-01-01

    When researchers design an experiment to compare a given medication to another medication, a behavioral therapy, or a placebo, the experiment often involves numerous comparisons. For instance, there may be several different evaluation methods, raters, and time points. Although scientifically justified, such comparisons can be abused in the interests of drug marketing. This article provides two recent examples of such questionable practices. The first involves the case of the arthritis drug celecoxib (Celebrex), where the study lasted 12 months but the authors only presented 6 months of data. The second case involves the NIMH Multimodal Treatment Study (MTA) study evaluating the efficacy of stimulant medication for attention-deficit hyperactivity disorder where ratings made by several groups are reported in contradictory fashion. The MTA authors have not clarified the confusion, at least in print, suggesting that the actual findings of the study may have played little role in the authors' reported conclusions.

  1. Effect of honey consumption on intestinal motility in male albino rats ...

    African Journals Online (AJOL)

    Summary: This study investigated the effects of honey on intestinal motility and transit using twenty (20) male albino rats of Wistar strain weighing 210-220g. The rats were randomly grouped into control and honey-fed (test) groups of ten (10) rats each. The control group was fed on normal rat chow ( Pfizer Company, Nigeria ) ...

  2. original article candida species amongst pregnant women in benin

    African Journals Online (AJOL)

    Dr Oboro VO

    was used to streak Sabouraud Dextrose. Agar SDA (Oxoid, England) plates containing 0.5ml Chloramphenicol. (500mg,Pfizer) and incubated at 370C in triplicates. Uninoculated plain agar plates served as control for the inoculated ones. Discrete yeast colonies were subcultured on fresh SDA slants in. McCarthney bottles ...

  3. Mithramycin In Paget's Disease

    African Journals Online (AJOL)

    1974-06-29

    Jun 29, 1974 ... Mithramycin (kindly supplied by courtesy of. Pfizer Pharmaceuticals), was administered intravenously in a dose of 15 pg/kg body mass over 4 hours in 1 litre of '5% dextrose water solution. This dose was given daily as a course for 5 days. Further courses were given only if the patient failed to improve on the ...

  4. New Dimensions for Manufacturing: A UK Strategy for Nanotechnology

    Science.gov (United States)

    2002-06-01

    Semiconductors, Peratech, BP (Sunbury), Pfizer, Kodak, Unilever , Carpenter Technology, and Morgan-Matroc. Opinion is divided over whether companies based in the...14 Part 1: Background ...economy, even including companies in areas such as pharmaceuticals and chemicals where the UK still has a strong position. The likely extent of the

  5. Download this PDF file

    African Journals Online (AJOL)

    DR ADESOPE

    Calorimeter determination of phosphorus in soil and plant materials ... Vit: A Pfizer livestock feeds production supplying the following vitamins and minerals per gram of diet: A, 9823 I.U; D3, 1965 I.U.; B12, 10 g/ton; Riboflavin, 10mg; ...

  6. Evaluating smartphone-based stop smoking interventions – opportunities and challenges.

    Directory of Open Access Journals (Sweden)

    Aleksandra Herbec

    2017-05-01

    AH is funded by British Heart Foundation PhD Studentship at University College London. The costs of conducting BupaQuit trial have been funded by Bupa. NRT2Quit trial was funded through Global Research Awards for Nicotine Dependence (GRAND Program by Pfizer.

  7. Analyzing Differences Between Public and Private Sector Information Resource Management: Chief Information Officer Challenges and Critical Technologies

    Science.gov (United States)

    2002-01-01

    SCIENTIFIC CORPORATION 48 CONOCO INC 548 TRIAD HOSPITALS INC 49 PFIZER INC 549 POLYONE CORPORATION 50 J C PENNY 550 STARBUCKS CORPORATION 51...637 LA Z BOY 138 VALERO ENERGY CORPORATION 638 RYERSON TULL 139 MCDONALD S CORPORATION 639 CHIQUITA BRANDS INTERNATIONAL 140 WEYERHAEUSER COMPANY

  8. Microbiological quality of commercially available poultry feeds sold ...

    African Journals Online (AJOL)

    Food poisoning and infection by bacterial and fungal genera pose obvious health threat to both animals and humans. Pfizer, Guinea, Extra, Top, NOM and Master brands of feed sold in Owerri Metropolis were analysed for their bacterial and fungal quality. The genera of bacteria and fungi isolated and their percentage ...

  9. Translational medicine and drug discovery

    National Research Council Canada - National Science Library

    Littman, Bruce H; Krishna, Rajesh

    2011-01-01

    ..., and examples of their application to real-life drug discovery and development. The latest thinking is presented by researchers from many of the world's leading pharmaceutical companies, including Pfizer, Merck, Eli Lilly, Abbott, and Novartis, as well as from academic institutions and public- private partnerships that support translational research...

  10. 1620-IJBCS-Article-Dada Adekunle

    African Journals Online (AJOL)

    hp

    pelleting machine. The produced pellets were .... in fat contents as the feeding ration increased. Data on carcass ... Vegetable oil ... Vitamin premix – A Pfizer livestock product containing the following per kg of feed: A = 4500 I. U, D = 11252 I.U,.

  11. The metabolic consequences of thyroxine replacement in adult hypopituitary patients

    DEFF Research Database (Denmark)

    Filipsson Nyström, Helena; Feldt-Rasmussen, Ulla; Kourides, Ione

    2012-01-01

    The metabolic consequences of thyroxine replacement in patients with central hypothyroidism (CH) need to be evaluated. The aim was to examine the outcome of thyroxine replacement in CH. Adult hypopituitary patients (n = 1595) with and without CH from KIMS (Pfizer International Metabolic Database...

  12. Correction: Kikuchi, K., et al., Potential of the Angiotensin Receptor Blockers (ARBs Telmisartan, Irbesartan, and Candesartan for Inhibiting the HMGB1/RAGE Axis in Prevention and Acute Treatment of Stroke. Int. J. Mol. Sci. 2013, 14, 18899–18924.

    Directory of Open Access Journals (Sweden)

    Kiyoshi Kikuchi

    2014-03-01

    Full Text Available The original version of the paper [1] reports that “This ACTIVE I study was supported by Pfizer” (Page 18905. However, the sponsors of the ACTIVE I study were actually Bristol-Myers Squibb and Sanofi-Aventis rather than Pfizer.

  13. The barriers

    Indian Academy of Sciences (India)

    ... than for other diseases, which results in chronic underinvestment; reduced investment in TB drug R&D,. Pfizer withdrawal from TB R&D; AstraZeneca abandon TB R&D & close site; Novartis pull out; 4/22 Big Pharma producing antibacterials. Limited financial support to progress preclinical drug candidates from public sector.

  14. 75 FR 60308 - New Animal Drugs for Use in Animal Feeds; Melengestrol

    Science.gov (United States)

    2010-09-30

    .... FDA-2010-N-0002] New Animal Drugs for Use in Animal Feeds; Melengestrol AGENCY: Food and Drug... amending the animal drug regulations to more accurately reflect the recent approval of two supplemental new animal drug applications (NADAs) filed by Pharmacia & Upjohn Co., a Division of Pfizer, Inc. The...

  15. Optimized method for isolation of immature intracytoplasmic retroviral particles from mammalian cells

    Czech Academy of Sciences Publication Activity Database

    Langerová, Hana; Ruml, T.; Rumlová, M.

    2017-01-01

    Roč. 248, Oct (2017), s. 19-25 ISSN 0166-0934 Institutional support: RVO:61388963 Keywords : intracytoplasmic particles (ICAPs) * retrovirus * assembly * Mason-Pfizer monkey virus Subject RIV: EE - Microbiology, Virology OBOR OECD: Virology Impact factor: 1.693, year: 2016

  16. The accuracies of DNA-based estimates of genetic merit derived from Angus or multibreed beef cattle training populations.

    Science.gov (United States)

    Weber, K L; Drake, D J; Taylor, J F; Garrick, D J; Kuehn, L A; Thallman, R M; Schnabel, R D; Snelling, W M; Pollak, E J; Van Eenennaam, A L

    2012-12-01

    Several organizations have developed prediction models for molecular breeding values (MBV) for quantitative growth and carcass traits in beef cattle using Bovine SNP50 genotypes and phenotypic or EBV data. Molecular breeding values for Angus cattle have been developed by IGENITY, Pfizer Animal Genetics, and a collaboration between researchers from Iowa State University and the University of Missouri-Columbia (ISU/UMC). The U.S. Meat Animal Research Center (USMARC; Clay Center, NE) has also developed MBV for 16 cattle breeds using 2 multibreed populations, the Germplasm Evaluation (GPE) Program and the 2,000 Bull Project (2K(ALL)), and 2 single breed subpopulations of the 2,000 Bull Project, Angus (2K(AN)) and Hereford (2K(HH)). In this study, these MBV were assessed relative to commercial ranch EBV estimated from the progeny phenotypes of Angus bulls naturally mated in multisire breeding pastures to commercial cows: 121 for USMARC MBV, 99 for ISU/UMC MBV, and 29 for IGENITY and Pfizer MBV (selected based on number of progeny carcass records). Five traits were analyzed: weaning weight (WW), HCW, marbling score (MS), rib-eye muscle area (RE), and, for IGENITY and Pfizer only, feedlot ADG. The average accuracies of MBV across traits were 0.38 ± 0.05 for IGENITY, 0.61 ± 0.12 for Pfizer, 0.46 ± 0.12 for ISU/UMC, 0.16 ± 0.04 for GPE, 0.26 ± 0.05 for 2K(ALL), 0.24 ± 0.04 for 2K(AN), and 0.02 ± 0.12 for 2K(HH). Angus-based MBV (IGENITY, Pfizer, ISU/UMC, and 2K(AN)) explained larger proportions of genetic variance in this population than GPE, 2K(ALL), or 2K(HH) MBV for the same traits. In this data set, IGENITY, Pfizer, and ISU/UMC MBV were predictive of realized performance of progeny, and incorporation of that information into national genetic evaluations would be expected to improve EPD accuracy, particularly for young animals.

  17. Business Process Flow Diagrams in Tissue Bank Informatics System Design, and Identification and Communication of Best Practices: The Pharmaceutical Industry Experience.

    Science.gov (United States)

    McDonald, Sandra A; Velasco, Elizabeth; Ilasi, Nicholas T

    2010-12-01

    Pfizer, Inc.'s Tissue Bank, in conjunction with Pfizer's BioBank (biofluid repository), endeavored to create an overarching internal software package to cover all general functions of both research facilities, including sample receipt, reconciliation, processing, storage, and ordering. Business process flow diagrams were developed by the Tissue Bank and Informatics teams as a way of characterizing best practices both within the Bank and in its interactions with key internal and external stakeholders. Besides serving as a first step for the software development, such formalized process maps greatly assisted the identification and communication of best practices and the optimization of current procedures. The diagrams shared here could assist other biospecimen research repositories (both pharmaceutical and other settings) for comparative purposes or as a guide to successful informatics design. Therefore, it is recommended that biorepositories consider establishing formalized business process flow diagrams for their laboratories, to address these objectives of communication and strategy.

  18. Viagra selfhood: pharmaceutical advertising and the visual formation of Swedish masculinity.

    Science.gov (United States)

    Asberg, Cecilia; Johnson, Ericka

    2009-06-01

    Using material from the Pfizer sponsored website providing health information on erectile dysfunction to potential Swedish Viagra customers (www.potenslinjen.se), this article explores the public image of masculinity in relation to sexual health and the cultural techniques for creating pharmaceutical appeal. We zoom in on the targeted ideal users of Viagra, and the nationalized, racialized and sexualized identities they are assigned. As part of Pfizer's marketing strategy of adjustments to fit the local consumer base, the ways in which Viagra is promoted for the Swedish setting is telling of what concepts of masculinity are so stable and unassailable that they can withstand the association with a drug that is, in essence, an acknowledgement of 'failed' masculinity and 'dysfunctional' sexuality. With comparative national examples, this study presents an interdisciplinary take on the 'glocalized' cultural imaginary of Viagra, and the masculine subject positions it engenders.

  19. Coprescribing proton-pump inhibitors with nonsteroidal anti-inflammatory drugs: risks versus benefits

    Directory of Open Access Journals (Sweden)

    Gwee KA

    2018-02-01

    Full Text Available Kok Ann Gwee,1 Vernadine Goh,2 Graca Lima,3 Sajita Setia4 1Stomach, Liver, and Bowel Centre, Gleneagles Hospital, 2Department of Pharmacy, National University of Singapore, Singapore; 3Global Medical Affairs, Asia-Pacific Region, Pfizer, Hong Kong; 4Medical Affairs, Pfizer, Singapore Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs are often coadministered with proton-pump inhibitors (PPIs to reduce NSAID-induced gastrointestinal (GI adverse events. This coadministration is generally regarded as safe, and is included in many of the guidelines on NSAID prescription. However, recent evidence indicates that the GI risks associated with NSAIDs can be potentiated when they are combined with PPIs. This review discusses the GI effects and complications of NSAIDs and how PPIs may potentiate these effects, options for prevention of GI side effects, and appropriate use of PPIs in combination with NSAIDs. Keywords: PPIs, COX2 inhibitors, NSAIDs, enteropathy, gastrointestinal

  20. Partnerships in Pharma--An Economist Intelligence Unit Seminar--Building Innovation into Alliances and Business Models. 1 October 2010, London, UK.

    Science.gov (United States)

    Kibble, Alexandra

    2010-12-01

    The Partnerships in Pharma seminar, held in London, included topics related to building innovation into alliances and business models within the pharmaceutical industry. This conference report highlights selected presentations on strategies for successful partnering, partnering alongside an evolving CRO industry, considering the pharma value chain, and partnerships between industry and academia. Approaches used by Ipsen, Merck Serono, Pfizer and ViiV Healthcare are also described.

  1. Maraviroc (UK-427,857), a Potent, Orally Bioavailable, and Selective Small-Molecule Inhibitor of Chemokine Receptor CCR5 with Broad-Spectrum Anti-Human Immunodeficiency Virus Type 1 Activity

    OpenAIRE

    Dorr, Patrick; Westby, Mike; Dobbs, Susan; Griffin, Paul; Irvine, Becky; Macartney, Malcolm; Mori, Julie; Rickett, Graham; Smith-Burchnell, Caroline; Napier, Carolyn; Webster, Rob; Armour, Duncan; Price, David; Stammen, Blanda; Wood, Anthony

    2005-01-01

    Maraviroc (UK-427,857) is a selective CCR5 antagonist with potent anti-human immunodeficiency virus type 1 (HIV-1) activity and favorable pharmacological properties. Maraviroc is the product of a medicinal chemistry effort initiated following identification of an imidazopyridine CCR5 ligand from a high-throughput screen of the Pfizer compound file. Maraviroc demonstrated potent antiviral activity against all CCR5-tropic HIV-1 viruses tested, including 43 primary isolates from various clades a...

  2. Assessing the adaptation and implementation fidelity of an Online Tobacco Cessation Training Program for Healthcare Professionals in three Spanish-speaking Latin American countries: The Fruitful Study

    Directory of Open Access Journals (Sweden)

    Cristina Martínez

    2017-05-01

    This study has been funded by Global Bridges Mayo Clinic (Pfizer Medical Group; GB-13520139: Development and Dissemination of a Tobacco Cessation Training Program for Healthcare Professionals in Spanish-speaking Countries. Moreover, CM and EF are also funded by the Spanish Government (Instituto de Salut Carlos III, grant PI15-00875 and the Catalan Government (Xarxa Catalana d’Hospitals sense fum, Agència de Salut Pública de Catalunya, contracte Nº 2015VAR171

  3. Skin permeability and pharmacokinetics of diclofenac epolamine administered by dermal patch in Yorkshire-Landrace pigs

    OpenAIRE

    Tse S; Powell KD; MacLennan SJ; Moorman AR; Paterson C; Bell RR

    2012-01-01

    Susanna Tse,1 Kendall D Powell,2 Stephen MacLennan,3 Allan R Moorman,4 Craig Paterson,5 Rosonald R Bell11Pfizer Inc, Groton, CT, USA; 2Tandem Labs, Durham, NC, USA; 3BioCryst Pharmaceuticals Inc, Durham, NC, USA; 4Alta Vetta Pharmaceutical Consulting LLC, Durham, NC, USA; 5Salix Pharmaceuticals Inc, Raleigh, NC, USAPurpose: This study compared the pharmacokinetic profile, and systemic and local absorption of diclofenac, following dermal patch application and oral administration in Yorkshire- ...

  4. Computed tomography of the sacrum: 1. normal anatomy

    International Nuclear Information System (INIS)

    Whelan, M.A.; Gold, R.P.

    1982-01-01

    The sacrum of a disarticulated pelvis was scanned with a Pfizer 0450 computed tomographic scanner using contiguous 5 mm sections to display the normal computed tomographic anatomy of the sacrum. These anatomic sections were then compared with normal sacrums. In analyzing the computed tomographic anatomy, emphasis was placed on the central canal and sacral foramina, in that these landmarks are important in determining not only the presence but also the type of pathology involving the sacrum

  5. Economic and humanistic burden of post-trauma and post-surgical neuropathic pain among adults in the United States

    OpenAIRE

    Sadosky, Alesia; Parsons,Bruce; Schaefer,Caroline; Mann,Rachael; Daniel,Shoshana; Nalamachu,Srinivas; Stacey,Brett R; Nieshoff,Edward C; Tuchman,Michael; Anschel,Alan

    2013-01-01

    Bruce Parsons,1 Caroline Schaefer,2 Rachael Mann,3 Alesia Sadosky,1 Shoshana Daniel,4 Srinivas Nalamachu,5 Brett R Stacey,6 Edward C Nieshoff,7 Michael Tuchman,8 Alan Anschel91Pfizer, Inc, New York, NY, USA; 2Covance Market Access Services, Inc, Gaithersburg, MD, USA; 3Covance Market Access Services, Inc, San Diego, CA, USA; 4Covance Market Access Services, Inc, Conshohocken, PA, USA; 5International Clinical Research Institute, Overland Park, KS, USA; 6Oregon Health and Science University, Po...

  6. [23 and Me: how to make (a lot of) money out of your customers].

    Science.gov (United States)

    Jordan, Bertrand

    2015-04-01

    The announcement of several deals between the DTC genetics firm 23 and Me and Genentech, Pfizer and other corporations reveals the real business model of the company: selling access to sets of characterized patients for targeted drug development. This may be a useful strategy, but it raises a number of questions concerning the privacy of the company's customers and also of adequate compensation when they become valuable currency. © 2015 médecine/sciences – Inserm.

  7. American Academy of Allergy, Asthma and Immunology (AAAAI)-2010 annual meeting. 26 February-2 March 2010, New Orleans, LA, USA.

    Science.gov (United States)

    Bielory, Leonard

    2010-05-01

    The 2010 American Academy of Allergy, Asthma and Immunology (AAAAI) meeting, held in New Orleans, included topics covering new therapeutic developments in the fields of allergy, asthma and immunological diseases. This conference report highlights selected presentations on potential treatments for food and other allergies, as well as therapies for asthma and other immunological diseases. Investigational drugs discussed include Oralair Mites (Stallergenes SA/Paladin Labs Inc), PF-03654746 (Pfizer Inc) and AMG-853 (Amgen Inc).

  8. Structure of the immature retroviral capsid at 8 angstrom resolution by cryo-electron microscopy

    Czech Academy of Sciences Publication Activity Database

    Bharat, T. A. M.; Davey, N. E.; Ulbrich, P.; Riches, J. D.; de Marco, A.; Rumlová, Michaela; Sachse, C.; Ruml, T.; Briggs, J. A. G.

    2012-01-01

    Roč. 487, č. 7407 (2012), s. 385-389 ISSN 0028-0836 R&D Projects: GA ČR GA204/09/1388 Grant - others:GA ČR(CZ) GAP302/12/1895 Institutional research plan: CEZ:AV0Z40550506 Keywords : Pfizer monkey virus * terminal domain * HIV -1 virions * nucleic-acid Subject RIV: CE - Biochemistry Impact factor: 38.597, year: 2012

  9. Molecular Mechanisms and Treatment Strategies for Obesity-Associated Coronary Artery Disease, an Imminent Military Epidemic

    Science.gov (United States)

    2007-12-01

    in response to another ‘hit.’ This two-hit model of UPR-induced apoptosis is critical to understanding how FC enrichment kills macrophages. In this...Schering- Plough Research Grant, 1989-1995, Responsible Investigator, $50,000 per annum Individual National Research Supplement Award for Postdoctoral...Association grant-in-aid study section (1994) Consultant for Merck, Schering- Plough , Warner-Lambert, Berlex, Eli Lilly, Pfizer, Talaria Biotech, ReddyUS

  10. The role of S-S bridge in retroviral protease function and virion maturation

    Czech Academy of Sciences Publication Activity Database

    Zábranská, Helena; Tůma, R.; Kluh, Ivan; Svatoš, A.; Ruml, Tomáš; Hrabal, R.; Pichová, Iva

    2007-01-01

    Roč. 365, č. 5 (2007), s. 1493-1504 ISSN 0022-2836 R&D Projects: GA MŠk 1M0508; GA MŠk 1M0520; GA ČR GESCO/06/E001 Institutional research plan: CEZ:AV0Z40550506 Keywords : retroviral protease * Mason-Pfizer monkey virus * disulfide * dimerization Subject RIV: CE - Biochemistry Impact factor: 4.472, year: 2007

  11. Charakterizace integrasy Masonova-Pfizerova opičího viru

    Czech Academy of Sciences Publication Activity Database

    Krejčík, Z.; Snášel, Jan; Rosenberg, Ivan; Ruml, T.; Pichová, Iva

    2002-01-01

    Roč. 96, č. 4 (2002), s. 223 ISSN 0009-2770. [Sigma-Aldrich konference mladých chemiků, biochemiků a molekulárních biologů. 22.05.2002-25.05.2002, Velké Meziříčí] Institutional research plan: CEZ:AV0Z4055905 Keywords : Mason-Pfizer monkey virus Subject RIV: CE - Biochemistry

  12. Role bazické oblasti nukleokapsidového proteinu Masonova-Pfizerova opičího viru během skládání nezralých retrovirových částic

    Czech Academy of Sciences Publication Activity Database

    Dostálková, A.; Hadravová, Romana; Rumlová, M.

    2016-01-01

    Roč. 14, č. 2 (2016), s. 58-59 ISSN 2336-7202. [Mezioborové setkání mladých biologů, biochemiků a chemiků /16./. 10.05.2016-13.05.2016, Milovy] R&D Projects: GA ČR(CZ) GA14-15326S Institutional support: RVO:61388963 Keywords : M-PMV * Mason-Pfizer monkey virus * nucleocapsid protein Subject RIV: EE - Microbiology, Virology

  13. CINRG: Infrastructure for Clinical Trials in Duchenne Dystrophy

    Science.gov (United States)

    2012-09-01

    Cardiac Outcome Measures in Children with Muscular Dystrophy o Cardiac MRI Protocol: PITT0110 - Cardiac Magnetic Resonance: A Parallel Protocol...permitted during the study. Study drug. The study drug was PTX (Trental; Sanofi- Aventis U.S. LLC, Bridgewater, NJ) tablets , an FDA-approved pharmaceutical...that is available for oral administration as 400-mg oblong tablets . Both the study drug PTX and placebo were overencapsulated by Capsugel (Pfizer Inc

  14. Acquiring Pharmaceutical Industry Assets in the UK: 1 + 1 = 1?

    Science.gov (United States)

    Kanavos, Panos; Angelis, Aris

    2014-01-01

    The recent AstraZeneca takeover bid from Pfizer puts pharmaceutical R&D once again on the public agenda. Three pertinent questions are (a) what can be expected from this acquisition, (b) what are the implications for the UK economy and science base, and (c) whether such a deal should go ahead. Although the key driver behind this acquisition would be an improvement in company performance and shareholder value, past evidence suggests that mergers and acquisitions (M&A) of large pharmaceutical companies imply a neutral net effect on productivity, if not a decline, with employment decreasing and R&D spend following a similar trend. Similarities between the two companies include dropping sales; however, relative to its size, AstraZeneca has a more promising R&D pipeline, especially in therapeutic areas where Pfizer's strength is currently limited (e.g. oncology). Ensuring a portfolio diversification would make Pfizer's takeover proposal a knight's one, but history points towards a knave-like behavior.

  15. The relationship between 24 h/4 h radioiodine-131 uptake ratio and outcome after radioiodine therapy in 1402 patients with solitary autonomously functioning thyroid nodules

    International Nuclear Information System (INIS)

    Filesi, M.; Travascio, L.; Montesano, T.

    2009-01-01

    The objective of this study was to evaluate the role of 24 h/4 h uptake ratio (UR) in response to radioiodine-131 ( 131 I) therapy in patients with autonomously functioning thyroid nodules (AFTN). A total of 1402 consecutive hyperthyroid patients were treated with 131 I, between 1958 and 2005. Therapeutic doses (D) were calculated according to the formula: D=weight of nodule x dose per gram of nodular tissue (q)/24 h 131 I uptake. The ratios of the 24 and 4 h uptake were retrospectively calculated and the patients were grouped according to outcome and q into three groups of UR (≤1.25; 1.26-1.68; ≥1.69) by means of terziles. Of the 1402 patients, 95 did not respond to 131 I treatment while 93/1307 developed hypothyroidism. Most non-responders (55.8%) had UR ≤1.25, while many hypothyroid patients (66.7%) had UR ≥1.69 (χ 2 : P 131 I treatment, increasing to 13.9% at 5 years and 26.2% at 10 years. The 131 I UR can predict the outcome of 131 I treatment in AFTN and may have utility in modifying treatment in some patients to limit post-radioiodine induced hypothyroidism and treatment failures in order to achieve euthyroidism. (author)

  16. Transitional cell carcinoma involving the ductus deferens in a dog.

    Science.gov (United States)

    Guerin, Vincent J; 't Hooft, Krista W Visser; L'Eplattenier, Henry F; Petite, Audrey F

    2012-02-15

    A 12-year-old neutered male Springer Spaniel was referred with a 1-year history of recurring urinary tract infections. Repeated treatment with appropriate antimicrobials selected on the basis of bacterial culture and antimicrobial susceptibility results would result in clinical improvement, but recurrence of clinical signs was observed within days after discontinuation of treatment. Ultrasound examination revealed a tubular, fluid-filled structure dorsal to the bladder that extended from the midlevel of the bladder to the cranial pole of the prostate. Mineralized foci within a heterogeneous prostatic parenchyma were also noted. Dilation of the right ductus deferens (DD) was observed during exploratory laparotomy. Both DD were surgically removed, and the prostate was biopsied. The histopathological diagnosis was transitional cell carcinoma involving the right DD and the prostate. The dog was treated with meloxicam (0.1 mg/kg [0.05 mg/lb], p.o., q 24 h) for 9 months after diagnosis before being euthanized. Because the normal DD is rarely visualized during abdominal ultrasonography in dogs, identification of a tubular, fluid-filled structure dorsal to the bladder may indicate an abnormal DD. Transitional cell carcinoma of the DD should be included in the differential diagnoses of affected patients examined for clinical signs involving the urinary tract.

  17. Potassium iodide capsule treatment of feline sporotrichosis.

    Science.gov (United States)

    Reis, Erica G; Gremião, Isabella D F; Kitada, Amanda A B; Rocha, Raphael F D B; Castro, Verônica S P; Barros, Mônica B L; Menezes, Rodrigo C; Pereira, Sandro A; Schubach, Tânia M P

    2012-06-01

    Sporotrichosis is a mycosis caused by Sporothrix schenckii. The most affected animal is the cat; it has played an important role in the zoonotic transmission of this disease, especially in Rio de Janeiro, Brazil, since 1998. In order to evaluate the treatment of feline sporotrichosis with potassium iodide, an observational cohort was conducted in 48 cats with sporotrichosis at Instituto de Pesquisa Clínica Evandro Chagas, Fiocruz. All cats received potassium iodide capsules, 2.5 mg/kg to 20 mg/kg q24h. The cure rate was 47.9%, treatment failure was 37.5%, treatment abandonment was 10.4% and death was 4.2%. Clinical adverse effects were observed in 52.1% of the cases. Thirteen cats had a mild increase in hepatic transaminase levels during the treatment, six of them presented clinical signs suggestive of hepatotoxicity. Compared to previous studies with itraconazole and iodide in saturated solution, potassium iodide capsules are an alternative for feline sporotrichosis treatment.

  18. Pharmacokinetics of Short- and Long-acting Formulations of Oxytetracycline After Intramuscular Administration in Chickens.

    Science.gov (United States)

    Gberindyer, Aondover F; Okpeh, Ene R; Semaka, Asaaga A

    2015-12-01

    Both short- and long-acting formulations of oxytetracycline are commonly used in veterinary medicine to treat animals infected with gram-negative and gram-positive bacteria, rickettsiae, mycoplasma, and chlamydiae. To compare pharmacokinetics of short- and long-acting oxytetracycline in chickens, injectable formulations from the same pharmaceutical company were administered to healthy 6-week-old broiler chickens in accordance to the labeled instructions. Fourteen chickens were separated into 2 groups: chickens in group A (n = 7) were administered the short-acting formulation (10 mg/kg IM q24h) for 4 consecutive days, whereas those in group B (n = 7) were treated with a single dose (20 mg/kg IM) of the long-acting formulation. Blood samples were collected into heparinized tubes before and at 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, and 24 hours after initial treatment. Thereafter, blood samples were taken every 24 hours up to 120 hours. Plasma concentrations of oxytetracycline were determined by competitive enzyme-linked immunoabsorbent assay, and pharmacokinetic parameters were obtained. Both formulations delivered therapeutic plasma concentrations of oxytetracycline for approximately 100% of their respective dosing intervals as recommended. However, considering the additional labor, patient stress, and mortalities associated with handling, in addition to rejection of the carcass due to tissue necrosis resulting from multiple injections, we recommend use of the long-acting instead of the short-acting injectable formulation in broiler chickens.

  19. The efficacy and safety of a novel lipophilic formulation of methimazole for the once daily transdermal treatment of cats with hyperthyroidism.

    Science.gov (United States)

    Hill, K E; Gieseg, M A; Kingsbury, D; Lopez-Villalobos, N; Bridges, J; Chambers, P

    2011-01-01

    Previous studies on transdermal methimazole have used pluronic lecithin organogel as the vehicle. This might not be the most suitable vehicle for a lipophilic drug, such as methimazole. Once daily transdermal administration of a novel lipophilic formulation of methimazole is as safe and effective as oral carbimazole in treating hyperthyroidism in cats. Forty-five client-owned cats diagnosed with hyperthyroidism. Prospective study. Cats with newly diagnosed, untreated hyperthyroidism were treated with carbimazole (5 mg p.o., q12h) or methimazole (10 mg) applied to the inner pinnae q24h. Cats were examined after 0, 1, 4, 8, and 12 weeks of treatment. Clinical signs, body weight, systolic blood pressure, hematologic, serum biochemical and urine parameters, total serum thyroxine concentrations (TT4), and serum methimazole concentrations were recorded. No significant differences between groups were detected at day 0. Both formulations were effective in treating hyperthyroidism. No significant differences were detected in thyroxine concentrations, body weight, blood pressure, heart rate, alkaline phosphatase, alanine aminotransferase, creatinine, urea, and urine specific gravity (USG) between groups. The serum methimazole concentrations correlated poorly with TT4-concentrations in both groups. In this 12-week trial, once daily application of a novel formulation of transdermal methimazole applied to the pinnae was as effective and safe as twice daily oral carbimazole in the treatment of cats with hyperthyroidism. This novel formulation and transdermal application could have practical advantages to some pet owners. Copyright © 2011 by the American College of Veterinary Internal Medicine.

  20. Pharmacokinetic/Pharmacodynamic Modeling of Renin-Angiotensin Aldosterone Biomarkers Following Angiotensin-Converting Enzyme (ACE) Inhibition Therapy with Benazepril in Dogs.

    Science.gov (United States)

    Mochel, Jonathan P; Fink, Martin; Peyrou, Mathieu; Soubret, Antoine; Giraudel, Jérôme M; Danhof, Meindert

    2015-06-01

    The objective of this research was to provide a comprehensive description of the effect of benazepril on the dynamics of the renin-angiotensin aldosterone system (RAAS) in dogs. Blood specimens for renin activity (RA), angiotensin II (AII), and aldosterone (ALD) quantitation in plasma were drawn from 12 healthy adult beagle dogs randomly allocated to 2 treatment groups: (i) benazepril 5 mg PO, q24 h (n: 6) and (ii) placebo (n: 6), in a cross-over design. A mechanism-based pharmacokinetic/pharmacodynamic model, which includes the periodic nature of RA, AII, and ALD during placebo treatment and the subsequent changes in dynamics following repeated dosing with benazepril, was developed. The disposition kinetics of benazepril active metabolite, benazeprilat, was characterized using a saturable binding model to the angiotensin converting enzyme. The modulatory effect of benazeprilat on the RAAS was described using a combination of immediate response models. Our data show that benazepril noticeably influences the dynamics of the renin cascade, resulting in a substantial decrease in AII and ALD, while increasing RA throughout the observation span. The model provides a quantitative framework for better understanding the effect of ACE inhibition on the dynamics of the systemic RAAS in dogs.

  1. A randomized controlled clinical trial of the use of benazepril and heparin for the treatment of chronic kidney disease in dogs.

    Science.gov (United States)

    Tenhündfeld, Jörg; Wefstaedt, Patrick; Nolte, Ingo J A

    2009-04-15

    To investigate the effects of benazepril and heparin on renal function and blood pressure in dogs with chronic kidney disease. Randomized controlled clinical trial. 26 dogs with chronic kidney disease. Dogs were randomly assigned to receive benazepril hydrochloride (0.5 mg/kg [0.23 mg/lb], PO, q 24 h; n = 10), benazepril and heparin (150 U/kg [68 U/lb], SC, q 8 h, for the first 6 days; 10), or a placebo (6) and were followed up for 180 days. Health status score at the end of the study (ie, day 180) was significantly higher for dogs in the 2 treatment groups than for dogs in the placebo group. In addition, glomerular filtration rate was significantly increased and the urine protein-to-creatinine ratio was significantly decreased, compared with baseline rates, at the end of the study for dogs in both treatment groups but not for dogs in the placebo group. Systolic and diastolic blood pressures were significantly decreased on day 6 for dogs in both treatment groups. Results suggested that administration of benazepril had beneficial effects in dogs with chronic kidney disease but that short-term administration of heparin in conjunction with benazepril did not appear to provide any additional benefit.

  2. Successful treatment of vaginal malakoplakia in a young cat

    Directory of Open Access Journals (Sweden)

    Ryan P Cattin

    2016-10-01

    Full Text Available Case summary A 3-year-old, female, spayed, domestic shorthair cat presented for dysuria and haematuria, unresponsive to antibiotic treatment. A small, fleshy, erythematous mass protruded from the vaginal vault. Ultrasound identified a vaginal mass effect with mixed echogenicity measuring in excess of 3 cm. Vaginoscopy confirmed an extensive, fleshy, irregular mass that was characterised histologically as pyogranulomatous vaginitis, with periodic acid–Schiff-positive macrophages containing gram-negative bacteria. Fluorescence in situ hybridisation analysis demonstrated invasive intracellular Escherichia coli. Vaginal malakoplakia was diagnosed. Tissue culture and antimicrobial susceptibility of E coli was used to guide treatment. A 6 week course of enrofloxacin 5 mg/kg q24h resulted in complete resolution of the mass and clinical signs. Relevance and novel information Malakoplakia is a rare chronic inflammatory condition that has been previously reported in the bladder of two cats. The pathogenesis of malakoplakia is thought to involve ineffective killing of bacteria (eg. E coli , similar to granulomatous colitis in Boxers and French Bulldogs. The literature on malakoplakia in cats is sparse. This is the first reported feline case with vaginal involvement, intracellular E coli and successful treatment with a fluoroquinolone. Malakoplakia is an important, non-neoplastic differential diagnosis when a mass is identified in the urogenital system of a young cat.

  3. Life-threatening haematological complication occurring in a cat after chronic carbimazole administration

    Directory of Open Access Journals (Sweden)

    Andrea Mosca

    2016-09-01

    Full Text Available Case summary An 11-year-old spayed female domestic shorthair cat with a history of hyperthyroidism treated with carbimazole for 7 months was presented for a check-up after a few episodes of vomiting. The cat had been receiving prednisolone at 0.5 mg/kg PO q12h for recent pancreatitis and concurrent inflammation of liver and small intestines confirmed by biopsies. Clinical examination revealed pale mucous membranes with a capillary refill time of 120 s and fibrinogen serum concentration (3.5 g/l. Morphological changes of thrombocytes in the absence of thrombocytopenia were also noted. In-saline agglutination test was positive. Abdominal radiographic and ultrasonographic examinations excluded the presence of organ abnormalities and peritoneal effusion. Blood biochemistry was unremarkable. Feline leukaemia virus and feline immunodeficiency virus tests were negative. On the basis of these findings, immune-mediated anaemia secondary to chronic carbimazole administration was suspected. Prednisolone was increased to 2 mg/kg PO q24h and carbimazole tablets were stopped. Despite close monitoring and intensive care, the cat died the same evening of admission to the hospital. Relevance and novel information This report suggests that severe haemotoxicity may occur as a sequel of chronic carbimazole administration in cats. Routine bloodwork and accurate follow-up of cats under treatment with thyrotoxic therapy may be advisable, in order to detect haematological changes before lethal complications occur.

  4. Evaluation of fenbendazole for treatment of Giardia infection in cats concurrently infected with Cryptosporidium parvum.

    Science.gov (United States)

    Keith, Carey L; Radecki, Steven V; Lappin, Michael R

    2003-08-01

    To determine whether fenbendazole effectively eliminates Giardia organisms from chronically infected cats that have a concurrent Cryptosporidium parvum infection. 16 clinically normal cats. Eight cats with chronic concurrent Giardia and C parvum infections received fenbendazole (50 mg/kg, PO, q 24 h) for 5 days (treatment-group cats). Feces from each cat were collected and processed 3 days weekly for 23 days after treatment. By use of an immunofluorescent assay for detection of Giardia lamblia cysts and C parvum oocysts, organism numbers were counted and scored. Fecal results from treatment-group cats were compared with those of 8 untreated cats with Giardia infection but no C parvum infection (control-group cats). Four of 8 treatment-group cats had consistently negative results for Giardia infection after treatment. These 4 cats had consistently positive results for C parvum oocysts prior to treatment and consistently negative results after treatment. One treatment-group cat had positive results for cysts on all fecal samples, and 3 treatment-group cats had 1 to 3 negative results and then resumed shedding large numbers of cysts; each of these cats had consistently positive results for C parvum oocysts. When compared with control-group cats, treatment-group cats shed less Giardia cysts during week 1 after treatment but not during week 2. Administration of fenbendazole decreases Giardia cyst shedding to less than detectable numbers in some cats. In our study, persistent C parvum infection may have been associated with failure of fenbendazole to eliminate Giardia infection.

  5. Trichomonosis in cats with diarrhoea in Hong Kong, China, between 2009 and 2014

    Directory of Open Access Journals (Sweden)

    Liza S Köster

    2015-12-01

    Full Text Available Case series summary Infection of the domestic cat by Tritrichomonas blagburni, previously referred to as T foetus, may lead to a disease called feline trichomonosis, which manifests clinically as large bowel diarrhoea. The disease has a wide geographical distribution, including numerous countries in Europe, North America and Australia/Oceania. Nevertheless, it has occasionally been reported in Asia, South Korea and Japan. A retrospective study was carried out to include all domestic cats with diarrhoea, presented to two veterinary clinics in Hong Kong, China, between 1 July 2009 and 30 June 2014. A total of 29 cats with diarrhoea were diagnosed with Tritrichomonas species infection by means of quantitative PCR and direct microscopy. Tritrichomonas species was more frequently found in young (median age 10 months, male (66% and purebred cats (86%. Giardia species was found in 31% of Tritrichomonas species-positive cats. The recommended dose of ronidazole (30 mg/kg q24h for 14 days resolved clinical signs in 83% of diagnosed cats. Relevance and novel information This case series describes Tritrichomonas species as a cause for feline chronic diarrhoea in cats in China. The high rate of failure (17% in those cats receiving a standard regimen of ronidazole might be due to owner or patient compliance rather than protozoal resistance to the drug.

  6. Implementation of a publication strategy in the context of reporting biases. A case study based on new documents from Neurontin litigation.

    Science.gov (United States)

    Vedula, S Swaroop; Goldman, Palko S; Rona, Ilyas J; Greene, Thomas M; Dickersin, Kay

    2012-08-13

    Previous studies have documented strategies to promote off-label use of drugs using journal publications and other means. Few studies have presented internal company communications that discussed financial reasons for manipulating the scholarly record related to off-label indications. The objective of this study was to build on previous studies to illustrate implementation of a publication strategy by the drug manufacturer for four off-label uses of gabapentin (Neurontin, Pfizer, Inc.): migraine prophylaxis, treatment of bipolar disorders, neuropathic pain, and nociceptive pain. We included in this study internal company documents, email correspondence, memoranda, study protocols and reports that were made publicly available in 2008 as part of litigation brought by consumers and health insurers against Pfizer for fraudulent sales practices in its marketing of gabapentin (see http://pacer.mad.uscourts.gov/dc/cgi-bin/recentops.pl?filename=saris/pdf/ucl%20opinion.pdf for the Court's findings).We reviewed documents pertaining to 20 clinical trials, 12 of which were published. We categorized our observations related to reporting biases and linked them with topics covered in internal documents, that is, deciding what should and should not be published and how to spin the study findings (re-framing study results to explain away unfavorable findings or to emphasize favorable findings); and where and when findings should be published and by whom. We present extracts from internal company marketing assessments recommending that Pfizer and Parke-Davis (Pfizer acquired Parke-Davis in 2000) adopt a publication strategy to conduct trials and disseminate trial findings for unapproved uses rather than an indication strategy to obtain regulatory approval. We show internal company email correspondence and documents revealing how publication content was influenced and spin was applied; how the company selected where trial findings would be presented or published; how publication of

  7. Implementation of a publication strategy in the context of reporting biases. A case study based on new documents from Neurontin® litigation

    Directory of Open Access Journals (Sweden)

    Vedula S

    2012-08-01

    Full Text Available Abstract Background Previous studies have documented strategies to promote off-label use of drugs using journal publications and other means. Few studies have presented internal company communications that discussed financial reasons for manipulating the scholarly record related to off-label indications. The objective of this study was to build on previous studies to illustrate implementation of a publication strategy by the drug manufacturer for four off-label uses of gabapentin (Neurontin®, Pfizer, Inc.: migraine prophylaxis, treatment of bipolar disorders, neuropathic pain, and nociceptive pain. Methods We included in this study internal company documents, email correspondence, memoranda, study protocols and reports that were made publicly available in 2008 as part of litigation brought by consumers and health insurers against Pfizer for fraudulent sales practices in its marketing of gabapentin (see http://pacer.mad.uscourts.gov/dc/cgi-bin/recentops.pl?filename=saris/pdf/ucl%20opinion.pdf for the Court’s findings. We reviewed documents pertaining to 20 clinical trials, 12 of which were published. We categorized our observations related to reporting biases and linked them with topics covered in internal documents, that is, deciding what should and should not be published and how to spin the study findings (re-framing study results to explain away unfavorable findings or to emphasize favorable findings; and where and when findings should be published and by whom. Results We present extracts from internal company marketing assessments recommending that Pfizer and Parke-Davis (Pfizer acquired Parke-Davis in 2000 adopt a publication strategy to conduct trials and disseminate trial findings for unapproved uses rather than an indication strategy to obtain regulatory approval. We show internal company email correspondence and documents revealing how publication content was influenced and spin was applied; how the company selected where trial

  8. Implementation of a publication strategy in the context of reporting biases. A case study based on new documents from Neurontin® litigation

    Science.gov (United States)

    2012-01-01

    Background Previous studies have documented strategies to promote off-label use of drugs using journal publications and other means. Few studies have presented internal company communications that discussed financial reasons for manipulating the scholarly record related to off-label indications. The objective of this study was to build on previous studies to illustrate implementation of a publication strategy by the drug manufacturer for four off-label uses of gabapentin (Neurontin®, Pfizer, Inc.): migraine prophylaxis, treatment of bipolar disorders, neuropathic pain, and nociceptive pain. Methods We included in this study internal company documents, email correspondence, memoranda, study protocols and reports that were made publicly available in 2008 as part of litigation brought by consumers and health insurers against Pfizer for fraudulent sales practices in its marketing of gabapentin (see http://pacer.mad.uscourts.gov/dc/cgi-bin/recentops.pl?filename=saris/pdf/ucl%20opinion.pdf for the Court’s findings). We reviewed documents pertaining to 20 clinical trials, 12 of which were published. We categorized our observations related to reporting biases and linked them with topics covered in internal documents, that is, deciding what should and should not be published and how to spin the study findings (re-framing study results to explain away unfavorable findings or to emphasize favorable findings); and where and when findings should be published and by whom. Results We present extracts from internal company marketing assessments recommending that Pfizer and Parke-Davis (Pfizer acquired Parke-Davis in 2000) adopt a publication strategy to conduct trials and disseminate trial findings for unapproved uses rather than an indication strategy to obtain regulatory approval. We show internal company email correspondence and documents revealing how publication content was influenced and spin was applied; how the company selected where trial findings would be presented or

  9. Estimating the Clinical and Economic Impact of Maintaining use of 13-valent Pneumococcal Conjugate Vaccine (PCV13) in Mexico

    Science.gov (United States)

    Wasserman, Matt; Wilson, Michele; McDade, Cheryl; Grajales, Ana Gabriela; Palacios, Maria Gabriela; Baez- Revueltas, Fabiola Berenice; Farkouh, Raymond

    2017-01-01

    presented in MXN Conclusion Continued use of PCV13 in Mexico is predicted to provide greater public health benefit compared with switching to PCV10 not only economically but also socially. It is important that policy makers consider potential implications of disease re-emergence of non-covered serotypes when considering modifications to vaccination strategies. Disclosures M. Wasserman, Pfizer: Employee, Salary; M. Wilson, Pfizer: Consultant, Consulting fee; C. McDade, Pfizer: Consultant, Consulting fee; A. G. Grajales, Pfizer: Employee, Salary; M. G. Palacios, Pfizer: Employee, Salary; F. B. Baez- Revueltas, Pfizer: Employee, Salary; R. Farkouh, Pfizer: Employee, Salary.

  10. Development of Prescription Drug Information Leaflets: Impact of Cognitive Effort and Patient Involvement on Prescription Medication Information Processing.

    Science.gov (United States)

    Patel, Harshali K; Bapat, Shweta S; Bhansali, Archita H; Sansgiry, Sujit S

    2018-01-01

    The objective of this study was to develop a one-page (1-page) prescription drug information leaflet (PILs) and assess their impact on the information processing variables, across 2 levels of patient involvement. One-page PILs were developed using cognitive principles to lower mental effort and improve comprehension. An experimental, 3 × 2 repeated measures study was conducted to determine the impact of cognitive effort, manipulated using leaflet type on comprehension across 2 levels (high/low) of patient involvement. Adults (≥18 years) in a university setting in Houston were recruited for the study. Each participant was exposed to 3 different types of prescription drug information leaflet (the current practice, preexisting 1-page text-only, and 1-page PILs) for the 3 drugs (Celebrex, Ventolin HFA, Prezista) for a given involvement scenario. A prevalidated survey instrument was used to measure product knowledge, attitude toward leaflet, and intention to read. Multivariate analysis of variance indicated significant positive effect of cognitive effort, involvement, and their interaction effect across all measured variables. Mean scores for product knowledge, attitude toward leaflet, and intention to read were highest for PILs ( P information processing for consumers by reducing their cognitive effort.

  11. An Atomic Force Microscope Study Revealed Two Mechanisms in the Effect of Anticancer Drugs on Rate-Dependent Young's Modulus of Human Prostate Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Juan Ren

    Full Text Available Mechanical properties of cells have been recognized as a biomarker for cellular cytoskeletal organization. As chemical treatments lead to cell cytoskeletal rearrangements, thereby, modifications of cellular mechanical properties, investigating cellular mechanical property variations provides insightful knowledge to effects of chemical treatments on cancer cells. In this study, the effects of eight different anticancer drugs on the mechanical properties of human prostate cancer cell (PC-3 are investigated using a recently developed control-based nanoindentation measurement (CNM protocol on atomic force microscope (AFM. The CNM protocol overcomes the limits of other existing methods to in-liquid nanoindentation measurement of live cells on AFM, particularly for measuring mechanical properties of live cells. The Young's modulus of PC-3 cells treated by the eight drugs was measured by varying force loading rates over three orders of magnitude, and compared to the values of the control. The results showed that the Young's modulus of the PC-3 cells increased substantially by the eight drugs tested, and became much more pronounced as the force load rate increased. Moreover, two distinct trends were clearly expressed, where under the treatment of Disulfiram, paclitaxel, and MK-2206, the exponent coefficient of the frequency- modulus function remained almost unchanged, while with Celebrex, BAY, Totamine, TPA, and Vaproic acid, the exponential rate was significantly increased.

  12. Rosiglitazone: a disappointing DREAM.

    Science.gov (United States)

    Nissen, Steven

    2007-09-01

    Dr Steven Nissen is a heart specialist and currently holds the position of chairman of cardiovascular medicine at the Cleveland Clinic, OH, USA. His work has involved the development of miniaturised ultrasound imaging devices that can be threaded into a patient's heart that allow measurement of the size and composition of plaques, which indicate early artery damage. The ability to characterize and measure the size of plaques provided a novel, effective method to evaluate the efficacy of anticholesterol medications, and for the past two decades Dr Nissen has been using these and other techniques to examine the efficacy of drugs. He has also developed a strong interest in drug safety. His work linked COX-2 inhibitors such as Celebrex and Vioxx (Merck, NJ, USA) with heart attacks, and prevented Merck's similar product, Arcoxia, from being approved. He also highlighted the serious heart attack risk associated with the experimental drug Pargluva and the drug was subsequently not approved by the US FDA. More recently, Dr Nissen's work has focused on the drug rosiglitazone, which was shown to have high cardiovascular risks and has since been given a FDA warning. Here, Dr Nissen discusses the publication of the rosiglitazone meta-analysis and why he considers work in this area to be crucially important for patients.

  13. Preventive but Not Curative Efficacy of Celecoxib on Bladder Carcinogenesis in a Rat Model

    Directory of Open Access Journals (Sweden)

    José Sereno

    2010-01-01

    Full Text Available To evaluate the effect of a cyclooxygenase 2 inhibitor, celecoxib (CEL, on bladder cancer inhibition in a rat model, when used as preventive versus as curative treatment. The study comprised 52 male Wistar rats, divided in 5 groups, during a 20-week protocol: control: vehicle, carcinogen: 0.05% of N-butyl-N-(4-hydroxybutyl nitrosamine (BBN, CEL: 10 mg/kg/day of the selective COX-2 inhibitor Celebrex, preventive CEL (CEL+BBN-P, and curative CEL (BBN+CEL-C groups. Although tumor growth was markedly inhibited by the preventive application of CEL, it was even aggravated by the curative treatment. The incidence of gross bladder carcinoma was: control 0/8(0%, BBN 13/20(65%, CEL 0/8(0%, CEL+BBN-P 1/8(12.5%, and BBN+CEL-C 6/8(75%. The number and volume of carcinomas were significantly lower in the CEL+BBN-P versus BBN, accompanied by an ample reduction in hyperplasia, dysplasia, and papillary tumors as well as COX-2 immunostaining. In spite of the reduction of tumor volumes in the curative BBN+CEL-C group, tumor malignancy was augmented. An anti-inflammatory and antioxidant profile was encountered only in the group under preventive treatment. In conclusion, preventive, but not curative, celecoxib treatment promoted a striking inhibitory effect on bladder cancer development, reinforcing the potential role of chemopreventive strategies based on cyclooxygenase 2 inhibition.

  14. Improved Dissolution and Oral Bioavailability of Celecoxib by a Dry Elixir System.

    Science.gov (United States)

    Cho, Kwan Hyung; Jee, Jun-Pil; Yang, Da A; Kim, Sung Tae; Kang, Dongjin; Kim, Dae-Young; Sim, Taeyong; Park, Sang Yeob; Kim, Kyeongsoon; Jang, Dong-Jin

    2018-02-01

    The purpose of this study was to develop and evaluate a dry elixir (DE) system for enhancing the dissolution rate and oral bioavailability of celecoxib. DE system has been used for improving solubility, oral bioavailability of poorly water-soluble drugs. The encapsulated drugs or solubilized drugs in the matrix are rapidly dissolved due to the co-solvent effect, resting in both an enhanced dissolution and bioavailability. DEs containing celecoxib were prepared by spray-drying method and characterized by morphology, drug/ethanol content, drug crystallinity, dissolution rate and oral bioavailability. The ethanol content and drug content in DE system could be easily altered by controlling the spraydrying conditions. The dissolution profile of celecoxib from DE proved to be much higher than that of celecoxib powder due to the nano-structured matrix, amorphous state and encapsulated ethanol. The bioavailability of celecoxib from DEs was compared with celecoxib powder alone and commercial product (Celebrex®) in rats. In particular, blood concentrations of celecoxib form DE formulation were much greater than those of native celecoxib and market product. The data demonstrate that the DE system could provide an useful solid dosage form to enhance the solubility, dissolution rate and oral bioavailability of celecoxib.

  15. Warfarin Management and Outcomes in Patients with Nonvalvular Atrial Fibrillation Within an Integrated Health Care System.

    Science.gov (United States)

    An, JaeJin; Niu, Fang; Zheng, Chengyi; Rashid, Nazia; Mendes, Robert A; Dills, Diana; Vo, Lien; Singh, Prianka; Bruno, Amanda; Lang, Daniel T; Le, Paul T; Jazdzewski, Kristin P; Aranda, Gustavus

    2017-06-01

    times per year), or frequently adjusted warfarin dose (≥ 11 times per year) consistently showed poor TTRs (mean TTR for the highest quartiles was 45.3%-48.3%). A higher TTR was associated with a lower risk of clinical outcomes regardless of frequency of INR monitoring, pharmacist interventions, or number of dose adjustments. Patients whose TTRs were Company and Pfizer. Authors from Bristol-Myers Squibb Company and Pfizer participated in the design of the study, interpretation of the data, review/revision of the manuscript, and approval of the final version of the manuscript. An received a grant for research support from Bristol-Myers Squibb/Pfizer. Niu, Rashid, and Zheng received a grant from Bristol-Myers Squibb/Pfizer to their institutions for salary reimbursement. Vo, Singh, and Aranda are employed by Bristol-Myers Squibb; Bruno was employed by Bristol-Myers Squibb at the time of this study. Mendes and Dills are employed by Pfizer, and Mendes was a member of the Pfizer Cardiovascular and Metabolic Field Medical Team during the time of this study. Lang, Jazdzewski, and Le have no known conflicts of interest to report. Study concept and design were contributed primarily by An and Rashid, along with the other authors. Niu took the lead in data collection, along with Zheng, and data interpretation was performed by An, along with Mendes and Dills, with assistance from the other authors. The manuscript was written by An and revised by Mendes, Dills, Vo, Singh, Bruno, and Aranda, along with Lang, Le, and Jazdezewski. Part of this study's findings was presented at the CHEST 2015 Annual Meeting in Montreal, Canada, on October 28, 2015.

  16. How much cash does your company need?

    Science.gov (United States)

    Passov, Richard

    2003-11-01

    In late 2001, the directors of Pfizer asked that very question. And with good reason. After its 2000 merger with rival Warner-Lambert, the New York-based pharmaceutical giant found itself sitting on a net cash position of $8 billion, which seemed extraordinarily conservative for a company whose products generated $30 billion in revenues. Most large companies with revenues that healthy would increase leverage, thereby unlocking tremendous value for shareholders. But knowledge-intensive companies like Pfizer, this author argues, are in a class apart. Because their largely intangible assets (like R&D) are highly volatile and cannot easily be valued, they are more vulnerable to financial distress than are firms with a preponderance of tangible assets. To insure against that risk, they need to maintain large positive cash balances. These companies' decisions to run large cash balances is one of the key reasons their shares sustain consistent premiums. Only by investing in their intangible assets can knowledge-based companies hope to preserve the value of those assets. A company that finds itself unable to do so because unfavorable market conditions reduce its operating cash flows will see its share price suffer almost as much as if it were to default on its debts. By the same token, with the right balance sheet, knowledge companies can profitably insure against the risk of failing to sustain value-added investments in difficult times. An optimal capital structure that calls for significant cash balances is certainly at odds with the results of a traditional capital structure analysis, the author demonstrates, but it explains the financial policies of many well-run companies, from Pfizer to Intel to ChevronTexaco.

  17. Criptococose canina: relato de caso Canine ocular cryptococcosis: a case report

    Directory of Open Access Journals (Sweden)

    C.E. Larsson

    2003-10-01

    Full Text Available Descreve-se, pela primeira vez no Brasil, um caso de criptococose canina com acometimento oftalmo e dermatopático, com diagnóstico intra-vitam, em animal da raça Pastor Alemão, fêmea, com 24 meses de vida, criado em São Paulo, em contacto com outros cinco cães assintomáticos, que havia se infectado pelo contato com dejetos de pombos (Columba livia. Evoluia há 90 dias, com quadro tegumentar e ósseo, sintomas e lesões características, sendo, ainda, detectada forma assintomática de coriorretinite, de início unilateral. O diagnóstico foi estabelecido pelos dados da anamnese, dos exames físico, dermatológico e complementares (radiográfico, cultivo micológico, histopatologia de pele tendo-se evidenciado e isolado cepa de Criptococcus neoformans var. neoformans. Após nove meses de terapia com itraconazol (9mg/kg/SID/VO houve involução total do quadro, sem qualquer efeito adverso à droga.A case of cryptococcosis with ocular and cutaneous involvement is reported by the first time in Brazil in a dog. A two-year-old female German Shepherd living in a hold house with other five healthy dogs was infected through the contact with pigeon (Columba livia feces. The illness started 90 days previously with cutaneous and bone involvement resulting in characteristic clinical signs and lesions, in addition to a initially unilateral asymptomatic chorioretinitis. The diagnosis was established based on anamnesis, physical and dermatologic examinations and complementary exams (radiographs, skin biopsy and histopathology and the isolation of a Cryptococcus neoformans var. neoformans strain was accomplished. There was a complete resolution of the disease after nine months of therapy using itraconazole (9mg/kg, q24h, PO and no side effect was observed.

  18. The effect of renal diet in association with enalapril or benazepril on proteinuria in dogs with proteinuric chronic kidney disease

    Directory of Open Access Journals (Sweden)

    A. Zatelli

    2016-07-01

    Full Text Available Treating proteinuria in dogs reduces the progression of chronic kidney disease (CKD; renal diets and angiotensin-converting enzyme (ACE-inhibitors are cornerstones of treatment. Whether different ACE-inhibitors have distinct kidney protective effects is unknown; it is therefore hypothesized that renal diets and enalapril or benazepril have different beneficial effects in proteinuric CKD dogs. Forty-four dogs with proteinuric CKD (IRIS stages 1-4 were enrolled in the study and were fed renal diet for 30 days. Thereafter, they were randomly assigned to one of 2 groups. Dogs in group A (n=22 received enalapril (0.5 mg/kg, q12h and in group B (n=22 benazepril (0.5 mg/kg, q24h; in both groups, dogs were fed the same renal diet. After randomization, dogs were monitored for 120 days. Body weight and body condition score (BCS, serum concentrations of creatinine, blood urea nitrogen (BUN, albumin and total proteins, and urine protein-to-creatinine (UPC ratio were compared at different time-points. After 30 days of renal diet, creatinine, BUN and UPC ratio decreased significantly (p<0.0001. Compared to randomization, body weight, BCS, albumin, total proteins, creatinine and BUN did not vary during follow-up in the 44 dogs and differences between group A and B were not observed. However, the UPC ratio of group A at day 60, 90 and 150 was significantly lower than in group B and compared to randomization (p<0.05. In group B it did not vary overtime. It is concluded that the renal diet is beneficial to decrease creatinine, BUN and UPC ratio in proteinuric CKD dogs. Enalapril further ameliorates proteinuria if administered along with renal diet.

  19. Identification of Heterobilharzia americana infection in a dog residing in Indiana with no history of travel.

    Science.gov (United States)

    Rodriguez, Jessica Y; Camp, Joseph W; Lenz, Stephen D; Kazacos, Kevin R; Snowden, Karen F

    2016-04-01

    A 1-year-old castrated male dog residing in Indiana was examined because of intermittent vomiting of 4 months' duration. The dog's condition did not resolve with medication. Diagnostic imaging revealed a possible partial obstruction at the ileocecal junction. An exploratory laparotomy was performed. The jejunum contained diffusely distributed, nodular, intramural lesions; 2 biopsy specimens were collected from representative lesions. The pancreas was grossly swollen, and pancreatitis was presumed present. No other abnormalities were observed in the abdomen. Histologic examination of the submitted biopsy specimens revealed infection with Heterobilharzia americana. After diagnosis, the dog was treated with fenbendazole suspension (48 mg/kg [21.8 mg/lb], PO, q 24 h) for 10 days. This treatment was subsequently repeated 11 and 80 days later. One week after the end of the last fenbendazole treatment, several H americana eggs were detected in a fecal sample via saline sedimentation, and the dog was given praziquantel (25 mg/kg [11.4 mg/lb], PO, q 8 h) for 2 days. No gastrointestinal signs were evident 4 months after that treatment. The dog described in this report was the first autochthonous canine case of H americana infection in Indiana, to the authors' knowledge; this case has confirmed that the distribution of this parasite in the Midwestern United States is broader than previously known. Increased awareness of the distribution of H americana should aid veterinarians in early, noninvasive diagnosis and appropriate treatment of affected animals. Repeated treatments and recheck fecal examinations may be necessary when managing these cases.

  20. Effects of a single dose of enrofloxacin on body temperature and tracheobronchial neutrophil count in healthy Thoroughbreds premedicated with interferon-α and undergoing long-distance transportation.

    Science.gov (United States)

    Tsuchiya, Takeru; Hobo, Seiji; Endo, Yoshiro; Narita, Shoichi; Sakamoto, Koji

    2012-07-01

    To evaluate effects of a single dose of enrofloxacin (5 mg/kg, IV) on body temperature and tracheobronchial neutrophil count in healthy Thoroughbreds premedicated with interferon-α and undergoing long-distance transportation. 32 healthy Thoroughbreds. All horses received interferon-α (0.5 U/kg, sublingually, q 24 h) as an immunologic stimulant for 2 days before transportation and on the day of transportation. Horses were randomly assigned to receive enrofloxacin (5 mg/kg, IV, once; enrofloxacin group) or saline (0.9% NaCl) solution (50 mL, IV, once; control group) ≤ 1 hour before being transported 1,210 km via commercial vans (duration, approx 26 hours). Before and after transportation, clinical examination, measurement of temperature per rectum, and hematologic analysis were performed for all horses; a tracheobronchial aspirate was collected for neutrophil quantification in 12 horses (6/group). Horses received antimicrobial treatment after transportation if deemed necessary by the attending clinician. No adverse effects were associated with treatment. After transportation, WBC count and serum amyloid A concentration in peripheral blood samples and neutrophil counts in tracheobronchial aspirates were significantly lower in horses of the enrofloxacin group than in untreated control horses. Fever (rectal temperature, ≥ 38.5°C) after transportation was detected in 3 of 16 enrofloxacin group horses and 9 of 16 control horses; additional antimicrobial treatment was required in 2 horses in the enrofloxacin group and 7 horses in the control group. In horses premedicated with interferon-α, enrofloxacin appeared to provide better protection against fever and lower respiratory tract inflammation than did saline solution.

  1. Evaluation of the Efficacy and Safety of High Dose Short Duration Enrofloxacin Treatment Regimen for Uncomplicated Urinary Tract Infections in Dogs

    Science.gov (United States)

    Westropp, JL; Sykes, JE; Irom, S; Daniels, JB; Smith, A; Keil, D; Settje, T; Wang, Y; Chew, DJ

    2012-01-01

    Background Uncomplicated urinary tract infections (UTI) in dogs usually are treated with antimicrobial drugs for 10–14 days. Shorter duration antimicrobial regimens have been evaluated in human patients. Hypothesis A high dose short duration (HDSD) enrofloxacin protocol administered to dogs with uncomplicated UTI will not be inferior to a 14-day treatment regimen with amoxicillin-clavulanic acid. Animals Client-owned adult, otherwise healthy dogs with aerobic bacterial urine culture yielding ≥103 CFU/mL of bacteria after cystocentesis. Methods Prospective, multicenter, controlled, randomized blinded clinical trial. Enrolled dogs were randomized to group 1 (enrofloxacin 18–20 mg/kg PO q24h for 3 days) or group 2 (amoxicillin-clavulanic acid 13.75–25 mg/kg PO q12h for 14 days). Urine cultures were obtained at days 0, 10, and 21. Microbiologic and clinical cure rates were evaluated 7 days after antimicrobial treatment was discontinued. Lower urinary tract signs and adverse events also were recorded. Results There were 35 dogs in group 1 and 33 in group 2. The microbiologic cure rate was 77.1 and 81.2% for groups 1 and 2, respectively. The clinical cure rate was 88.6 and 87.9% for groups 1 and 2, respectively. Cure rates between groups did not differ according to the selected margin of noninferiority. Conclusions and Clinical Importance HDSD enrofloxacin treatment was not inferior to a conventional amoxicillin-clavulanic acid protocol for the treatment of uncomplicated bacterial UTI in dogs. Further research is warranted to determine if this protocol will positively impact owner compliance and decrease the emergence of antimicrobial resistance. PMID:22486931

  2. Activity of Daptomycin or Linezolid in Combination with Rifampin or Gentamicin against Biofilm-Forming Enterococcus faecalis or E. faecium in an In Vitro Pharmacodynamic Model Using Simulated Endocardial Vegetations and an In Vivo Survival Assay Using Galleria mellonella Larvae

    Science.gov (United States)

    Luther, Megan K.; Arvanitis, Marios; Mylonakis, Eleftherios

    2014-01-01

    Enterococci are the third most frequent cause of infective endocarditis. A high-inoculum stationary-phase in vitro pharmacodynamic model with simulated endocardial vegetations was used to simulate the human pharmacokinetics of daptomycin at 6 or 10 mg/kg of body weight/day or linezolid at 600 mg every 12 h (q12h), alone or in combination with gentamicin at 1.3 mg/kg q12h or rifampin at 300 mg q8h or 900 mg q24h. Biofilm-forming, vancomycin-susceptible Enterococcus faecalis and vancomycin-resistant Enterococcus faecium (vancomycin-resistant enterococcus [VRE]) strains were tested. At 24, 48, and 72 h, all daptomycin-containing regimens demonstrated significantly more activity (decline in CFU/g) than any linezolid-containing regimen against biofilm-forming E. faecalis. The addition of gentamicin to daptomycin (at 6 or 10 mg/kg) in the first 24 h significantly improved bactericidal activity. In contrast, the addition of rifampin delayed the bactericidal activity of daptomycin against E. faecalis, and the addition of rifampin antagonized the activities of all regimens against VRE at 24 h. Also, against VRE, the addition of gentamicin to linezolid at 72 h improved activity and was bactericidal. Rifampin significantly antagonized the activity of linezolid against VRE at 72 h. In in vivo Galleria mellonella survival assays, linezolid and daptomycin improved survival. Daptomycin at 10 mg/kg improved survival significantly over that with linezolid against E. faecalis. The addition of gentamicin improved the efficacy of daptomycin against E. faecalis and those of linezolid and daptomycin against VRE. We conclude that in enterococcal infection models, daptomycin has more activity than linezolid alone. Against biofilm-forming E. faecalis, the addition of gentamicin in the first 24 h causes the most rapid decline in CFU/g. Of interest, the addition of rifampin decreased the activity of daptomycin against both E. faecalis and VRE. PMID:24867993

  3. New dosing strategies for an old antibiotic: pharmacodynamics of front-loaded regimens of colistin at simulated pharmacokinetics in patients with kidney or liver disease.

    Science.gov (United States)

    Rao, Gauri G; Ly, Neang S; Haas, Curtis E; Garonzik, Samira; Forrest, Alan; Bulitta, Jurgen B; Kelchlin, Pamela A; Holden, Patricia N; Nation, Roger L; Li, Jian; Tsuji, Brian T

    2014-01-01

    Increasing evidence suggests that colistin monotherapy is suboptimal at currently recommended doses. We hypothesized that front-loading provides an improved dosing strategy for polymyxin antibiotics to maximize killing and minimize total exposure. Here, we utilized an in vitro pharmacodynamic model to examine the impact of front-loaded colistin regimens against a high bacterial density (10(8) CFU/ml) of Pseudomonas aeruginosa. The pharmacokinetics were simulated for patients with hepatic (half-life [t1/2] of 3.2 h) or renal (t1/2 of 14.8 h) disease. Front-loaded regimens (n=5) demonstrated improvement in bacterial killing, with reduced overall free drug areas under the concentration-time curve (fAUC) compared to those with traditional dosing regimens (n=14) with various dosing frequencies (every 12 h [q12h] and q24h). In the renal failure simulations, front-loaded regimens at lower exposures (fAUC of 143 mg · h/liter) obtained killing activity similar to that of traditional regimens (fAUC of 268 mg · h/liter), with an ∼97% reduction in the area under the viable count curve over 48 h. In hepatic failure simulations, front-loaded regimens yielded rapid initial killing by up to 7 log10 within 2 h, but considerable regrowth occurred for both front-loaded and traditional regimens. No regimen eradicated the high bacterial inoculum of P. aeruginosa. The current study, which utilizes an in vitro pharmacodynamic infection model, demonstrates the potential benefits of front-loading strategies for polymyxins simulating differential pharmacokinetics in patients with hepatic and renal failure at a range of doses. Our findings may have important clinical implications, as front-loading polymyxins as a part of a combination regimen may be a viable strategy for aggressive treatment of high-bacterial-burden infections.

  4. Diagnosis and treatment of Sarcocystis neurona-induced myositis in a free-ranging California sea lion.

    Science.gov (United States)

    Carlson-Bremer, Daphne P; Gulland, Frances M D; Johnson, Christine K; Colegrove, Kathleen M; Van Bonn, William G

    2012-02-01

    An underweight, lethargic adult female California sea lion (Zalophus californianus) became stranded along the California shore and was captured and transported to a rehabilitation hospital for assessment and care. Initial physical assessment revealed the sea lion was lethargic and in poor body condition. Active myositis was diagnosed on the basis of concurrent elevations in activities of alanine aminotransferase and creatine kinase detected during serum biochemical analysis. Infection with Sarcocystis neurona was diagnosed after serologic titers increased 4-fold over a 3-week period. Diagnosis was confirmed on the basis of histopathologic findings, positive results on immunohistochemical staining, and results of quantitative PCR assay on biopsy specimens obtained from the diaphragm and muscles of the dorsal cervical region. Anticoccidial treatment was instituted with ponazuril (10 mg/kg [4.5 mg/lb], PO, q 24 h) and continued for 28 days. Prednisone (0.2 mg/kg [0.09 mg/lb], PO, q 12 h) was administered for 2 days and then every 24 hours for 5 days to treat associated inflammation. At the end of treatment, the sea lion was clinically normal, alanine aminotransferase and creatine kinase values were within reference limits, and antibody titers against S neurona had decreased 6-fold. The sea lion was released approximately 3 months after becoming stranded. S neurona-induced myositis was diagnosed in a free-ranging California sea lion. On the basis of the successful treatment and release of this sea lion, anticoccidial treatment should be considered for marine mammals in which protozoal disease is diagnosed.

  5. Evaluation of cisplatin combined with piroxicam for the treatment of oral malignant melanoma and oral squamous cell carcinoma in dogs.

    Science.gov (United States)

    Boria, Pedro A; Murry, Daryl J; Bennett, Peter F; Glickman, Nita W; Snyder, Paul W; Merkel, Brenna L; Schlittler, Deborah L; Mutsaers, Anthony J; Thomas, Rose M; Knapp, Deborah W

    2004-02-01

    To determine the maximum tolerated dose (MTD) of cisplatin administered with piroxicam, the antitumor activity and toxicity of cisplatin combined with piroxicam in dogs with oral malignant melanoma (OMM) and oral squamous cell carcinoma (SCC), and the effects of piroxicam on the pharmacokinetics of cisplatin in dogs with tumors. Prospective nonrandomized clinical trial. 25 dogs. Dogs were treated with a combination of cisplatin (escalating dose with 6 hours of diuresis with saline [0.9% NaCI] solution) and piroxicam (0.3 mg/kg 10.14 mg/lb], PO, q 24 h). The initial cisplatin dose (50 mg/m2) was increased by 5 mg/m2 until the MTD was reached. Tumor stage and size were determined at 6-week intervals during treatment. The pharmacokinetics of cisplatin were determined in dogs receiving a combination of cisplatin and piroxicam during the clinical trial and dogs that were treated with cisplatin alone. 11 dogs with OMM and 9 dogs with SCC were included in the clinical trial. The MTD of cisplatin when administered in combination with piroxicam was 50 mg/m2. Tumor remission occurred in 5 of 9 dogs with SCC and 2 of 11 dogs with OMM. The most common abnormality observed was renal toxicosis. Clearance of cisplatin in dogs that were treated with cisplatin alone was not significantly different from that in dogs treated with a combination of cisplatin and piroxicam. Cisplatin administered in combination with piroxicam had antitumor activity against OMM and SCC. The level of toxicity was acceptable, although renal function must be monitored carefully.

  6. Diabetes mellitus remission in a cat with pituitary-dependent hyperadrenocorticism after trilostane treatment.

    Science.gov (United States)

    Muschner, Adriana Cunha; Varela, Fernanda Venzon; Hazuchova, Katarina; Niessen, Stijn Jm; Pöppl, Álan Gomes

    2018-01-01

    An 8-year-old male neutered Persian cat was presented with polyuria, polydipsia, polyphagia and muscle weakness associated with a 7 month history of diabetes mellitus (DM). The cat had initially been treated with neutral protamine Hagedorn (NPH) insulin 2 U q12h, followed by porcine lente insulin 2 U q12h and, most recently, 3 U glargine insulin q12h, without improvement of clinical signs. The cat also suffered from concurrent symmetrical bilateral alopecia of thorax and forelimbs, abdominal distension and lethargy. Hyperadrenocorticism (HAC), specifically pituitary-dependent HAC, was suspected and confirmed through abdominal ultrasonography demonstrating bilateral adrenal enlargement, and a low-dose dexamethasone suppression test using 0.1 mg/kg dexamethasone intravenously. Trilostane treatment (initially 10 mg/cat PO q24h then increased to 10 mg/cat PO q12h) was started and insulin sensitivity gradually improved, ultimately leading to diabetic remission after an increased in trilostane dose to 13mg/cat PO q12h, 14 months after the DM diagnosis and 7 months after the initiation of trilostane therapy. DM in cats with HAC is a difficult combination of diseases to treat. To our knowledge this is the first reported case of diabetic remission in a feline patient with HAC as a result of treatment with trilostane. Further work should focus on whether fine-tuning of trilostane-treatment protocols in cats with concurrent DM and HAC could lead to a higher proportion of diabetic remissions in this patient group.

  7. Age-dependent effects of systemic administration of oxytetracycline on the viscoelastic properties of rat tail tendons as a mechanistic basis for pharmacological treatment of flexural limb deformities in foals.

    Science.gov (United States)

    Wintz, Leslie R; Lavagnino, Michael; Gardner, Keri L; Sedlak, Aleksa M; Arnoczky, Steven P

    2012-12-01

    To describe the effect of systemically administered oxytetracycline on the viscoelastic properties of rat tail tendon fascicles (TTfs) to provide a mechanistic rationale for pharmacological treatment of flexural limb deformities in foals. TTfs from ten 1-month-old and ten 6-month-old male Sprague-Dawley rats. 5 rats in each age group were administered oxytetracycline (50 mg/kg, IP, q 24 h) for 4 days. The remaining 5 rats in each age group served as untreated controls. Five days after initiation of oxytetracycline treatment, TTfs were collected and their viscoelastic properties were evaluated via a stress-relaxation protocol. Maximum modulus and equilibrium modulus were compared via a 2-way ANOVA. Collagen fibril size, density, and orientation in TTfs were compared between treated and control rats. Viscoelastic properties were significantly decreased in TTfs from 1-month-old oxytetracycline-treated rats, compared with those in TTfs from 1-month-old control rats. Oxytetracycline had no effect on the viscoelastic properties of TTfs from 6-month-old rats. Collagen fibril size, density, and orientation in TTfs from 1-month-old rats did not differ between oxytetracycline-treated and control rats. Results confirmed that systemically administered oxytetracycline decreased the viscoelastic properties of TTfs from 1-month-old rats but not those of TTfs from 6-month-old rats. The decrease in viscoelastic properties associated with oxytetracycline treatment does not appear to be caused by altered collagen fibril diameter or organization. The age-dependent effect of oxytetracycline on the viscoelastic properties of tendons may be related to its effect on the maturation of the extracellular matrix of developing tendons.

  8. Diabetes mellitus remission in a cat with pituitary-dependent hyperadrenocorticism after trilostane treatment

    Science.gov (United States)

    Muschner, Adriana Cunha; Varela, Fernanda Venzon; Hazuchova, Katarina; Niessen, Stijn JM; Pöppl, Álan Gomes

    2018-01-01

    Case summary An 8-year-old male neutered Persian cat was presented with polyuria, polydipsia, polyphagia and muscle weakness associated with a 7 month history of diabetes mellitus (DM). The cat had initially been treated with neutral protamine Hagedorn (NPH) insulin 2 U q12h, followed by porcine lente insulin 2 U q12h and, most recently, 3 U glargine insulin q12h, without improvement of clinical signs. The cat also suffered from concurrent symmetrical bilateral alopecia of thorax and forelimbs, abdominal distension and lethargy. Hyperadrenocorticism (HAC), specifically pituitary-dependent HAC, was suspected and confirmed through abdominal ultrasonography demonstrating bilateral adrenal enlargement, and a low-dose dexamethasone suppression test using 0.1 mg/kg dexamethasone intravenously. Trilostane treatment (initially 10 mg/cat PO q24h then increased to 10 mg/cat PO q12h) was started and insulin sensitivity gradually improved, ultimately leading to diabetic remission after an increased in trilostane dose to 13mg/cat PO q12h, 14 months after the DM diagnosis and 7 months after the initiation of trilostane therapy. Relevance and novel information DM in cats with HAC is a difficult combination of diseases to treat. To our knowledge this is the first reported case of diabetic remission in a feline patient with HAC as a result of treatment with trilostane. Further work should focus on whether fine-tuning of trilostane-treatment protocols in cats with concurrent DM and HAC could lead to a higher proportion of diabetic remissions in this patient group. PMID:29707227

  9. Assessment of platelet function in healthy cats in response to commonly prescribed antiplatelet drugs using three point-of-care platelet function tests.

    Science.gov (United States)

    Ho, Kimberly K; Abrams-Ogg, Anthony Cg; Wood, R Darren; O'Sullivan, M Lynne; Kirby, Gordon M; Blois, Shauna L

    2017-06-01

    Objectives The objective was to determine if decreased platelet function could be detected after treatment with aspirin and/or clopidogrel in healthy cats using three point-of-care platelet function tests that evaluate platelet function by different methods: Multiplate (by impedance), Platelet Function Analyzer 100 (by mechanical aperture closure) and Plateletworks (by platelet counting). Methods Thirty-six healthy cats were randomly assigned to receive one of three oral treatments over an 8 day period: (1) aspirin 5 mg q72h; (2) aspirin 20.25 mg q72h; or (3) clopidogrel 18.75 mg q24h. Cats treated with 5 and 20.25 mg aspirin also received clopidogrel on days 4-8. Platelet aggregation in response to adenosine diphosphate and collagen ± arachidonic acid was assessed on days 1 (baseline), 4 and 8. Aspirin and clopidogrel metabolites were measured by high-performance liquid chromatography. Platelet function in response to treatment was analyzed by ANCOVA, linear regression and Spearman correlation. Results The only solitary aspirin effect was detected using Plateletworks with collagen in cats treated with 20.25 mg. The only effect detected by Multiplate was using arachidonic acid in cats treated with both aspirin 20.25 mg and clopidogrel. All clopidogrel treatment effects were detected by Platelet Function Analyzer 100, Plateletworks (adenosine diphosphate) and Plateletworks (collagen). Drug metabolites were present in all cats, but concentrations were minimally correlated to platelet function test results. Conclusions and relevance Platelet Function Analyzer 100 and Plateletworks using adenosine diphosphate ± collagen agonists may be used to detect decreased platelet function in response to clopidogrel treatment. Either aspirin is not as effective an antiplatelet drug as clopidogrel, or the tests used were not optimal to measure aspirin effect. Cats with heart disease are commonly prescribed antiplatelet drugs to decrease the risk of aortic thromboembolism

  10. Aldosterone breakthrough with benazepril in furosemide-activated renin-angiotensin-aldosterone system in normal dogs.

    Science.gov (United States)

    Lantis, A C; Ames, M K; Atkins, C E; DeFrancesco, T C; Keene, B W; Werre, S R

    2015-02-01

    Pilot studies in our laboratory revealed that furosemide-induced renin-angiotensin-aldosterone system (RAAS) activation was not attenuated by the subsequent co-administration of benazepril. This study was designed to evaluate the effect of benazepril on angiotensin-converting enzyme (ACE) activity and furosemide-induced circulating RAAS activation. Our hypothesis was that benazepril suppression of ACE activity would not suppress furosemide-induced circulating RAAS activation, indicated by urinary aldosterone concentration. Ten healthy hound dogs were used in this study. The effect of furosemide (2 mg/kg p.o., q12h; Group F; n = 5) and furosemide plus benazepril (1 mg/kg p.o., q24h; Group FB; n = 5) on circulating RAAS was determined by plasma ACE activity, 4-6 h posttreatment, and urinary aldosterone to creatinine ratio (UAldo:C) on days -1, -2, 1, 3, and 7. There was a significant increase in the average UAldo:C (μg/g) after the administration of furosemide (Group F baseline [average of days -1 and -2] UAldo:C = 0.41, SD 0.15; day 1 UAldo:C = 1.1, SD 0.56; day 3 UAldo:C = 0.85, SD 0.50; day 7 UAldo:C = 1.1, SD 0.80, P Benazepril suppressed ACE activity (U/L) in Group FB (Group FB baseline ACE = 16.4, SD 4.2; day 1 ACE = 3.5, SD 1.4; day 3 ACE = 1.6, SD 1.3; day 7 ACE = 1.4, SD 1.4, P Benazepril decreased plasma ACE activity but did not prevent furosemide-induced RAAS activation, indicating aldosterone breakthrough (escape). This is particularly noteworthy in that breakthrough is observed at the time of initiation of RAAS suppression, as opposed to developing after months of therapy. © 2014 John Wiley & Sons Ltd.

  11. The effect of renal diet in association with enalapril or benazepril on proteinuria in dogs with proteinuric chronic kidney disease.

    Science.gov (United States)

    Zatelli, A; Roura, X; D'Ippolito, P; Berlanda, M; Zini, E

    2016-01-01

    Treating proteinuria in dogs reduces the progression of chronic kidney disease (CKD); renal diets and angiotensin-converting enzyme (ACE)-inhibitors are cornerstones of treatment. Whether different ACE-inhibitors have distinct kidney protective effects is unknown; it is therefore hypothesized that renal diets and enalapril or benazepril have different beneficial effects in proteinuric CKD dogs. Forty-four dogs with proteinuric CKD (IRIS stages 1-4) were enrolled in the study and were fed renal diet for 30 days. Thereafter, they were randomly assigned to one of 2 groups. Dogs in group A (n=22) received enalapril (0.5 mg/kg, q12h) and in group B (n=22) benazepril (0.5 mg/kg, q24h); in both groups, dogs were fed the same renal diet. After randomization, dogs were monitored for 120 days. Body weight and body condition score (BCS), serum concentrations of creatinine, blood urea nitrogen (BUN), albumin and total proteins, and urine protein-to-creatinine (UPC) ratio were compared at different time-points. After 30 days of renal diet, creatinine, BUN and UPC ratio decreased significantly (p<0.0001). Compared to randomization, body weight, BCS, albumin, total proteins, creatinine and BUN did not vary during follow-up in the 44 dogs and differences between group A and B were not observed. However, the UPC ratio of group A at day 60, 90 and 150 was significantly lower than in group B and compared to randomization (p<0.05). In group B it did not vary overtime. It is concluded that the renal diet is beneficial to decrease creatinine, BUN and UPC ratio in proteinuric CKD dogs. Enalapril further ameliorates proteinuria if administered along with renal diet.

  12. Comparison of Efficacy of Long-term Oral Treatment with Telmisartan and Benazepril in Cats with Chronic Kidney Disease.

    Science.gov (United States)

    Sent, U; Gössl, R; Elliott, J; Syme, H M; Zimmering, T

    2015-01-01

    The efficacy and benefits of telmisartan in cats with chronic kidney disease (CKD) have not previously been reported. Long-term treatment of cats with CKD using telmisartan decreases urine protein-to-creatinine ratio (UP/C) similar to benazepril. Two-hundred and twenty-four client-owned adult cats with CKD. Prospective, multicenter, controlled, randomized, parallel group, blinded clinical trial with noninferiority design. Cats were allocated in a 1:1 ratio to either telmisartan (1 mg/kg; n = 112) or benazepril (0.5-1.0 mg/kg; n = 112) PO q24 h. The primary endpoint was prospectively defined as the change in proteinuria (benazepril:telmisartan) based on a log transformed weighted average of UP/C change from baseline (AUC 0→t/t) as a percentage compared using a confidence interval (CI) approach. Changes of UP/C from baseline were assessed on all study days and corrected for multiple comparisons. Telmisartan proved noninferior to benazepril in controlling proteinuria (CI, -0.035 to 0.268). At Day 180, UP/C compared to baseline in the telmisartan group was significantly lower (-0.05 ± 0.31; P = .016), whereas in the benazepril group the change (-0.02 ± 0.48) was not statistically significant (P = .136). Similar results were obtained at all assessment points with significant decrease in UP/C occurring with telmisartan but not benazepril. Both telmisartan and benazepril were well tolerated and safe. Telmisartan proved to be noninferior to benazepril and significantly decreased proteinuria relative to baseline at all assessment points whereas benazepril did not. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  13. Comparison of a single dose of moxidectin and a five-day course of fenbendazole to reduce and suppress cyathostomin fecal egg counts in a herd of embryo transfer-recipient mares.

    Science.gov (United States)

    Mason, Maren E; Voris, Nathan D; Ortis, Hunter A; Geeding, Amy A; Kaplan, Ray M

    2014-10-15

    To compare larvicidal regimens of fenbendazole and moxidectin for reduction and suppression of cyathostomin fecal egg counts (FEC) in a transient herd of embryo transfer-recipient mares. Randomized, complete block, clinical trial. 120 mares from 21 states, residing on 1 farm. An initial fecal sample was collected from each mare; mares with an FEC ≥ 200 eggs/g were assigned to treatment groups. Eighty-two horses received fenbendazole (10.0 mg/kg [4.5 mg/lb], PO, q 24 h for 5 days) or moxidectin (0.4 mg/kg [0.18 mg/lb], PO, once); FEC data were analyzed 14, 45, and 90 days after treatment. Mean FEC reduction was 99.9% for moxidectin-treated mares and 41.9% for fenbendazole-treated mares 14 days after treatment. By 45 days, mean FEC of fenbendazole-treated mares exceeded pretreatment counts; however, FECs of moxidectin-treated mares remained suppressed below pretreatment values for the duration of the 90-day study. Fecal egg counts were significantly different between groups at 14, 45, and 90 days after treatment. Failure of the 5-day regimen of fenbendazole to adequately reduce or suppress FEC suggested inadequate adulticidal and larvicidal effects. In contrast, a single dose of moxidectin effectively reduced and suppressed FEC for an extended period. Given the diverse geographic origins of study mares, these results are likely representative of cyathostomin-infected mares in much of the United States, confirming previous findings indicating that fenbendazole resistance in cyathostomins is widespread and that moxidectin remains an effective treatment for control of these important parasites.

  14. Lungworm (Crenosoma vulpis) infection in dogs on Prince Edward Island.

    Science.gov (United States)

    Bihr, T; Conboy, G A

    1999-01-01

    Crenosoma vulpis is a nematode lungworm that is highly prevalent in the red fox population of Atlantic Canada. Dogs are susceptible to infection with clinical signs consisting primarily of a chronic cough. A recent report of C. vulpis infection in 3 dogs on Prince Edward Island prompted an investigation into the importance of this parasite as a cause of chronic respiratory disease in Island dogs. A general prevalence was determined through the necropsy of dogs euthanized at the local humane society. Lungs were removed and examined for parasites using a lung flush technique. Rectal feces was collected and examined for first-stage larvae using the Baermann technique and zinc sulfate centrifugal flotation. Ten of 310 dogs (3.2%) were positive with 0-35 worms (mean = 11.0 +/- 13.4) recovered. First-stage larvae of C. vulpis were recovered in the rectal feces of the one animal in which no worms were recovered on lung flush. A second survey was conducted examining fecal samples with the Baermann technique from afebrile dogs with presenting signs of chronic cough that had no history of recent anthelmintic treatment and showed no signs of cardiac disease, based on physical examination. Fifteen of 55 dogs examined (27.3%) were definitively diagnosed as C. vulpis-positive. All of the infected dogs were treated with fenbendazole (50 mg/kg body weight, p.o. q24 h for 3-7 days). Clinical signs resolved in all of the dogs and fecal samples were negative 2-4 weeks posttreatment. It was concluded that C. vulpis infection was a significant cause of upper respiratory disease in dogs on Prince Edward Island and should be considered in all dogs with presenting signs of chronic cough. Images Figure 1. Figure 2. PMID:12001335

  15. A Phase I study evaluating the effect of age and weight on the pharmacokinetics of an injectable formulation of diclofenac solubilized with hydroxypropyl-β-cyclodextrin

    OpenAIRE

    Goldwater R; Kramer WG; Hamilton DA; Lang E; Wang J; Madden DE; Lacouture PG; Ramaiya A; Carr DB

    2016-01-01

    Ronald Goldwater,1 William G Kramer,2 Douglas A Hamilton,3,4 Eric Lang,4,5 Jianyuan Wang,4 Donna E Madden,4 Peter G Lacouture,6,7 Atulkumar Ramaiya,8 Daniel B Carr4,9 1PAREXEL International, Baltimore, MD, 2Kramer Consulting, LLC, North Potomac, MD, 3New Biology Ventures, LLC, San Mateo, CA, 4Javelin Pharmaceuticals, Cambridge, MA (now Hospira, a Pfizer company, Lake Forest, IL, USA), 5Covance, Princeton, NJ, 6Magidom Discovery, LLC, Lindenhurst, IL, 7Brown University School of Medicine, Prov...

  16. Therapeutic Efficacy and Safety of GH in Japanese Children with Down Syndrome Short Stature Accompanied by GH Deficiency

    OpenAIRE

    Meguri, Kyoko; Inoue, Masaru; Narahara, Koji; Sato, Takahiro; Takata, Ami; Ohki, Nobuhiko; Ozono, Keiichi

    2013-01-01

    In this study, we investigated the effects of GH treatment in children with Down syndrome who had been diagnosed with GH deficiency (GHD). A total of 20 subjects were investigated in this study. Fourteen Down syndrome children (5 boys and 9 girls) with short stature due to GHD were treated with GH at Okayama Red Cross General Hospital, and 6 Down syndrome children (4 boys and 2 girls) with short stature due to GHD were registered in the Pfizer International Growth Database (KIGS). Height SD s...

  17. Burden of disease from atrial fibrillation in adults from seven countries in Latin America

    Directory of Open Access Journals (Sweden)

    Cubillos L

    2014-09-01

    Full Text Available Luz Cubillos,1 Alexandra Haddad,2 Andreas Kuznik,3 Joaquin Mould-Quevedo41Medical Affairs, Pfizer Inc., New York, NY, USA; 2Gerente Médico Portafolio Cardiovascular, Dirección Médica, Pfizer Mexico, Mexico City, Mexico; 3Global Health Economics and Outcomes Research, Pfizer Inc., New York, NY, USA; 4Health Economics and Outcomes Research, Latin America and Primary Care, Pfizer Inc., New York, NY, USA The affiliations given here are those from at the time the research was done.Background: While some international studies have published epidemiologic overviews of atrial fibrillation (AF for the Latin America region, detailed data at the national level are lacking. The aim of this study was to estimate the burden of disease and morbidity associated with AF in adults over 40 years of age in Argentina, Brazil, Chile, Colombia, Mexico, Peru, and Venezuela.Methods: National healthcare system databases for each country in the analysis were used to identify cases of AF during 2010 based on ICD-10 codes. Patient comorbidities and treatment patterns in each country were assessed based on available data and extrapolation from relevant published information where local data were incomplete or unavailable. The prevalence of AF in each country was estimated using country-specific, national census data, and assumptions based on a review of the available literature.Results: Patients in outpatient or hospital care represented over half of the estimated total cases of AF, of whom around 60% were treated as outpatients. Across the seven countries analyzed, 74.5% of AF cases were adults ≥60 years old. However, with increasing age, the proportion of individuals with AF receiving treatment within the national healthcare systems decreased overall across all seven countries. The most commonly reported comorbidities associated with AF included arterial hypertension (51%–57%, heart failure (14.5%–30%, diabetes (12%–36.5%, and stroke (3%–12.7%.Conclusion

  18. Computer Models Simulate Fine Particle Dispersion

    Science.gov (United States)

    2010-01-01

    Through a NASA Seed Fund partnership with DEM Solutions Inc., of Lebanon, New Hampshire, scientists at Kennedy Space Center refined existing software to study the electrostatic phenomena of granular and bulk materials as they apply to planetary surfaces. The software, EDEM, allows users to import particles and obtain accurate representations of their shapes for modeling purposes, such as simulating bulk solids behavior, and was enhanced to be able to more accurately model fine, abrasive, cohesive particles. These new EDEM capabilities can be applied in many industries unrelated to space exploration and have been adopted by several prominent U.S. companies, including John Deere, Pfizer, and Procter & Gamble.

  19. Prebiotic Potential of Polydextrose

    Science.gov (United States)

    Stowell, Julian D.

    Polydextrose is a randomly bonded polymer of glucose with some sorbitol end-groups. It was originally developed by scientists at Pfizer seeking a low calorie bulking agent to be used in conjunction with intense sweeteners. Polydextrose has been used for more than 25 years in human food and beverage products around the world. It is currently marketed by Danisco A/S as Litesse®Two and Litesse®UltraTM and by A E Staley as Sta-Lite III.

  20. Interscience Conference on Antimicrobial Agents and Chemotherapy--49th annual meeting. Part 2. 12-15 September 2009, San Francisco, CA, USA.

    Science.gov (United States)

    Turner, Ben; Murch, Lisa

    2009-11-01

    The Interscience Conference on Antimicrobial Agents and Chemotherapy held in San Francisco included topics covering new therapeutic developments for the treatment of infectious diseases. This conference report highlights selected presentations on several antibiotics in development including a broad-spectrum penem beta-lactam antibiotic, a novel siderophore monobactam, as well as other novel antibiotics. Investigational drugs discussed include sulopenem and sulopenem etzadroxil (both Pfizer Inc), BAL-30072 (Basilea Pharmaceutica International Ltd), TP-120 and TP-787 (both Tetraphase Pharmaceuticals Inc), NAI-107 (New Anti Infectives Consortium/NexThera Biosciences) and ABI-200 (AdRem Biotech/US Department of Agriculture).

  1. Drug tendering: drug supply and shortage implications for the uptake of biosimilars

    Directory of Open Access Journals (Sweden)

    Dranitsaris G

    2017-09-01

    Full Text Available George Dranitsaris,1 Ira Jacobs,2 Carol Kirchhoff,3 Robert Popovian,4 Lesley G Shane5 1Augmentium Pharma Consulting Inc., Toronto, ON, Canada; 2Global Medical Affairs, Pfizer Inc, New York, NY, 3Global Technology Services, Biotechnology and Aseptic Sciences Group, Pfizer Inc, Chesterfield, MO, 4US Government Relations, Pfizer Inc, Washington, DC, 5Outcomes and Evidence, Global Health and Value, Pfizer Inc, New York, NY, USA Abstract: Due to the continued increase in global spending on health care, payers have introduced a number of programs, policies, and agreements on pharmaceutical pricing in order to control costs. While incentives to increase generic drug use have achieved significant savings, other cost-containment measures are required. Tendering is a formal procedure to purchase medications using competitive bidding for a particular contract. Although useful for cost containment, tendering can lead to decreased competition in a given market. Consequently, drug shortages can occur, resulting in changes to treatment plans to products that may have lower efficacy and/or an increased risk of adverse effects. Therefore, care must be taken to ensure that tendering does not negatively impact patient care or the health care system. A large and expanding portion of total pharmaceutical expenditure is for biologic therapies. These agents have revolutionized the treatment of many diseases, including cancer and inflammatory conditions; however, patient access to biologic drugs can be limited due to availability, insurance coverage, and cost. As branded biologic therapies reach the end of patent- and data-protection periods, biosimilars are being approved as lower-cost alternatives. Biosimilars are products that are highly similar to the originator product with no clinically meaningful differences in terms of safety, purity, or potency. As more biosimilars receive regulatory approval and adoption increases, these therapies are expected to have an

  2. Measurements of dose distribution in thyroids, gonads, crystalline and other organs, for radio-diagnostics with computorized tomography

    International Nuclear Information System (INIS)

    Coelho, M.J.

    1983-01-01

    An evaluation of radiation doses in organs, from radiologic examinations by computorized tomography was done, comparing with theoretic data obtained by Monte Carlo method. The measurements were done with help of a 'Rando Alderson Phantom' exposed to irradiation coming from a 0450 AS and E Pfizer Tomographic. The cases under study were the head and abdomen examinations. The dose assessment was done by using mini TLD's of LiF. The calculated dose equivalents were obtained by using the Monte Carlo method applied to a mathematical antropomorphic phantom, simulating the same experimental arrangements. The results were compared with the experimental one. (E.G.) [pt

  3. Exposure to gonads and eyes due to computerised tomography for brain scanning

    International Nuclear Information System (INIS)

    Pin-Chieh Hsu; Pao-Shan Weng; Ling-Nah Su

    1986-01-01

    Eye and gonad doses for some 150 patients were determined using thermoluminescence dosemeters. Doses received during CT scanning using a Toshiba scanner were compared with those obtained using a Pfizer scanner. A female Rando phantom was also used as the reference. For males, the average eye dose for the Toshiba was 1695+-2041 μGy per slice and the gonad dose was 2.0+-1.5 μGy per slice; for females it was 1953+-1923 μGy per slice for eyes and 0.4+-0.3 μGy per slice for gonads. (author)

  4. Effect of P2X(7) receptor knockout on exocrine secretion of pancreas, salivary glands and lacrimal glands

    DEFF Research Database (Denmark)

    Novak, Ivana; Jans, Ida M; Wohlfahrt, Louise

    2010-01-01

    the P2X(7) receptors affect fluid secretion in pancreas, salivary glands and tear glands. We monitored gland secretions in in vivo preparations of wild-type and P2X(7)(-/-) (Pfizer) mice stimulated with pilocarpine. In cell preparations from pancreas, parotid and lacrimal glands we measured ATP release...... and intracellular Ca(2+) activity using Fura-2. The data showed that pancreatic secretion and salivary secretions were reduced in P2X(7)(-/-) mice, and in contrast, tear secretion was increased in P2X(7)(-/-) mice. The secretory phenotype was also dependent on the sex of the animal, such that males were more...

  5. In Vitro Assembly of Virus-Like Particles of a Gammaretrovirus, the Murine Leukemia Virus XMRV

    Czech Academy of Sciences Publication Activity Database

    Hadravová, Romana; de Marco, A.; Ulbrich, P.; Štokrová, Jitka; Doležal, Michal; Pichová, Iva; Ruml, T.; Briggs, J. A. G.; Rumlová, Michaela

    2012-01-01

    Roč. 86, č. 3 (2012), s. 1297-1306 ISSN 0022-538X R&D Projects: GA ČR GA204/09/1388; GA MŠk 1M0508 Grant - others:GA MŠk(CZ) 1M0520 Program:1M Institutional research plan: CEZ:AV0Z40550506 Keywords : human-immunodeficiency-virus * Rous sarcoma virus * chronic-fatigue-syndrome * Pfizer monkey virus * N-terminal domain Subject RIV: CE - Biochemistry Impact factor: 5.076, year: 2012

  6. Flexible segments modulate co-folding of dUTPase and nucleocapsid proteins

    Czech Academy of Sciences Publication Activity Database

    Németh-Pongrácz, V.; Barabás, O.; Fuxreiter, M.; Simon, I.; Pichová, Iva; Rumlová, Michaela; Zábranská, Helena; Svergun, D.; Petoukhov, M.; Harmat, V.; Klement, E.; Hunyadi-Gulyás, E.; Medzihradszky, K. F.; Kónya, E.; Vértessy, B. G.

    2007-01-01

    Roč. 35, č. 2 (2007), s. 495-505 ISSN 0305-1048 R&D Projects: GA MŠk 1M0508 Grant - others:6th Framework Programme(XE) LSHC-CT-2005-012127 Institutional research plan: CEZ:AV0Z40550506 Source of funding: R - rámcový projekt EK Keywords : dUTPase * Mason-Pfizer monkey virus * structure * fusion protein NC-dUTPase Subject RIV: CE - Biochemistry Impact factor: 6.954, year: 2007

  7. Determinação de amlodipina atraves da tecnica LC-MS-MS em estudo de bioequivalencia

    OpenAIRE

    Andreia Maria Lopes Guermani Orives

    2004-01-01

    Resumo: O objetivo deste estudo foi avaliar a bioequivalência de duas formulações de amlodipina em comprimidos ( Amlodipina® 5 mg comprimidos, Laboratório Teuto Brasileiro Ltda., formulação teste e Norvasc ® 5 mg, Laboratórios Pfizer Ltda., como referência ) após administração oral a 24 voluntários adultos sadios de ambos os sexos. O estudo foi aberto, randomizado com duas fases, onde os voluntários receberam uma dose única de besilato de amlodipina 5 mg. As amostras de plasma foram obtidas e...

  8. Inhibition of HERG potassium channels by celecoxib and its mechanism.

    Directory of Open Access Journals (Sweden)

    Roman V Frolov

    Full Text Available Celecoxib (Celebrex, a widely prescribed selective inhibitor of cyclooxygenase-2, can modulate ion channels independently of cyclooxygenase inhibition. Clinically relevant concentrations of celecoxib can affect ionic currents and alter functioning of neurons and myocytes. In particular, inhibition of Kv2.1 channels by celecoxib leads to arrhythmic beating of Drosophila heart and of rat heart cells in culture. However, the spectrum of ion channels involved in human cardiac excitability differs from that in animal models, including mammalian models, making it difficult to evaluate the relevance of these observations to humans. Our aim was to examine the effects of celecoxib on hERG and other human channels critically involved in regulating human cardiac rhythm, and to explore the mechanisms of any observed effect on the hERG channels.Celecoxib inhibited the hERG, SCN5A, KCNQ1 and KCNQ1/MinK channels expressed in HEK-293 cells with IC(50s of 6.0 µM, 7.5 µM, 3.5 µM and 3.7 µM respectively, and the KCND3/KChiP2 channels expressed in CHO cells with an IC(50 of 10.6 µM. Analysis of celecoxib's effects on hERG channels suggested gating modification as the mechanism of drug action.The above channels play a significant role in drug-induced long QT syndrome (LQTS and short QT syndrome (SQTS. Regulatory guidelines require that all new drugs under development be tested for effects on the hERG channel prior to first administration in humans. Our observations raise the question of celecoxib's potential to induce cardiac arrhythmias or other channel related adverse effects, and make a case for examining such possibilities.

  9. Ruxolitinib synergizes with DMF to kill via BIM+BAD-induced mitochondrial dysfunction and via reduced SOD2/TRX expression and ROS.

    Science.gov (United States)

    Tavallai, Mehrad; Booth, Laurence; Roberts, Jane L; McGuire, William P; Poklepovic, Andrew; Dent, Paul

    2016-04-05

    We determined whether the myelofibrosis drug ruxolitinib, an inhibitor of Janus kinases 1/2 (JAK1 and JAK2), could interact with the multiple sclerosis drug dimethyl-fumarate (DMF) to kill tumor cells; studies used the in vivo active form of the drug, mono-methyl fumarate (MMF). Ruxolitinib interacted with MMF to kill brain, breast, lung and ovarian cancer cells, and enhanced the lethality of standard of care therapies such as paclitaxel and temozolomide. MMF also interacted with other FDA approved drugs to kill tumor cells including Celebrex® and Gilenya®. The combination of [ruxolitinib + MMF] inactivated ERK1/2, AKT, STAT3 and STAT5; reduced expression of MCL-1, BCL-XL, SOD2 and TRX; increased BIM expression; decreased BAD S112 S136 phosphorylation; and enhanced pro-caspase 3 cleavage. Expression of activated forms of STAT3, MEK1 or AKT each significantly reduced drug combination lethality; prevented BAD S112 S136 dephosphorylation and decreased BIM expression; and preserved TRX, SOD2, MCL-1 and BCL-XL expression. The drug combination increased the levels of reactive oxygen species in cells, and over-expression of TRX or SOD2 prevented drug combination tumor cell killing. Over-expression of BCL-XL or knock down of BAX, BIM, BAD or apoptosis inducing factor (AIF) protected tumor cells. The drug combination increased AIF : HSP70 co-localization in the cytosol but this event did not prevent AIF : eIF3A association in the nucleus.

  10. Cyclooxygenases 1 and 2 differentially regulate blood pressure and cerebrovascular responses to acute and chronic intermittent hypoxia: implications for sleep apnea.

    Science.gov (United States)

    Beaudin, Andrew E; Pun, Matiram; Yang, Christina; Nicholl, David D M; Steinback, Craig D; Slater, Donna M; Wynne-Edwards, Katherine E; Hanly, Patrick J; Ahmed, Sofia B; Poulin, Marc J

    2014-05-09

    Obstructive sleep apnea (OSA) is associated with increased risk of cardiovascular and cerebrovascular disease resulting from intermittent hypoxia (IH)-induced inflammation. Cyclooxygenase (COX)-formed prostanoids mediate the inflammatory response, and regulate blood pressure and cerebral blood flow (CBF), but their role in blood pressure and CBF responses to IH is unknown. Therefore, this study's objective was to determine the role of prostanoids in cardiovascular and cerebrovascular responses to IH. Twelve healthy, male participants underwent three, 6-hour IH exposures. For 4 days before each IH exposure, participants ingested a placebo, indomethacin (nonselective COX inhibitor), or Celebrex(®) (selective COX-2 inhibitor) in a double-blind, randomized, crossover study design. Pre- and post-IH blood pressure, CBF, and urinary prostanoids were assessed. Additionally, blood pressure and urinary prostanoids were assessed in newly diagnosed, untreated OSA patients (n=33). Nonselective COX inhibition increased pre-IH blood pressure (P ≤ 0.04) and decreased pre-IH CBF (P=0.04) while neither physiological variable was affected by COX-2 inhibition (P ≥ 0.90). Post-IH, MAP was elevated (P ≤ 0.05) and CBF was unchanged with placebo and nonselective COX inhibition. Selective COX-2 inhibition abrogated the IH-induced MAP increase (P=0.19), but resulted in lower post-IH CBF (P=0.01). Prostanoids were unaffected by IH, except prostaglandin E2 was elevated with the placebo (P=0.02). Finally, OSA patients had elevated blood pressure (P ≤ 0.4) and COX-1 formed thromboxane A2 concentrations (P=0.02). COX-2 and COX-1 have divergent roles in modulating vascular responses to acute and chronic IH. Moreover, COX-1 inhibition may mitigate cardiovascular and cerebrovascular morbidity in OSA. www.clinicaltrials.gov. Unique identifier: NCT01280006.

  11. Pharma TARP: A Troubled Asset Relief Program for Novel, Abandoned Projects in the Pharmaceutical Industry

    Directory of Open Access Journals (Sweden)

    Tamas Bartfai

    2011-01-01

    Full Text Available Within days of each other, Pfizer, Merck, and GlaxoSmithKline announced that they will focus on a few therapeutic areas only and abandon others entirely. Pfizer alone will close well over a hundred drug development projects that have reached two-thirds of the way to launch. The programs are deemed to be too risky and not lucrative enough for Big Pharma in the current climate. Society has a real need for the drugs that are no longer going to be developed for, among others, drug-resistant epilepsy, neuropathic and cancer pain, type-2 diabetes, obesity, and schizophrenia. The authors propose a radical response by the U.S. government and the National Institutes of Health to rescue these abandoned projects, and to continue selected programs for drug approval by the U.S. Food and Drug Administration and the European Medicines Agency. The investment required is small compared to the Troubled Asset Relief Program bank bail out, but the return on investment in financial terms and in satisfying societal needs makes this proposal attractive.

  12. Asbestos information clearinghouse. Hearing before the Subcommittee on Commerce, Transportation, and Tourism, Committee on Energy and Commerce, House of Representatives, Ninety-Ninth Congress, Second Session on H. R. 5078, July 17, 1986

    Energy Technology Data Exchange (ETDEWEB)

    1986-01-01

    Representatives of US Gypsum Co., Pfizer Inc., and the Environmental Protection Agency (EPA) testified on the Asbestos Information Clearinghouse Act of 1986 (H.R. 5078), which calls for an information center with samples of materials containing asbestos to simplify the task of identifying their characteristics. The goal of the bill is to make judiciary processes more efficient. EPA opposes the bill on the grounds that the rulemaking and collection of samples from building owners and asbestos manufacturers and processors for analysis would shift the inefficiency from the judiciary arena to EPA. EPA argued that the identification of defendants is a private-sector issue, and that the activities that would be assigned to EPA would be outside its mission. Pfizer supported the legislation, while the spokesman for US Gypsum pointed out that if the purpose is to remove those defendants from litigation who are not involved, extensive sampling would be a waste of time. Additional material submitted for the record follows the text of H.R. 5078 and the testimony of four witnesses.

  13. Interspecies radioimmunoassay for the major structural proteins of primate type-D retroviruses

    International Nuclear Information System (INIS)

    Colcher, D.; Teramoto, Y.A.; Schlom, J.

    1977-01-01

    A competition radioimmunoassay has been developed in which type-D retroviruses from three primate species compete. The assay utilizes the major structural protein (36,000 daltons) of the endogenous squirrel monkey retrovirus and antisera directed against the major structural protein (27,000 daltons) of the Mason-Pfizer monkey virus isolated from rhesus monkeys. Purified preparations of both viruses grown in heterologous cells, as well as extracts of heterologous cells infected with squirrel monkey retrovirus or Mason-Pfizer monkey virus, compete completely in the assay. Addition of an endogenous virus of the langur monkey also results in complete blocking. No blocking in the assay is observed with type-C baboon viruses, woolly monkey virus, and gibbon virus. Various other type-C and type-B viruses also showed no reactivity. An interspecies assay has thus been developed that recognizes the type-D retroviruses from both Old World monkey (rhesus and langur) and New World monkey (squirrel) species

  14. Surveillance and management of estrous cycle in Awassi and Lacaune ewes during out of season

    Directory of Open Access Journals (Sweden)

    Liviu Bogdan

    2016-11-01

    Full Text Available The purpose of this study was to increase fertility in sheep by applying modern biotechnology: induction and synchronization of estrous in non- breeding season. The ewes were divided into 3 equal batches. In all batches intravaginal sponge (Veramix/Intervet containing 60 mg of MPA was left in the vagina for 14 days. Immediately after removal of the sponge an injections of prostaglandin (Dinolytic/Pfizer at the dose of 12.5 mg (2,5ml/animal was administered in batch II. Batch III received two injections: PMSG hormone (Folligon/Intervet at the dose of 500 IU/animal and prostaglandin (Dinolytic/Pfizer at the dose of 12.5 mg (2,5 ml/animal. The research focused on several directions: assessment of estrous manifestation; occurrence of estrous interval after completion of hormonal therapy; duration of estrous; appreciation of gestation after the first and second estrous clinically manifested; percentage of fecundity. From the results obtained it follows that induction and synchronization of estrous in non-breeding season showed economic advantages by shortening the time needed for the installation of gestation, the possibility of lambing distribution, preparation and organization of mating.

  15. Drug–drug interactions involving antidepressants: focus on desvenlafaxine

    Directory of Open Access Journals (Sweden)

    Low Y

    2018-02-01

    Full Text Available Yvette Low,1 Sajita Setia,2 Graca Lima3 1Department of Pharmacy, National University of Singapore, Singapore; 2Medical Affairs, Pfizer Pte. Ltd., Singapore; 3Global Medical Affairs, Asia-Pacific Region, Pfizer, Hong Kong Abstract: Psychiatric and physical conditions often coexist, and there is robust evidence that associates the frequency of depression with single and multiple physical conditions. More than half of patients with depression may have at least one chronic physical condition. Therefore, antidepressants are often used in cotherapy with other medications for the management of both psychiatric and chronic physical illnesses. The risk of drug–drug interactions (DDIs is augmented by complex polypharmacy regimens and extended periods of treatment required, of which possible outcomes range from tolerability issues to lack of efficacy and serious adverse events. Optimal patient outcomes may be achieved through drug selection with minimal potential for DDIs. Desvenlafaxine is a serotonin–norepinephrine reuptake inhibitor approved for the treatment of adults with major depressive disorder. Pharmacokinetic studies of desvenlafaxine have shown a simple metabolic profile unique among antidepressants. This review examines the DDI profiles of antidepressants, particularly desvenlafaxine, in relation to drugs of different therapeutic areas. The summary and comparison of information available is meant to help clinicians in making informed decisions when using desvenlafaxine in patients with depression and comorbid chronic conditions. Keywords: desvenlafaxine, polypharmacy, comorbidities, depression, pharmacokinetics

  16. Nonadherence to statins: individualized intervention strategies outside the pill box

    Directory of Open Access Journals (Sweden)

    Lansberg P

    2018-05-01

    Full Text Available Peter Lansberg,1 Andre Lee,2 Zhen-Vin Lee,3 Kannan Subramaniam,4 Sajita Setia5 1Department of Pediatrics, University Medical Center, Groningen, the Netherlands; 2Department of Pharmacy, National University of Singapore, Singapore; 3Cardiology Unit, Department of Medicine, University Malaya Medical Centre, Kuala Lumpur, Malaysia; 4Global Medical Affairs, Asia-Pacific region, Pfizer Australia, West Ryde, NSW, Australia; 5Medical Affairs, Pfizer Pte Ltd, Singapore Abstract: Poor adherence to statin therapy is linked to significantly increased risk of cardiovascular events and death. Unfortunately, adherence to statins is far from optimal. This is an alarming concern for patients prescribed potentially life-saving cholesterol-lowering medication, especially for those at high risk of cardiovascular events. Research on statin adherence has only recently garnered broader attention; hence, major reasons unique to adherence to statin therapy need to be identified as well as suggestions for countermeasures. An integrated approach to minimizing barriers and enhancing facilitation at the levels of the patient, provider, and health system can help address adherence issues. Health care professionals including physicians, pharmacists, and nurses have an obligation to improve patient adherence, as routine care. In order to achieve sustained results, a multifaceted approach is indispensable. Keywords: cardiovascular disease, nonadherence, nocebo, myopathy, statins

  17. Ketamine: stimulating antidepressant treatment?

    Science.gov (United States)

    Malhi, Gin S; Byrow, Yulisha; Cassidy, Frederick; Cipriani, Andrea; Demyttenaere, Koen; Frye, Mark A; Gitlin, Michael; Kennedy, Sidney H; Ketter, Terence A; Lam, Raymond W; McShane, Rupert; Mitchell, Alex J; Ostacher, Michael J; Rizvi, Sakina J; Thase, Michael E; Tohen, Mauricio

    2016-05-01

    The appeal of ketamine - in promptly ameliorating depressive symptoms even in those with non-response - has led to a dramatic increase in its off-label use. Initial promising results await robust corroboration and key questions remain, particularly concerning its long-term administration. It is, therefore, timely to review the opinions of mood disorder experts worldwide pertaining to ketamine's potential as an option for treating depression and provide a synthesis of perspectives - derived from evidence and clinical experience - and to consider strategies for future investigations. G.S.M. Grant/research support: National Health Medical Research Council, NSW Health, Ramsay Health, American Foundation for Suicide Prevention, AstraZeneca, Eli Lilly & Co, Organon, Pfizer, Servier, and Wyeth; has been a speaker for Abbott, AstraZeneca, Eli Lilly & Co, Janssen Cilag, Lundbeck, Pfizer, Ranbaxy, Servier, and Wyeth; consultant: AstraZeneca, Eli Lilly & Co, Janssen Cilag, Lundbeck, and Servier. M.A.F. Grant support: AssureRx, Janssen Research & Development, Mayo Foundation, Myriad, National Institute of Alcohol Abuse and Alcoholism (NIAAA), National Institute of Mental Health (NIMH), Pfizer. Consultant (Mayo): Janssen Research & Development, LLC, Mitsubishi Tanabe Pharma Corporation, Myriad Genetics, Neuralstem Inc., Sunovion, Supernus Pharmaceuticals, Teva Pharmaceuticals. CME/travel support: American Physician Institute, CME Outfitters. Financial interest/Mayo Clinic 2016: AssureRx. S.H.K. Grant/research support: Brain Canada, Bristol Meyer Squibb, CIHR, Janssen, Johnson & Johnson, Lundbeck, Ontario Brain Institute, Pfizer, Servier, St. Jude Medical, Sunovion. T.A.K. Grant/research support (through Stanford University): Sunovion Pharmaceuticals and Merck & Co., Inc.; consultant/advisory board bember: Allergan, Inc., Janssen Pharmaceuticals, Myriad Genetic Laboratories, Inc., and Sunovion Pharmaceuticals; lecture honoraria (not Speaker's Bureau payments): Glaxo

  18. Etanercept (Enbrel® alternative storage at ambient temperature

    Directory of Open Access Journals (Sweden)

    Shannon E

    2017-07-01

    Full Text Available Edel Shannon,1 Joanne Daffy,2 Heather Jones,3 Andrea Paulson,4 Steven M Vicik5 1Global Chemistry, Manufacturing, and Controls Regulatory, 2Contract Operations Quality Assurance, Pfizer Ireland Pharmaceuticals, Clondalkin, Dublin, Ireland; 3Medical Affairs, Pfizer, Collegeville, PA, USA; 4Pharmaceutical Research and Development, 5Global Supply Product Portfolio Management, Pfizer Biotech, Andover, MA, USA Background: Biologic disease-modifying antirheumatic drugs, including tumor necrosis factor inhibitors such as etanercept (Enbrel®, have improved outcomes for patients with rheumatic and other inflammatory diseases, with sustained remission being the optimal goal for patients with rheumatoid arthritis. Flexible and convenient treatment options, compatible with modern lifestyle, are important in helping patients maintain treatment and manage their disease. Etanercept drug product (DP is available in lyophilized powder (Lyo for solution injection, prefilled syringe, and prefilled pen presentations and is typically stored under refrigerated conditions. We aimed to generate a comprehensive analytical data package from stability testing of key quality attributes, consistent with regulatory requirements, to determine whether the product profile of etanercept is maintained at ambient temperature. Methods: Test methods assessing key attributes of purity, quality, potency, and safety were performed over time, following storage of etanercept DP presentations under a range of conditions. Results: Results and statistical analysis from stability testing (based on size exclusion high-performance liquid chromatography, hydrophobic interaction chromatography, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis Coomassie across all etanercept presentations (10 and 25 mg/vial Lyo DP; 25 and 50 mg prefilled syringe DP; 50 mg prefilled pen DP showed key stability-indicating parameters were within acceptable limits through the alternative storage

  19. Collaborative research between academia and industry using a large clinical trial database: a case study in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Jones Roy

    2011-10-01

    Full Text Available Abstract Background Large clinical trials databases, developed over the course of a comprehensive clinical trial programme, represent an invaluable resource for clinical researchers. Data mining projects sponsored by industry that use these databases, however, are often not viewed favourably in the academic medical community because of concerns that commercial, rather than scientific, goals are the primary purpose of such endeavours. Thus, there are few examples of sustained collaboration between leading academic clinical researchers and industry professionals in a large-scale data mining project. We present here a successful example of this type of collaboration in the field of dementia. Methods The Donepezil Data Repository comprised 18 randomised, controlled trials conducted between 1991 and 2005. The project team at Pfizer determined that the data mining process should be guided by a diverse group of leading Alzheimer's disease clinical researchers called the "Expert Working Group." After development of a list of potential faculty members, invitations were extended and a group of seven members was assembled. The Working Group met regularly with Eisai/Pfizer clinicians and statisticians to discuss the data, identify issues that were currently of interest in the academic and clinical communities that might lend themselves to investigation using these data, and note gaps in understanding or knowledge of Alzheimer's disease that these data could address. Leadership was provided by the Pfizer Clinical Development team leader; Working Group members rotated responsibility for being lead and co-lead for each investigation and resultant publication. Results Six manuscripts, each published in a leading subspecialty journal, resulted from the group's work. Another project resulted in poster presentations at international congresses and two were cancelled due to resource constraints. Conclusions The experience represents a particular approach to

  20. The clinician impact and financial cost to the NHS of litigation over pregabalin: a cohort study in English primary care.

    Science.gov (United States)

    Croker, Richard; Smyth, Darren; Walker, Alex J; Goldacre, Ben

    2018-06-07

    Following litigation over pregabalin's second-use medical patent for neuropathic pain, National Health Service (NHS) England was required by the court to instruct general practitioners (GPs) to prescribe the branded form (Lyrica) for pain. Pfizer's patent was found invalid in 2015, a ruling subject to ongoing appeals. If the Supreme Court appeal in February 2018, whose judgement is awaited, is unsuccessful, the NHS can seek to reclaim excess prescribing costs. We set out to describe the variation in prescribing of pregabalin as branded Lyrica, geographically and over time; to determine how clinicians responded to the NHS England instruction to GPs; and to model excess costs to the NHS attributable to the legal judgements. English primary care. English general practices. Variation in prescribing of branded Lyrica across the country before and after the NHS England instruction, by practice and by Clinical Commissioning Group; excess prescribing costs. The proportion of pregabalin prescribed as Lyrica increased from 0.3% over 6 months before the NHS England instruction (September 2014 to February 2015) to 25.7% afterwards (April to September 2015). Although 70% of pregabalin is estimated to be for pain, including neuropathic pain, only 11.6% of practices prescribed Lyrica at this level; the median proportion prescribed as Lyrica was 8.8% (IQR 1.1%-41.9%). If pregabalin had come entirely off patent in September 2015, and Pfizer had not appealed, we estimate the NHS would have spent £502 million less on pregabalin to July 2017. NHS England instructions to GPs regarding branded prescription of pregabalin were widely ignored and have created much debate around clinical independence in prescribing. Protecting revenue from 'skinny labels' will pose a challenge. If Pfizer's final appeal on the patent is unsuccessful, the NHS can seek reimbursement of excess pregabalin prescribing costs, potentially £502 million. © Article author(s) (or their employer(s) unless

  1. An economic model to compare linezolid and vancomycin for the treatment of confirmed methicillin-resistant Staphylococcus aureus nosocomial pneumonia in Germany

    Directory of Open Access Journals (Sweden)

    Patel DA

    2014-10-01

    Full Text Available Dipen A Patel,1 Andre Michel,2 Jennifer Stephens,1 Bertram Weber,3 Christian Petrik,4 Claudie Charbonneau5 1Health Economic and Outcomes Research, Pharmerit International, Bethesda, MD, USA; 2Klinikum Hanau GmbH, Hanau, Germany; 3Health Technology Assessment and Outcomes Research, 4Anti-infectives, Pfizer, Berlin, Germany; 5Pfizer International Operations, Pfizer France, Paris, France Background: Across Europe, methicillin-resistant Staphylococcus aureus (MRSA is considered to be the primary cause of nosocomial pneumonia (NP. In Germany alone, approximately 14,000 cases of MRSA-associated NP occur annually, which may have a significant impact on health care resource use and associated economic costs. The objective of this study was to investigate the economic impact of linezolid compared with that of vancomycin in the treatment of hospitalized patients with MRSA-confirmed NP in the German health care system. Methods: A 4-week decision tree model incorporated published data and expert opinion on clinical parameters, resource use, and costs (2012 euros was constructed. The base case first-line treatment duration for patients with MRSA-confirmed NP was 10 days. Treatment success (survival, failure due to lack of efficacy, serious adverse events, and mortality were possible outcomes that could impact costs. Alternate scenarios were analyzed, such as varying treatment duration (7 or 14 days or treatment switch due to a serious adverse event/treatment failure (at day 5 or 10. Results: The model calculated total base case inpatient costs of €15,116 for linezolid and €15,239 for vancomycin. The incremental cost-effectiveness ratio favored linezolid (versus vancomycin, with marginally lower costs (by €123 and greater efficacy (+2.7% absolute difference in the proportion of patients successfully treated for MRSA NP. Approximately 85%–87% of the total treatment costs were attributed to hospital stay (primarily in the intensive care unit

  2. Burden of vasomotor symptoms in France, Germany, Italy, Spain, and the United Kingdom

    Directory of Open Access Journals (Sweden)

    DiBonaventura MD

    2013-05-01

    Full Text Available Marco daCosta DiBonaventura,1 Arthi Chandran,2 Ming-Ann Hsu,3 Andrew Bushmakin41Health Outcomes Practice, Kantar Health, New York, NY, USA; 2Global Health Economics and Outcomes Research, Pfizer, Inc., New York, NY, USA; 3Global Health Economics and Outcomes Research, Pfizer, Inc., Groton, CT, USA; 4Global Research and Development, Pfizer, Inc., Groton, CT, USABackground: Several studies have documented a significant association between vasomotor symptoms (VMS and a decrement in health outcomes among postmenopausal women, but these studies have mostly focused on the US. The aim of the current study was to broaden this investigation by examining the burden of VMS symptoms in the European Union with respect to both humanistic and economic outcomes.Methods: All women aged 40–75 years who completed the 2010 5EU (France, Germany, Italy, Spain, and the UK National Health and Wellness Survey were identified as potential respondents and invited to participate in an additional cross-sectional, Internet-based survey. Only postmenopausal women from 5EU were included in the current analyses (n = 3801. VMS was assessed using the Menopausal Rating Scale, and was used in multiple regression models as the primary predictor of health status (EQ-5D-3L, work productivity loss, and the number of physician visits due to menopause.Results: Over half (50.3% of postmenopausal women experienced either mild (24.6%, moderate (17.6%, or severe (8.1% VMS. Controlling for confounding variables, mild (b = −0.03, P < 0.05, moderate (b = −0.07, P < 0.05, and severe VMS (b = −0.17, P < 0.05 were each associated with worse health utilities relative to women without VMS. Similarly, increased resource use (b = 1.04–2.39, all P < 0.05, overall work impairment (b = 8.71–19.69, all P < 0.05, and activity impairment (b = 11.22–24.54, all P < 0.05 were also observed as VMS severity increased (with each b representing the difference between each level of severity and the

  3. Double-blind comparison of ziprasidone and risperidone in the treatment of Chinese patients with acute exacerbation of schizophrenia

    Directory of Open Access Journals (Sweden)

    Hongyan Zhang

    2011-03-01

    Full Text Available Hongyan Zhang1, Huafang Li2, Liang Shu1, Niufan Gu2, Gang Wang3, Yongzhen Weng3, Shiping Xie4, Xinbao Zhang4, Ting Li5, Cui Ma5, Wei Yu6, Bruce Parsons7, Manjula Schou81Institute of Mental Health, Peking University, Beijing, China; 2Shanghai Mental Health Center, Shanghai, China; 3Capital Medical University, Beijing An Ding Hospital, Beijing, China; 4Nanjing Brain Hospital, Nanjing, China; 5Guangzhou Brain Hospital, Guangzhou, China; 6Pfizer China, Beijing, China; 7Pfizer Inc, New York, NY, USA; 8Pfizer Australia, Sydney, AustraliaBackground: The aim of the study was to evaluate the efficacy and safety of ziprasidone versus risperidone in Chinese subjects with acute exacerbation of schizophrenia.Methods: In patients meeting the Chinese Classification of Mental Disorders criteria for schizophrenia and with a Positive and Negative Syndrome Scale (PANSS total score ≥60 were randomly assigned to six weeks of double-blind treatment with ziprasidone 40–80 mg twice daily or risperidone 1–3 mg bid, flexibly dosed. Noninferiority was demonstrated if the upper limit of the two-sided 95% confidence interval (CI for the difference in PANSS total score improvement from baseline in the evaluable population was smaller than the prespecified noninferiority margin of 10 units.Results: The intent-to-treat population comprised 118 ziprasidone-treated and 121 risperidone-treated subjects. Improvement (reduction from baseline to week 6 in PANSS total score was (-35.6 [95% CI: -38.6, -32.6] for ziprasidone and (-37.1 [95% CI: -39.9, -34.4] for risperidone. Noninferiority was demonstrated in the evaluable population with a difference score of 1.5 [95% CI: -2.5, 5.5]. Mean prolactin levels decreased at week 6 compared with baseline for ziprasidone (-3.5 ng/mL, but significantly increased for risperidone (61.1 ng/mL; P < 0.001. More risperidone-treated subjects (14.9% than ziprasidone-treated subjects (4.2% reported weight gain ≥7%. Akathisia and somnolence in

  4. Amikacin Dosing and Monitoring in Spinal Cord Injury Patients: Variation in Clinical Practice Between Spinal Injury Units and Differences in Experts' Recommendations

    Directory of Open Access Journals (Sweden)

    Subramanian Vaidyanathan

    2006-01-01

    Full Text Available The objective of this article was to determine the current practice on amikacin dosing and monitoring in spinal cord injury patients from spinal cord physicians and experts. Physicians from spinal units and clinical pharmacologists were asked to provide protocol for dosing and monitoring of amikacin therapy in spinal cord injury patients. In a spinal unit in Poland, amikacin is administered usually 0.5 g twice daily. A once-daily regimen of amikacin is never used and amikacin concentrations are not determined. In Belgium, Southport (U.K., Spain, and the VA McGuire Medical Center (Richmond, Virginia, amikacin is given once daily. Whereas peak and trough concentrations are determined in Belgium, only trough concentration is measured in Southport. In both these spinal units, modification of the dose is not routinely done with a nomogram. In Spain and the VA McGuire Medical Center, monitoring of serum amikacin concentration is not done unless a patient has renal impairment. In contrast, the dose/interval of amikacin is adjusted according to pharmacokinetic parameters at the Edward Hines VA Hospital (Hines, Illinois, where amikacin is administered q24h or q48h, depending on creatinine clearance. Spinal cord physicians from Denmark, Germany, and the Kessler Institute for Rehabilitation (West Orange, New Jersey state that they do not use amikacin in spinal injury patients. An expert from Canada does not recommend determining serum concentrations of amikacin, but emphasizes the value of monitoring ototoxicity and nephrotoxicity. Experts from New Zealand recommend amikacin in conventional twice- or thrice-daily dosing because of the theoretical increased risk of neuromuscular blockade and apnea with larger daily doses in spinal cord injury patients. On the contrary, experts from Greece, Israel, and the U.S. recommend once-daily dosing and determining amikacin pharmacokinetic parameters for each patient. As there is considerable variation in clinical

  5. Evaluation of a second uterine flushing on embryo recovery in Nelore cows / Avaliação de uma segunda lavagem uterina sobre a recuperacão de embriões em vacas Nelore

    Directory of Open Access Journals (Sweden)

    Marcelo Marcondes Seneda

    2008-08-01

    Full Text Available The objective of the present study was to evaluate the effect of a second uterine flushing on number of recovered embryos. Cyclic Nelore cows (n= were used as donors. Animals were kept under grazing conditions in a farm at Mamborê, Paraná state. Cows were submitted to two sessions of multiple ovulation 80 days apart. At a random stage of estrus cycle (Day 0 donors received an intravaginal device with 1.9 g of progesterone (CIDR; Pfizer; Brasil. Twenty four hours later (Day 1 cows were injected with 2.5 mg/ IM of Estradiol Benzoate (Estrogin, Farmavet, Brasil. Between Day 5 and Day 9, donors received decreasing doses of 250 UI of FSH (Pluset; Calier, Brasil. On Days 7 and cows received 25 mg/ IM of dinoprost (Lutalyse, Pfizer, Brasil and progesterone implants were removed 12 hs later. Artificial insemination was performed 12 and 24 hours after estrus detection. The first embryo recovery was performed 7 days after AI with the Foley catheter positioned in the uterine body. A total of 1.000 mL of PBS (Embriocare, Cultilab, Brasil was used in a closed system of uterine flushing, with a 70 µm filter. Recovered uterine fluid was evaluated under a stereomicroscope (SMZ 654, Nikon, Japan and embryos were classified accord to IETS (1998. Twenty four hours later, the second uterine flushing was performed following the same procedure. Results were analyzed by t-Student test (p O objetivo do presente experimento foi verificar a viabilidade de uma segunda lavagem uterina sobre a recuperação de embriões. Doadoras cíclicas da raça Nelore (n= foram mantidas a pasto no município de Mamborê, Estado do Paraná. Os animais foram submetidos a tratamentos de superovulação com intervalo de 80 dias. Em um dia aleatório do ciclo estral (Dia 0 as doadoras receberam um dispositivo intravaginal contendo 1,9 g de progesterona (CIDR; Pfizer, Brasil. Vinte e quatro horas após (Dia 1 administrou-se , mg de benzoato de Estradiol (Estrogin; Farmavet, Brasil por via

  6. Drawing theories apart the dispersion of Feynman diagrams in postwar physics

    CERN Document Server

    Kaiser, David

    2005-01-01

    Winner of the 2007 Pfizer Prize from the History of Science Society. Feynman diagrams have revolutionized nearly every aspect of theoretical physics since the middle of the twentieth century. Introduced by the American physicist Richard Feynman (1918-88) soon after World War II as a means of simplifying lengthy calculations in quantum electrodynamics, they soon gained adherents in many branches of the discipline. Yet as new physicists adopted the tiny line drawings, they also adapted the diagrams and introduced their own interpretations. Drawing Theories Apart traces how generations of young theorists learned to frame their research in terms of the diagrams—and how both the diagrams and their users were molded in the process.Drawing on rich archival materials, interviews, and more than five hundred scientific articles from the period, Drawing Theories Apart uses the Feynman diagrams as a means to explore the development of American postwar physics. By focusing on the ways young physicists learned new calcul...

  7. Carbon steel protection in G.S. (Girlder sulfide) plants. CITROSOLV process influence. Pt. 6

    International Nuclear Information System (INIS)

    Lires, O.A.; Burkart, A.L.; Delfino, C.A.; Rojo, E.A.

    1988-01-01

    In order to protect carbon steel towers and piping of Girlder sulfide (G.S.) experimental heavy water plants against corrosion produced by the action of aqueous solutions of hydrogen sulfides, a method, previously published, was developed. Carbon steel, exposed to saturated aqueous solutions of hydrogen sulfide, forms iron sulfide scales. In oxygen free solutions evolution of corrosion follows the sequence: mackinawite → cubic ferrous sulfide → troilite → pyrrotite → pyrite. Scales formed by pyrrotite-pyrite or pyrite are the most protective layers (these are obtained at 130 deg C, 2 MPa, for periods of 14 days). CITROSOLV Process (Pfizer) is used to descaling and passivating stainless steel plant's components. This process must be used in mixed (carbon steel - stainless steel) circuits and may cause the formation of magnetite scales over the carbon steel. The influence of magnetite in the pyrrotite-pyrite scales formation is studied in this work. (Author) [es

  8. Is exercise important in chronic obstructive pulmonary disease?

    Science.gov (United States)

    Make, Barry; Casaburi, Richard

    2007-09-01

    Chronic obstructive pulmonary disease impairs the ability of patients to perform maximal physical exercise, particularly in patients with severe lung disease. However, differing perceptions of the meaning and importance of exercise to patients and caregivers is likely to impair patient-physician communication about current medical status and outcomes of therapeutic interventions. Other outcomes of importance to patients including actual performance of functional activity during daily life and health-related quality of life may also be affected by impaired exercise capacity. However, the relationships between exercise, activity, and quality of life are inconsistent. Thus, measurement of physiologic and patient-centered outcomes may provide the best approach to assessing responses to therapeutic interventions. These concepts were explored in a conference sponsored by Boehringer Ingelheim Pharmaceuticals, Inc. and Pfizer Inc and reviewed in the articles generated from the symposium in this issue of COPD.

  9. Probability of major depression diagnostic classification using semi-structured versus fully structured diagnostic interviews.

    Science.gov (United States)

    Levis, Brooke; Benedetti, Andrea; Riehm, Kira E; Saadat, Nazanin; Levis, Alexander W; Azar, Marleine; Rice, Danielle B; Chiovitti, Matthew J; Sanchez, Tatiana A; Cuijpers, Pim; Gilbody, Simon; Ioannidis, John P A; Kloda, Lorie A; McMillan, Dean; Patten, Scott B; Shrier, Ian; Steele, Russell J; Ziegelstein, Roy C; Akena, Dickens H; Arroll, Bruce; Ayalon, Liat; Baradaran, Hamid R; Baron, Murray; Beraldi, Anna; Bombardier, Charles H; Butterworth, Peter; Carter, Gregory; Chagas, Marcos H; Chan, Juliana C N; Cholera, Rushina; Chowdhary, Neerja; Clover, Kerrie; Conwell, Yeates; de Man-van Ginkel, Janneke M; Delgadillo, Jaime; Fann, Jesse R; Fischer, Felix H; Fischler, Benjamin; Fung, Daniel; Gelaye, Bizu; Goodyear-Smith, Felicity; Greeno, Catherine G; Hall, Brian J; Hambridge, John; Harrison, Patricia A; Hegerl, Ulrich; Hides, Leanne; Hobfoll, Stevan E; Hudson, Marie; Hyphantis, Thomas; Inagaki, Masatoshi; Ismail, Khalida; Jetté, Nathalie; Khamseh, Mohammad E; Kiely, Kim M; Lamers, Femke; Liu, Shen-Ing; Lotrakul, Manote; Loureiro, Sonia R; Löwe, Bernd; Marsh, Laura; McGuire, Anthony; Mohd Sidik, Sherina; Munhoz, Tiago N; Muramatsu, Kumiko; Osório, Flávia L; Patel, Vikram; Pence, Brian W; Persoons, Philippe; Picardi, Angelo; Rooney, Alasdair G; Santos, Iná S; Shaaban, Juwita; Sidebottom, Abbey; Simning, Adam; Stafford, Lesley; Sung, Sharon; Tan, Pei Lin Lynnette; Turner, Alyna; van der Feltz-Cornelis, Christina M; van Weert, Henk C; Vöhringer, Paul A; White, Jennifer; Whooley, Mary A; Winkley, Kirsty; Yamada, Mitsuhiko; Zhang, Yuying; Thombs, Brett D

    2018-06-01

    Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.AimsTo evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics. Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit. A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15-3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98-10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7-15) (OR = 0.96; 95% CI = 0.56-1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26-0.97). The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.Declaration of interestDrs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the

  10. Patents, antibiotics, and autarky in Spain.

    Science.gov (United States)

    Romero De Pablos, Ana

    2014-01-01

    Patents on antibiotics were introduced in Spain in 1949. Preliminary research reveals diversification in the types of antibiotics: patents relating to penicillin were followed by those relating to streptomycin, erythromycin and tetracycline. There was also diversification in the firms that applied for patents: while Merck & Co. Incorporated and Schenley Industries Inc. were the main partners with Spanish antibiotics manufacturers in the late 1940s, this industrial space also included many others, such as Eli Lilly & Company, Abbott Laboratories, Chas. Pfizer & Co. Incorporated, and American Cyanamid Company in the mid-1970s. The introduction of these drugs in Spain adds new elements to a re-evaluation of the autarkic politics of the early years of the Franco dictatorship.

  11. Neratinib: First Global Approval.

    Science.gov (United States)

    Deeks, Emma D

    2017-10-01

    Neratinib (Nerlynx™) is an oral, irreversible inhibitor of the human epidermal growth factor receptors HER1 (EGFR), HER2 and HER4. The drug originally arose from research by Wyeth (now Pfizer) and is now being developed by Puma Biotechnology primarily for the treatment of HER2-positive (HER+) breast cancer. Neratinib is approved in the USA for the extended adjuvant treatment of patients with HER2+ early-stage breast cancer who have been previously treated with a trastuzumab-based adjuvant regimen, and is in the preregistration phase for this indication in the EU. Neratinib, as monotherapy and/or combination therapy, is also in phase 3 development for metastatic breast cancer and in phase 1/2 development for advanced breast cancer and other solid tumours, including non-small cell lung cancer, colorectal cancer and glioblastoma. This article summarizes the milestones in the development of neratinib leading to this first approval for breast cancer.

  12. National Working Group Meeting on ALK diagnostics in lung cancer.

    Science.gov (United States)

    Cooper, Wendy; Fox, Stephen; O'Toole, Sandra; Morey, Adrienne; Frances, Glenn; Pavlakis, Nick; O'Byrne, Kenneth; Dettrick, Andrew; Leong, Trishe; Rathi, Vivek; Spagnolo, Dominic; Hemmings, Chris; Singh, Mahendra; Moffat, David; Tsao, Ming-Sound; Wilner, Keith; Buller, Richard; Pitman Lowenthal, Susan; Arifeen, Shams; Binko, Justin; Alam, Mahmood

    2014-04-01

    The global landscape of molecular testing is rapidly changing, with the recent publication of the International Association for the Study of Lung Cancer (IASLC)/College of American Pathologists (CAP) guidelines and the ALK Atlas. The IASLC/CAP guidelines recommend that tumors from patients with non-small cell lung cancer (NSCLC) be tested for ALK rearrangements in addition to epidermal growth factor receptor (EGFR) mutations. The spur for this recommendation is the availability of novel therapies that target these rearrangements. This article is based on coverage of a Pfizer-sponsored National Working Group Meeting on ALK Diagnostics in Lung Cancer, held around the 15th World Lung Cancer Conference, in Sydney on October 31, 2013. It is based on the presentations given by the authors at the meeting and the discussion that ensued. The content for this article was discussed and agreed on by the authors. © 2014 Wiley Publishing Asia Pty Ltd.

  13. Chemical gel barriers as low-cost alternative to containment and in situ cleanup of hazardous wastes to protect groundwater

    International Nuclear Information System (INIS)

    1997-01-01

    Chemical gel barriers are being considered as a low-cost alternative for containment and in situ cleanup of hazardous wastes to protect groundwater. Most of the available gels in petroleum application are non-reactive and relative impermeable, providing a physical barriers for all fluids and contaminants. However, other potential systems can be envisioned. These systems could include gels that are chemically reactive and impermeable such that most phase are captured by the barriers but the contaminants could diffuse through the barriers. Another system that is chemically reactive and permeable could have potential applications in selectivity capturing contaminants while allowing water to pass through the barriers. This study focused on chemically reactive and permeable gel barriers. The gels used in experiment are DuPont LUDOX SM colloidal silica gel and Pfizer FLOPAAM 1330S hydrolyzed polyacrylamide (HPAM) gel

  14. Using search engine query data to track pharmaceutical utilization: a study of statins.

    Science.gov (United States)

    Schuster, Nathaniel M; Rogers, Mary A M; McMahon, Laurence F

    2010-08-01

    To examine temporal and geographic associations between Google queries for health information and healthcare utilization benchmarks. Retrospective longitudinal study. Using Google Trends and Google Insights for Search data, the search terms Lipitor (atorvastatin calcium; Pfizer, Ann Arbor, MI) and simvastatin were evaluated for change over time and for association with Lipitor revenues. The relationship between query data and community-based resource use per Medicare beneficiary was assessed for 35 US metropolitan areas. Google queries for Lipitor significantly decreased from January 2004 through June 2009 and queries for simvastatin significantly increased (P patent (P global revenues from 2004 to 2008 (P search engine queries for medical information correlate with pharmaceutical revenue and with overall healthcare utilization in a community. This suggests that search query data can track community-wide characteristics in healthcare utilization and have the potential for informing payers and policy makers regarding trends in utilization.

  15. Avelumab: First Global Approval.

    Science.gov (United States)

    Kim, Esther S

    2017-05-01

    Avelumab (Bavencio ® ) is an intravenously administered programmed cell death ligand-1-blocking human antibody initially developed by EMD Serono Inc. (the biopharmaceutical division of Merck KGaA, Darmstadt, Germany) [now jointly developed and commercialized by EMD Serono Inc. and Pfizer] for the treatment of various tumours. It has received accelerated approval in the USA for the treatment of metastatic Merkel cell carcinoma (mMCC) in adults and paediatric patients aged ≥12 years. The marketing authorization application for avelumab in the treatment of mMCC is undergoing regulatory review in the EU, the biologics license application for avelumab in the treatment of urothelial carcinoma is undergoing priority review by the FDA, and avelumab is in various stages of development internationally for a variety of cancers. This article summarizes the milestones in the development of avelumab leading to this first approval for mMCC.

  16. Effect of sildenafil on gastric emptying and postprandial frequency of antral contractions in healthy humans

    DEFF Research Database (Denmark)

    Madsen, J L; Søndergaard, S B; Fuglsang, S

    2004-01-01

    BACKGROUND: Sildenafil is known to block phosphodiesterase type 5, which degrades nitric oxide-stimulated cyclic guanosine monophosphate, thereby relaxing smooth muscle cells in various organs. The effect of sildenafil on gastric motor function after a meal was investigated in healthy humans....... METHODS: Ten healthy male volunteers (21-28 years) participated in a placebo-controlled, double-blind, cross-over study. In random order and on two separate days each volunteer ingested either 50 mg sildenafil (Viagra, Pfizer, New York, N.Y., USA) or placebo. A gamma camera technique was used to measure......: A single dose of 50 mg sildenafil does not change gastric emptying or postprandial frequency of antral contractions in healthy volunteers....

  17. Very unsuccessful attempts to quit: examining correlates in the 13 countries where almost 2/3 of smokers live

    Directory of Open Access Journals (Sweden)

    João Mauricio Castaldelli-Maia

    2017-05-01

    The Global Adult Tobacco Survey (GATS functions as a multi-partner initiative that represents global, regional, and national organizations. We acknowledge WHO, CDC, GATS Implementing Agency, Johns Hopkins Bloomberg School of Public Health, RTI International, and the National Governments of Bangladesh, Brazil, China, Egypt, India, Indonesia, Mexico, Philippines, Russia, Thailand, Turkey, Ukraine, and Vietnam, for carrying out such an important survey, and releasing data for public use. Dr. Castaldelli-Maia receives a Pfizer Independent Grant for Learning and Change (IGLC managed by Global Bridges (Healthcare Alliance for Tobacco Dependence Treatment hosted at the Mayo Clinic, to support free smoking cessation treatment training in addiction/mental health care units in Brazil (grant IGLC 13513957. The above had no connection to the present study.

  18. COPD exacerbations associated with the modified Medical Research Council scale and COPD assessment test among Humana Medicare members

    Directory of Open Access Journals (Sweden)

    Pasquale MK

    2016-01-01

    Full Text Available Margaret K Pasquale,1 Yihua Xu,1 Christine L Baker,2 Kelly H Zou,3 John G Teeter,4 Andrew M Renda,5 Cralen C Davis,1 Theodore C Lee,6 Joel Bobula2 1Comprehensive Health Insights, Inc., Humana Inc., Louisville, KY, 2Outcomes and Evidence, Global Health & Value, Pfizer Inc., 3Statistical Center for Outcomes, Real-World and Aggregate Data, Global Innovative Pharma Business, Pfizer Inc., New York, NY, 4Global Medical Development, Global Innovative Pharma Business, Pfizer Inc., Groton, CT, 5Retail Strategy & Execution, Humana Inc., Louisville, KY, 6Global Medical Affairs, Global Innovative Pharma Business, Pfizer Inc., New York, NY, USA Background: The Global initiative for chronic Obstructive Lung Disease guidelines recommend assessment of COPD severity, which includes symptomatology using the modified Medical Research Council (mMRC or COPD assessment test (CAT score in addition to the degree of airflow obstruction and exacerbation history. While there is great interest in incorporating symptomatology, little is known about how patient reported symptoms are associated with future exacerbations and exacerbation-related costs.Methods: The mMRC and CAT were mailed to a randomly selected sample of 4,000 Medicare members aged >40 years, diagnosed with COPD (≥2 encounters with International Classification of Dis­eases-9th Edition Clinical Modification: 491.xx, 492.xx, 496.xx, ≥30 days apart. The exacerbations and exacerbation-related costs were collected from claims data during 365-day post-survey after exclusion of members lost to follow-up or with cancer, organ transplant, or pregnancy. A logistic regression model estimated the predictive value of exacerbation history and symptomatology on exacerbations during follow-up, and a generalized linear model with log link and gamma distribution estimated the predictive value of exacerbation history and symptomatology on exacerbation-related costs.Results: Among a total of 1,159 members who returned the

  19. Effect of Apixaban Versus Warfarin Use on Health Care Resource Utilization and Costs Among Elderly Patients with Nonvalvular Atrial Fibrillation.

    Science.gov (United States)

    Deitelzweig, Steven; Luo, Xuemei; Gupta, Kiran; Trocio, Jeffrey; Mardekian, Jack; Curtice, Tammy; Lingohr-Smith, Melissa; Menges, Brandy; Lin, Jay

    2017-11-01

    associated with less HCRU and lower total all-cause health care costs and costs for bleeding- and stroke-related medical services, but greater pharmacy costs, among elderly NVAF patients. This study was sponsored by Pfizer and Bristol-Myers Squibb. Deitelzweig is a consultant for Pfizer and Bristol-Myers Squibb and has served on their advisory boards and received speaker fees. Deitelzweig also serves as consultant and advisory board member to Portola and Janssen. Luo, Trocio, and Mardekian are employees of Pfizer and own stock in the company. Gupta and Curtice are employees of Bristol-Myers Squibb and own stock in the company. Lingohr-Smith, Menges, and Lin are employees of Novosys Health, which received research funds from Pfizer and Bristol-Myers Squibb to conduct this study and develop the manuscript. Study concept and design were primarily contributed by Deitelzweig, Luo, and Gupta, along with Trocio, Mardekian, Curtice, and Lin. Lin, Menges, and Lingohr-Smith took the lead in data collection, with assistance from the other authors. Data interpretation was performed by Deitelzweig, Menges, and Lin, with assistance from the other authors. The manuscript was written by Lingohr-Smith and Menges, along with the other authors, and revised by all the authors. Some aspects of this study were presented at the American Heart Association Scientific Sessions in New Orleans, Louisiana, November 12-16, 2016.

  20. High levels of confusion for cholesterol awareness campaigns.

    Science.gov (United States)

    Hall, Danika V

    2008-09-15

    Earlier this year, two industry-sponsored advertising campaigns for cholesterol awareness that target the general public were launched in Australia. These campaigns aimed to alert the public to the risks associated with having high cholesterol and encouraged cholesterol testing for wider groups than those specified by the National Heart Foundation. General practitioners should be aware of the potential for the two campaigns to confuse the general public as to who should be tested, and where. The campaign sponsors (Unilever Australasia and Pfizer) each have the potential to benefit by increased market share for their products, and increased profits. These disease awareness campaigns are examples of what is increasingly being termed "condition branding" by pharmaceutical marketing experts.

  1. "Center punch" and "whole spot" bioanalysis of apixaban in human dried blood spot samples by UHPLC-MS/MS.

    Science.gov (United States)

    Zheng, Naiyu; Yuan, Long; Ji, Qin C; Mangus, Heidi; Song, Yan; Frost, Charles; Zeng, Jianing; Aubry, Anne-Françoise; Arnold, Mark E

    2015-04-15

    Apixaban (Eliquis™) was developed by Bristol-Myers Squibb (BMS) and Pfizer to use as an antithrombotic/anticoagulant agent and has been recently approved for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. A clinical study of apixaban, sponsored by BMS and Pfizer, included a pilot exploratory portion to evaluate the potential for future drug concentration monitoring using dried blood spot (DBS) sample collection. For DBS sample collection, a fixed blood volume was dispensed onto a DBS card by either regular volumetric pipette (venous blood collection) or capillary dispenser (finger prick blood collection). A 96-well semi-automated liquid-liquid extraction sample preparation procedure was developed to provide clean extracts for UHPLC-MS/MS quantitation. Assays using both partial-spot center punch and whole spot punch were developed and validated. The linear dynamic ranges for all the analyses were from 0.5 to 500 ng/mL. The coefficient of determination (r(2)) values was >0.9944 for all the validation runs. For the center punch approach, the intra-assay precision (%CV) was within 4.4% and inter-assay precision was within 2.6%. The assay accuracy, expressed as %Dev., was within ± 5.4% of the nominal concentrations. One accuracy and precision run was performed using the whole spot approach, the intra-assay precision (%CV) was within 7.1% and the accuracy was within ± 8.0% of the nominal concentrations. In contrast to the center punch approach, the whole spot approach eliminated the effect of hematocrit and high lipids on the analysis of apixaban in human DBS when an accurate sample blood volume was collected on DBS cards. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Results from an international multicenter trial evaluating the ease-of-use of and preference for a newly developed disposable injection pen for the treatment of growth hormone deficiency in treatment-naïve children and adults

    Science.gov (United States)

    Pleil, Andreas M; Darendeliler, Feyza; Dörr, Helmuth G; Hutchinson, Katherine; Wollmann, Hartmut A

    2014-01-01

    Previous research has reported that ease of use of and preference for a delivery device are associated with greater patient compliance – an important factor in achieving optimal therapeutic results. The objective of this study was to assess the ease-of-use of a new disposable pen (GoQuick®, Pfizer, Inc.) versus the current reusable pen (GENOTROPIN Pen®, Pfizer, Inc.) to inject a daily dose of recombinant DNA origin human growth hormone, Genotropin® (somatropin) in standard practice. In this randomized, crossover, multicenter, multinational, open-label study, ease-of-use of and preference for the two pens were assessed in three treatment-naïve populations: 1) parents of very young children; 2) parent–child dyads; and 3) adults via use of a validated self-report Injection Pen Assessment Questionnaire (IPAQ) after 2 months of at-home-use experience. The primary endpoint was the proportion of participants who reported the new disposable pen to be no different from or easier to use than the current reusable pen. Safety was also assessed and reported according to local legal requirements. Of the 120 screened patients, 119 were included in the ease-of-use analysis and all were included in the safety analyses. In all, 67.2% found the new somatropin disposable pen to be no different from or easier to use than the reusable pen (95% confidence interval: 58.8–75.7). Most adverse events were mild or moderate. No deaths or device- or treatment-related serious adverse events were reported. These results suggest that improvements made to the reusable somatropin pen are tangible and recognizable to treatment-naïve patients and their caregivers, child–caregiver dyads, and adults, and may positively impact continued compliance with therapy. Registry information ClinicalTrials.gov identifier: NCT01112865. PMID:24748824

  3. [Vaccine does make sense, until used].

    Science.gov (United States)

    Kobayashi, Toshi-Hiko

    2011-01-01

    In the 1990s, drug companies focused their resources on chemistry-based proprietary blockbuster compounds (small molecules) for chronic diseases that could bring in several billion dollars in a short period of time. Since then, the focus has turned to biologics (proteins/high MW molecules) such as anticancer agents, antibodies, and so on. Vaccines, in contrast, are a rather slow-growing market, administered only a few times per patient, low priced, and often undifferentiated. Due to the influenza scares of recent years, the above view has changed remarkably. According to some analysts, the annual growth of the current $2.2 bn vaccine market will become almost 10 percent over the next 5 years. In 2009, Pfizer (US), in an effort to boost their small vaccine-related business, purchased Wyeth (US). In October 2010, Johnson & Johnson announced they were buying Crucell (Germany), the only vaccine maker who had remained independent. GSK (UK) holds the top spot in the vaccine market with a 25% share. Pfizer (US), Merck (US), Novartis (Switzerland), and Sanofi-Aventis (France) are next, while Johnson & Johnson has moved into the 6th position by purchasing Crucell. There is of course an essential therapeutic need for vaccines, however, why are major pharmaceutical companies now investing a significant amount of resources in the vaccine business? Vaccine development may take more time than that of small molecules, but they are less risky from an intellectual property standpoint, and complicated manufacturing processes create a high barrier to follow-on biologics/biosimilars. Also in Japan, since the recent influenza scares, there has been acceleration in movement and cooperation among industry and government, including lawmakers.

  4. Narrative review: the promotion of gabapentin: an analysis of internal industry documents.

    Science.gov (United States)

    Steinman, Michael A; Bero, Lisa A; Chren, Mary-Margaret; Landefeld, C Seth

    2006-08-15

    Internal documents from the pharmaceutical industry provide a unique window for understanding the structure and methods of pharmaceutical promotion. Such documents have become available through litigation concerning the promotion of gabapentin (Neurontin, Pfizer, Inc., New York, New York) for off-label uses. To describe how gabapentin was promoted, focusing on the use of medical education, research, and publication. Court documents available to the public from United States ex. rel David Franklin vs. Pfizer, Inc., and Parke-Davis, Division of Warner-Lambert Company, mostly from 1994-1998. All documents were reviewed by 1 author, with selected review by coauthors. Marketing strategies and tactics were identified by using an iterative process of review, discussion, and re-review of selected documents. The promotion of gabapentin was a comprehensive and multifaceted process. Advisory boards, consultants meetings, and accredited continuing medical education events organized by third-party vendors were used to deliver promotional messages. These tactics were augmented by the recruitment of local champions and engagement of thought leaders, who could be used to communicate favorable messages about gabapentin to their physician colleagues. Research and scholarship were also used for marketing by encouraging "key customers" to participate in research, using a large study to advance promotional themes and build market share, paying medical communication companies to develop and publish articles about gabapentin for the medical literature, and planning to suppress unfavorable study results. Most available documents were submitted by the plaintiff and may not represent a complete picture of marketing practices. Activities traditionally considered independent of promotional intent, including continuing medical education and research, were extensively used to promote gabapentin. New strategies are needed to ensure a clear separation between scientific and commercial activity.

  5. High heterogeneity and low reliability in the diagnosis of major depression will impair the development of new drugs.

    Science.gov (United States)

    Lieblich, Samuel M; Castle, David J; Pantelis, Christos; Hopwood, Malcolm; Young, Allan Hunter; Everall, Ian P

    2015-10-01

    Major depressive disorder is a common diagnosis associated with a high burden of disease that has proven to be highly heterogeneous and unreliable. Treatments currently available demonstrate limited efficacy and effectiveness. New drug development is urgently required but is likely to be hindered by diagnostic limitations. D.J.C. has received grants and personal fees from Eli Lilly, Janssen-Cilag, Roche, Allergen, Bristol-Myers Squibb, Pfizer, Lundbeck, AstraZeneca, Hospira, Organon, Sanofi-Aventis, and Wyeth during the writing of this review. C.P. has received grant support from Janssen-Cilag, Eli Lilly, Hospira (Mayne), AstraZeneca, and received honoraria for consultancy to Janssen-Cilag, Eli Lilly, Hospira (Mayne), AstraZeneca, Pfizer, Schering Plough, and Lundbeck. Over the past 2 years he has participated on advisory boards for Janssen-Cilag and Lundbeck, and received honoraria for talks presented at educational meetings organised by AstraZeneca, Janssen-Cilag and Lundbeck. M.H. has received personal fees or grants from Lundbeck, AstraZeneca and Servier during the writing of this review. A.H.Y. reports personal fees from Lundbeck, Sunovion, AstraZeneca and Janssen outside the submitted work. I.P.E. has received personal fees or grants from Lundbeck, AstraZeneca, and Abbvie during the writing of this review. © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

  6. Internet-ordered viagra (sildenafil citrate) is rarely genuine.

    Science.gov (United States)

    Campbell, Neil; Clark, John P; Stecher, Vera J; Goldstein, Irwin

    2012-11-01

    Counterfeit medication is a growing problem. This study assessed the requirement for prescription, cost, origin, and content of medications sold via the Internet and purporting to be the phosphodiesterase type 5 inhibitor Viagra (sildenafil citrate). Pfizer monitored top search results for the query "buy Viagra" on the two leading Internet search engines in March 2011. Orders were placed from 22 unique Web sites claiming to sell Viagra manufactured by Pfizer. Tablets received were assessed for chemical composition. No Web site examined required a prescription for purchase or a health screening survey; 90% offered illegal "generic Viagra." Cost per tablet ranged from $3.28-$33.00. Shipment origins of purchases were Hong Kong (N = 11), the United States (N = 6), and the United Kingdom (N = 2) as well as Canada, China, and India (N = 1 each). Notably, the four Internet pharmacies claiming to be Canadian did not ship medication from a Canadian address. Of 22 sample tablets examined, 17 (77%) were counterfeit, 4 (18%) were authentic, and 1 (5%) was an illegal generic. Counterfeit tablets were analyzed for sildenafil citrate, the active pharmaceutical ingredient (API) of Viagra, and contents varied between 30% and 50% of the label claim. Counterfeits lacked product information leaflets, including appropriate safety warnings, and genuine Viagra formulations. Internet sites claiming to sell authentic Viagra shipped counterfeit medication 77% of the time; counterfeits usually came from non-U.S. addresses and had 30% to 50% of the labeled API claim. Caution is warranted when purchasing Viagra via the Internet. © 2012 International Society for Sexual Medicine.

  7. Worldwide, 3-Year, Post-Marketing Surveillance Experience with Tofacitinib in Rheumatoid Arthritis.

    Science.gov (United States)

    Cohen, Stanley; Curtis, Jeffrey R; DeMasi, Ryan; Chen, Yan; Fan, Haiyun; Soonasra, Arif; Fleischmann, Roy

    2018-06-01

    Post-marketing surveillance (PMS) is an integral part of monitoring adverse events (AEs) following approval of new drugs. Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). An analysis of PMS reports was conducted to evaluate the safety of tofacitinib in a post-marketing setting. Worldwide tofacitinib PMS data received in the Pfizer safety database from November 6, 2012 (first marketing authorization of tofacitinib) to November 5, 2015 were analyzed. Serious AEs (SAEs) of interest were reviewed and reporting rates (RRs) were calculated by dividing the number of SAEs by the estimated 100 patient-years of exposure. Patient exposure was calculated based on estimated worldwide sales and an estimated daily regimen of tofacitinib 5 mg twice daily. During the 3-year reporting period, worldwide post-marketing exposure to tofacitinib since approval was estimated to be 34,223 patient-years. In total, 9291 case reports (82.9% non-serious) were received and 25,417 AEs, 102 fatal cases, and 4352 SAEs were reported. The RRs (per 100 patient-years) for SAEs of interest by Medical Dictionary for Regulatory Activities System Organ Class were 2.57 for infections, 0.91 for gastrointestinal disorders, 0.60 for respiratory disorders, 0.45 for neoplasms, 0.43 for cardiac disorders, and 0.12 for hepatobiliary disorders. Although there are limitations to these data, no new safety risks were revealed in this real-world setting compared with the safety profile identified in the tofacitinib RA clinical development program. Any risks identified through the tofacitinib development program and PMS will continue to be monitored through pharmacovigilance surveillance. Pfizer Inc.

  8. Patient preferences in the treatment of diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Wirostko B

    2011-05-01

    Full Text Available Barbara Wirostko1, Kathleen Beusterien2, Jessica Grinspan2, Thomas Ciulla3, John Gonder4, Alexandra Barsdorf1, Andreas Pleil51Pfizer, New York, NY, USA; 2Oxford Outcomes, Bethesda, MD, USA; 3Midwest Eye Institute, Indianapolis, IN, USA; 4Ivey Eye Institute, London, Ontario, Canada; 5Pfizer Inc, San Diego, CA, USAObjective: Accounting for patient preferences may be especially important in diabetes mellitus, given the challenge in identifying factors associated with treatment adherence. Although preference studies have been performed in diabetes, none have examined treatments used in diabetic retinopathy (DR. The objective of this study was to elicit patient preferences for attributes associated with antivascular endothelial growth factor, focal and panretinal laser, and steroid therapy used in DR management.Methods: A cross-sectional conjoint survey was administered to DR patients at three Canadian eye centers. The survey involved making tradeoffs among 11 DR treatment attributes, including the chance of improving vision and risks of adverse events over a 1-year treatment period. Attribute utilities were summed for each product profile to determine the most preferred treatment.Results: Based on the results from 161 patients, attributes affecting visual functioning, including improving visual acuity and reducing adverse events (eg, chance of cataracts, were more important than those not directly affecting vision (eg, administration. Overall, 52%, 20%, 17%, and 11% preferred the product profiles matching to the antivascular endothelial growth factor, steroid, focal laser, and panretinal laser therapies. Preferences did not vary substantially by previous treatment experience, age, or type of DR (macular edema, proliferative DR, both or neither, with the exception that more macular edema only patients preferred focal laser over steroid treatment (19% versus 14%, respectively.Conclusions: When considering the potential effects of treatment over a 1

  9. Safety and tolerability of varenicline tartrate (Champix(®)/Chantix(®)) for smoking cessation in HIV-infected subjects: a pilot open-label study.

    Science.gov (United States)

    Cui, Qu; Robinson, Linda; Elston, Dawn; Smaill, Fiona; Cohen, Jeffrey; Quan, Corinna; McFarland, Nancy; Thabane, Lehana; McIvor, Andrew; Zeidler, Johannes; Smieja, Marek

    2012-01-01

    The prevalence of smoking in HIV-infected subjects is high. As a smoking cessation aid, varenicline (Champix(®), Pfizer, Saint-Laurent, QC, Canada or Chantix(®), Pfizer, Mission, KS) has not been previously evaluated in HIV-infected smokers. In this multicenter pilot open label study, varenicline 1.0 mg was used twice daily for 12 weeks with dose titration in the first week. Adverse events (AEs) during the treatment period were recorded. Changes from baseline in laboratory tests, vital signs, daily cigarette consumption, nicotine dependence, and withdrawal were measured through week 24. Self-reported abstinence was validated by serum cotinine at week 12. We enrolled 36 subjects with a mean of 29 pack-years of smoking and a minimum of 4 cigarettes per day. All but 1 were male, 33 (92%) were white. The most frequently reported AEs were nausea (33%), abnormal dreams (31%), affect lability (19%), and insomnia (19%). Six (17%) subjects discontinued varenicline due to AEs. No grade 3/4 laboratory abnormalities or serious AEs occurred during the study. There was no significant change in HIV viral load. CD4 counts increased by 69 cells/mm3 (p = 0.001) at week 24. Serum cotinine-verified 4-week continuous abstinence rate through weeks 9-12 was 42% (95% confidence interval [CI]: 26-58%). AEs and abstinence rates were comparable to those in published randomized controlled trials conducted in generally healthy HIV-negative smokers. Varenicline was safe and appears effective among HIV-infected smokers in this exploratory study, although AEs were common. The most common AE was nausea, with no adverse effect on HIV treatment outcome. Close monitoring of liver enzymes and blood pressure is recommended for HIV-positive smokers taking varenicline.

  10. Safety and Tolerability of Varenicline Tartrate (Champix®/Chantix®) for Smoking Cessation in HIV-Infected Subjects: A Pilot Open-Label Study

    Science.gov (United States)

    Robinson, Linda; Elston, Dawn; Smaill, Fiona; Cohen, Jeffrey; Quan, Corinna; McFarland, Nancy; Thabane, Lehana; McIvor, Andrew; Zeidler, Johannes; Smieja, Marek

    2012-01-01

    Abstract The prevalence of smoking in HIV-infected subjects is high. As a smoking cessation aid, varenicline (Champix®, Pfizer, Saint-Laurent, QC, Canada or Chantix®, Pfizer, Mission, KS) has not been previously evaluated in HIV-infected smokers. In this multicenter pilot open label study, varenicline 1.0 mg was used twice daily for 12 weeks with dose titration in the first week. Adverse events (AEs) during the treatment period were recorded. Changes from baseline in laboratory tests, vital signs, daily cigarette consumption, nicotine dependence, and withdrawal were measured through week 24. Self-reported abstinence was validated by serum cotinine at week 12. We enrolled 36 subjects with a mean of 29 pack-years of smoking and a minimum of 4 cigarettes per day. All but 1 were male, 33 (92%) were white. The most frequently reported AEs were nausea (33%), abnormal dreams (31%), affect lability (19%), and insomnia (19%). Six (17%) subjects discontinued varenicline due to AEs. No grade 3/4 laboratory abnormalities or serious AEs occurred during the study. There was no significant change in HIV viral load. CD4 counts increased by 69 cells/mm3 (p=0.001) at week 24. Serum cotinine-verified 4-week continuous abstinence rate through weeks 9–12 was 42% (95% confidence interval [CI]: 26–58%). AEs and abstinence rates were comparable to those in published randomized controlled trials conducted in generally healthy HIV-negative smokers. Varenicline was safe and appears effective among HIV-infected smokers in this exploratory study, although AEs were common. The most common AE was nausea, with no adverse effect on HIV treatment outcome. Close monitoring of liver enzymes and blood pressure is recommended for HIV-positive smokers taking varenicline. PMID:22007690

  11. Media coverage of off-label promotion: a content analysis of US newspapers.

    Science.gov (United States)

    Joshi, Avani D; Patel, Dipen A; Holdford, David A

    2011-09-01

    Promotion of drugs for off-label use is newsworthy, because it is an illegal but all too common strategy used by pharmaceutical companies. The print media are an important source of information about coverage of off-label promotion of drugs and devices and can influence public perceptions of the practice. Print media coverage of off-label promotion during the years 1990-2008 were described and quantified. The primary themes and general tones relating to off-label promotion articles were evaluated. General concerns associated with off-label promotion and complaints about specific brand name drugs were also identified. Content analyses of the top 6 US newspapers were conducted over the period of 1990-2008 to analyze the media coverage given to off-label promotion of drugs and devices. Headlines and full text of articles were analyzed for primary themes and tones of the coverage. Intercoder reliability tests were performed on all the study variables. One hundred and one articles were identified meeting the study inclusion criteria. Coverage varied by newspaper. The Wall Street Journal had the most coverage on the topic (45%), and USA Today and Chicago Tribune had the least coverage (5%). Overall, most of the stories sampled were deemed to have a negative tone in coverage (77%), focusing mainly on lawsuits against drug companies for promoting their drugs for off-label uses. Pfizer's Neurontin(®) (Pfizer Inc., New York, NY 10017, USA) and Johnson & Johnson's Retin-A(®) (Orthoneutrogena, Los Angeles, CA 90045, USA) received the most media attention. The news media helps shape public understanding of promotional practices of pharmaceutical companies and their potential benefits and harms. This study suggests that print media coverage is generally negative about off-label promotion, focusing on legal actions taken against drug companies and the negative consequences of such promotional practices. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. High-resolution structure of a retroviral protease folded as a monomer

    International Nuclear Information System (INIS)

    Gilski, Miroslaw; Kazmierczyk, Maciej; Krzywda, Szymon; Zábranská, Helena; Cooper, Seth; Popović, Zoran; Khatib, Firas; DiMaio, Frank; Thompson, James; Baker, David; Pichová, Iva; Jaskolski, Mariusz

    2011-01-01

    The crystal structure of Mason–Pfizer monkey virus protease folded as a monomer has been solved by molecular replacement using a model generated by players of the online game Foldit. The structure shows at high resolution the details of a retroviral protease folded as a monomer which can guide rational design of protease dimerization inhibitors as retroviral drugs. Mason–Pfizer monkey virus (M-PMV), a D-type retrovirus assembling in the cytoplasm, causes simian acquired immunodeficiency syndrome (SAIDS) in rhesus monkeys. Its pepsin-like aspartic protease (retropepsin) is an integral part of the expressed retroviral polyproteins. As in all retroviral life cycles, release and dimerization of the protease (PR) is strictly required for polyprotein processing and virion maturation. Biophysical and NMR studies have indicated that in the absence of substrates or inhibitors M-PMV PR should fold into a stable monomer, but the crystal structure of this protein could not be solved by molecular replacement despite countless attempts. Ultimately, a solution was obtained in mr-rosetta using a model constructed by players of the online protein-folding game Foldit. The structure indeed shows a monomeric protein, with the N- and C-termini completely disordered. On the other hand, the flap loop, which normally gates access to the active site of homodimeric retropepsins, is clearly traceable in the electron density. The flap has an unusual curled shape and a different orientation from both the open and closed states known from dimeric retropepsins. The overall fold of the protein follows the retropepsin canon, but the C α deviations are large and the active-site ‘DTG’ loop (here NTG) deviates up to 2.7 Å from the standard conformation. This structure of a monomeric retropepsin determined at high resolution (1.6 Å) provides important extra information for the design of dimerization inhibitors that might be developed as drugs for the treatment of retroviral infections

  13. Twelve years' experience with direct-to-consumer advertising of prescription drugs in Canada: a cautionary tale.

    Directory of Open Access Journals (Sweden)

    Barbara Mintzes

    2009-05-01

    Full Text Available Direct-to-consumer advertising (DTCA of prescription drugs is illegal in Canada as a health protection measure, but is permitted in the United States. However, in 2000, Canadian policy was changed to allow 'reminder' advertising of prescription drugs. This is a form of advertising that states the brand name without health claims. 'Reminder' advertising is prohibited in the US for drugs that have 'black box' warnings of serious risks. This study examines spending on DTCA in Canada from 1995 to 2006, 12 years spanning this policy shift. We ask how annual per capita spending compares to that in the US, and whether drugs with Canadian or US regulatory safety warnings are advertised to the Canadian public in reminder advertising.Prescription drug advertising spending data were extracted from a data set on health sector spending in Canada obtained from a market research company, TNS Media Inc. Spending was adjusted for inflation and compared with US spending. Inflation-adjusted spending on branded DTCA in Canada grew from under CAD$2 million per year before 1999 to over $22 million in 2006. The major growth was in broadcast advertising, accounting for 83% of spending in 2006. US annual per capita spending was on average 24 times Canadian levels. Celebrex (celecoxib, which has a US black box and was subject to three safety advisories in Canada, was the most heavily advertised drug on Canadian television in 2005 and 2006. Of 8 brands with >$500,000 spending, which together accounted for 59% of branded DTCA in all media, 6 were subject to Canadian safety advisories, and 4 had US black box warnings.Branded 'reminder' advertising has grown rapidly in Canada since 2000, mainly due to a growth in television advertising. Although DTCA spending per capita is much lower in Canada than in the US, there is no evidence of safer content or product choice; many heavily-advertised drugs in Canada have been subject to safety advisories. For governments searching for

  14. Twelve years' experience with direct-to-consumer advertising of prescription drugs in Canada: a cautionary tale.

    Science.gov (United States)

    Mintzes, Barbara; Morgan, Steve; Wright, James M

    2009-05-27

    Direct-to-consumer advertising (DTCA) of prescription drugs is illegal in Canada as a health protection measure, but is permitted in the United States. However, in 2000, Canadian policy was changed to allow 'reminder' advertising of prescription drugs. This is a form of advertising that states the brand name without health claims. 'Reminder' advertising is prohibited in the US for drugs that have 'black box' warnings of serious risks. This study examines spending on DTCA in Canada from 1995 to 2006, 12 years spanning this policy shift. We ask how annual per capita spending compares to that in the US, and whether drugs with Canadian or US regulatory safety warnings are advertised to the Canadian public in reminder advertising. Prescription drug advertising spending data were extracted from a data set on health sector spending in Canada obtained from a market research company, TNS Media Inc. Spending was adjusted for inflation and compared with US spending. Inflation-adjusted spending on branded DTCA in Canada grew from under CAD$2 million per year before 1999 to over $22 million in 2006. The major growth was in broadcast advertising, accounting for 83% of spending in 2006. US annual per capita spending was on average 24 times Canadian levels. Celebrex (celecoxib), which has a US black box and was subject to three safety advisories in Canada, was the most heavily advertised drug on Canadian television in 2005 and 2006. Of 8 brands with >$500,000 spending, which together accounted for 59% of branded DTCA in all media, 6 were subject to Canadian safety advisories, and 4 had US black box warnings. Branded 'reminder' advertising has grown rapidly in Canada since 2000, mainly due to a growth in television advertising. Although DTCA spending per capita is much lower in Canada than in the US, there is no evidence of safer content or product choice; many heavily-advertised drugs in Canada have been subject to safety advisories. For governments searching for compromise

  15. Downregulation of survivin expression and concomitant induction of apoptosis by celecoxib and its non-cyclooxygenase-2-inhibitory analog, dimethyl-celecoxib (DMC, in tumor cells in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Hofman Florence M

    2006-05-01

    Full Text Available Abstract Background 2,5-Dimethyl-celecoxib (DMC is a close structural analog of the selective cyclooxygenase-2 (COX-2 inhibitor celecoxib (Celebrex® that lacks COX-2-inhibitory function. However, despite its inability to block COX-2 activity, DMC is able to potently mimic the anti-tumor effects of celecoxib in vitro and in vivo, indicating that both of these drugs are able to involve targets other than COX-2 to exert their recognized cytotoxic effects. However, the molecular components that are involved in mediating these drugs' apoptosis-stimulatory consequences are incompletely understood. Results We present evidence that celecoxib and DMC are able to down-regulate the expression of survivin, an anti-apoptotic protein that is highly expressed in tumor cells and known to confer resistance of such cells to anti-cancer treatments. Suppression of survivin is specific to these two drugs, as other coxibs (valdecoxib, rofecoxib or traditional NSAIDs (flurbiprofen, indomethacin, sulindac do not affect survivin expression at similar concentrations. The extent of survivin down-regulation by celecoxib and DMC in different tumor cell lines is somewhat variable, but closely correlates with the degree of drug-induced growth inhibition and apoptosis. When combined with irinotecan, a widely used anticancer drug, celecoxib and DMC greatly enhance the cytotoxic effects of this drug, in keeping with a model that suppression of survivin may be beneficial to sensitize cancer cells to chemotherapy. Remarkably, these effects are not restricted to in vitro conditions, but also take place in tumors from drug-treated animals, where both drugs similarly repress survivin, induce apoptosis, and inhibit tumor growth in vivo. Conclusion In consideration of survivin's recognized role as a custodian of tumor cell survival, our results suggest that celecoxib and DMC might exert their cytotoxic anti-tumor effects at least in part via the down-regulation of survivin – in a

  16. Twelve Years' Experience with Direct-to-Consumer Advertising of Prescription Drugs in Canada: A Cautionary Tale

    Science.gov (United States)

    Mintzes, Barbara; Morgan, Steve; Wright, James M.

    2009-01-01

    Background Direct-to-consumer advertising (DTCA) of prescription drugs is illegal in Canada as a health protection measure, but is permitted in the United States. However, in 2000, Canadian policy was changed to allow ‘reminder’ advertising of prescription drugs. This is a form of advertising that states the brand name without health claims. ‘Reminder’ advertising is prohibited in the US for drugs that have ‘black box’ warnings of serious risks. This study examines spending on DTCA in Canada from 1995 to 2006, 12 years spanning this policy shift. We ask how annual per capita spending compares to that in the US, and whether drugs with Canadian or US regulatory safety warnings are advertised to the Canadian public in reminder advertising. Methodology/Principal Findings Prescription drug advertising spending data were extracted from a data set on health sector spending in Canada obtained from a market research company, TNS Media Inc. Spending was adjusted for inflation and compared with US spending. Inflation-adjusted spending on branded DTCA in Canada grew from under CAD$2 million per year before 1999 to over $22 million in 2006. The major growth was in broadcast advertising, accounting for 83% of spending in 2006. US annual per capita spending was on average 24 times Canadian levels. Celebrex (celecoxib), which has a US black box and was subject to three safety advisories in Canada, was the most heavily advertised drug on Canadian television in 2005 and 2006. Of 8 brands with >$500,000 spending, which together accounted for 59% of branded DTCA in all media, 6 were subject to Canadian safety advisories, and 4 had US black box warnings. Conclusions/Significance Branded ‘reminder’ advertising has grown rapidly in Canada since 2000, mainly due to a growth in television advertising. Although DTCA spending per capita is much lower in Canada than in the US, there is no evidence of safer content or product choice; many heavily-advertised drugs in Canada have

  17. COX-2 inhibition is neither necessary nor sufficient for celecoxib to suppress tumor cell proliferation and focus formation in vitro

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    Petasis Nicos A

    2008-05-01

    Full Text Available Abstract Background An increasing number of reports is challenging the notion that the antitumor potential of the selective COX-2 inhibitor celecoxib (Celebrex® is mediated primarily via the inhibition of COX-2. We have investigated this issue by applying two different analogs of celecoxib that differentially display COX-2-inhibitory activity: the first analog, called unmethylated celecoxib (UMC, inhibits COX-2 slightly more potently than its parental compound, whereas the second analog, 2,5-dimethyl-celecoxib (DMC, has lost the ability to inhibit COX-2. Results With the use of glioblastoma and pancreatic carcinoma cell lines, we comparatively analyzed the effects of celecoxib, UMC, and DMC in various short-term (≤48 hours cellular and molecular studies, as well as in long-term (≤3 months focus formation assays. We found that DMC exhibited the most potent antitumor activity; celecoxib was somewhat less effective, and UMC clearly displayed the overall weakest antitumor potential in all aspects. The differential growth-inhibitory and apoptosis-stimulatory potency of these compounds in short-term assays did not at all correlate with their capacity to inhibit COX-2, but was closely aligned with their ability to trigger endoplasmic reticulum stress (ERS, as indicated by the induction of the ERS marker CHOP/GADD153 and activation of the ERS-associated caspase 7. In addition, we found that these compounds were able to restore contact inhibition and block focus formation during long-term, chronic drug exposure of tumor cells, and this was achieved at sub-toxic concentrations in the absence of ERS or inhibition of COX-2. Conclusion The antitumor activity of celecoxib in vitro did not involve the inhibition of COX-2. Rather, the drug's ability to trigger ERS, a known effector of cell death, might provide an alternative explanation for its acute cytotoxicity. In addition, the newly discovered ability of this drug to restore contact inhibition and

  18. The Story of Azithromycin

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    Banić Tomišić, Z.

    2011-12-01

    Full Text Available The invention of azithromycin (1, Figure 1, the active pharmaceutical ingredient of the antibiotic Sumamed (Croatian brand name by PLIVA; Zithromax by Pfizer in the USA belongs among the great achievements in the history of science in Croatia. From the viewpoint of commercialization of research results, it may have been one of the greatest. In addition to contributing to science and to medicine, azithromycin has also brought about an improvement in the quality of life on the global level. Owing to its exceptional therapeutic properties, it has come to be one of the most successful antibiotics worldwide. Marking the 30th anniversary of the azithromycin Yugoslav patent application, this paper gives an overview of the research that led to its discovery and comes with a list of papers and patents through which the drug has been made known to the public (Table 1, Figures 4 and 6. The invention was due to the scientists from the Research Institute of the pharmaceutical company PLIVA in Zagreb, Croatia, D. Sc. S. Đokić, M. Sc. G. Kobrehel, D. Sc. G. Lazarevski, and D. Sc. Z. Tamburašev (Figure 3. Azithromycin became the first representative of the new class of 15-membered macrolides known as azalides after the introduction of nitrogen in the macrocycle of erythromycin A (2, Figure 1. Its synthesis involved several steps (Figure 2: oximation of erithromycin A, Beckmann rearrangement of erythromycin A oxime with aromatic sulphochlorides, reduction of the produced erithromycin A iminoether, and final methylation of the nitrogen introduced in the macrocycle of erythromycin A. Because of inadequate analytical support in the late 1970s and early 1980s, the precise structure of the LD product (Figure 5 in the Beckmann rearrangement step of azithromycin synthesis was confirmed only later as 7 and not 6 as assumed (Figure 5. Today, azithromycin is known under the common chemical name of 9-deoxo-9a-aza-9a-methyl-homoerythromycin A. This paper also deals with

  19. Real-World Analysis of Dispensed IUs of Coagulation Factor IX and Resultant Expenditures in Hemophilia B Patients Receiving Standard Half-life Versus Extended Half-life Products and Those Switching from Standard Half-life to Extended Half-life Products.

    Science.gov (United States)

    Tortella, Bartholomew J; Alvir, José; McDonald, Margaret; Spurden, Dean; Fogarty, Patrick F; Chhabra, Amit; Pleil, Andreas M

    2018-01-24

    median IUs dispensed increased by 4,775 IU. Factor replacement expenditures were higher after switching from the SHL to the EHL product in each of the 3-month periods examined before versus after the switch. This analysis of real-world data showed that switching from the SHL to the EHL product was associated with higher expenditures. Increased expenditures noted in the first 3 months after switching may be related to initial stocking up of the EHL product, but expenditures were sustained throughout the 1-year period of data analysis. Further analysis of these findings with larger numbers of patients should be explored. This study was sponsored by Pfizer. Pfizer employees were involved in the study design; the collection, analysis, and interpretation of data; the review of the manuscript; and the decision to submit for publication. All authors are employees of Pfizer. No author received an honorarium or other form of payment related to the development of this manuscript. All authors participated in the study design, data interpretation, and manuscript review and revisions and granted approval for the submission of the manuscript. Alvir, McDonald, and Tortella also participated in data analysis. Data from this paper were presented in part at the European Association for Haemophilia and Allied Disorders Annual Meeting, February 1-3, 2017, Paris, France; at the International Society for Pharmacoeconomics and Outcomes Research Annual Meeting, May 20-24, 2017, Boston, Massachusetts; and at the International Society on Thrombosis and Haemostasis Congress, July 8-13, 2017, Berlin, Germany.

  20. Recombinant TSH (Thyrogen) administration to a patient with metastatic well differentiated thyroid carcinoma in whom six weeks of T-4 withdrawal led to a sub-optimal TSH response

    International Nuclear Information System (INIS)

    Tenorio, L.E.; Achong, D.; Bidot, P.

    2002-01-01

    Objectives: A 72 y.o. white man was diagnosed with follicular thyroid carcinoma in 1991. He was partially treated with partial thyroidectomy. Pulmonary nodules evident on Radiograph were explained to the patient as 'benign in nature'. No I-131 therapy or follow up was scheduled. Seven years later, the pulmonary nodules proved to be metastatic thyroid carcinoma. Endogenous TSH levels failed to raise following T-4 withdrawal, most likely secondary to endogenous production of T-4 by metastatic cancer. Recombinant TSH (Thyrogen) stimulation before I-131 therapy was considered to improve I-131 tumor uptake. Materials and method: In an emergency room visit in June 1997 for an unrelated condition, a chest X-rays detected pulmonary nodules. He had no dyspnea, no hemoptysis, and no chest pain. CT guided biopsy demonstrated metastatic thyroid carcinoma. Pleural fluid was positive for presence of Thyroglobulin. Left hemi-thyroidectomy was performed on September 1997. His TSH was 14 mIU/mL six weeks after T-4 withdrawal. Serum thyroglobulin (sTG) level was 10100 ng/mL on 10/20/97 (Nl. less than 0.5 mIU/mL), Antithyroglobulin antibody test was negative. A Thallium-201 whole body scan demonstrated mild pulmonary uptake similar to the chest X-Rays findings (the lesser the Tl-210 uptake by the tumor, the better the response to I-131). The patient was enrolled in a compassionate use protocol for Thyrogen. Thyrogen 0.9 mg q/24h was administered. Results: The TSH after each dose of Thyrogen was > 100 mIU/mL. 199.7 mCi of I-131 were administered orally. A post therapy whole body scan (WBS) demonstrated multiple functional metastases in both lungs, some of them not shown in the previous Tl-201 scan. His sTG dropped to 2515 ng/mL on 1/29/1998, and a CT demonstrated reduction in size of the pulmonary nodules. A Tl-201 WBS dated 6/1/98 showed uptake in the left hilar region, with poor uptake in previously positive Tl-201 nodules. However, follow up Tl-201 demonstrated progressive

  1. Peptide dendrimer-conjugates of ketoprofen: Synthesis and ex vivo and in vivo evaluations of passive diffusion, sonophoresis and iontophoresis for skin delivery.

    Science.gov (United States)

    Hegde, Aswathi R; Rewatkar, Prarthana V; Manikkath, Jyothsna; Tupally, Karnaker; Parekh, Harendra S; Mutalik, Srinivas

    2017-05-01

    The aim of this study was to evaluate skin delivery of ketoprofen when covalently tethered to mildly cationic (2 + or 4 + ) peptide dendrimers prepared wholly by solid phase peptide synthesis. The amino acids glycine, arginine and lysine formed the dendrimer with ketoprofen tethered either to the lysine side-arm (N ε ) or periphery of dendrimeric branches. Passive diffusion, sonophoresis- and iontophoresis-assisted permeation of each peptide dendrimer-drug conjugate (D1-D4) was studied across mouse skin, both in vitro and in vivo. In addition, skin toxicity of dendrimeric conjugates when trialed with iontophoresis or sonophoresis was also evaluated. All dendrimeric conjugates improved aqueous solubility at least 5-fold, compared to ketoprofen alone, while also exhibiting appreciable lipophilicity. In vitro passive diffusion studies revealed that ketoprofen in its native form was delivered to a greater extent, compared with a dendrimer-conjugated form at the end of 24h (Q 24h (μg/cm 2 ): ketoprofen (68.06±3.62)>D2 (49.62±2.92)>D4 (19.20±0.89)>D1 (6.45±0.40)>D3 (2.21±0.19). However, sonophoresis substantially increased the skin permeation of ketoprofen-dendrimer conjugates in 30min (Q 30min (μg/cm 2 ): D4 (122.19±7.14)>D2 (66.74±3.86)>D1 (52.10±3.22)>D3 (41.66±3.22)) although ketoprofen alone again proved superior (Q 30min : 167.99±9.11μg/cm 2 ). Next, application of iontophoresis was trialed and shown to considerably increase permeation of dendrimeric ketoprofen in 6h (Q 6h (μg/cm 2 ): D2 (711.49±39.14)>D4 (341.23±16.43)>D3 (89.50±4.99)>D1 (50.91±2.98), with a Q 6h value of 96.60±5.12μg/cm 2 for ketoprofen alone). In vivo studies indicated that therapeutically relevant concentrations of ketoprofen could be delivered transdermally when iontophoresis was paired with D2 (985.49±43.25ng/mL). Further, histopathological analysis showed that the dendrimeric approach was a safe mode as ketoprofen alone. The present study successfully demonstrates that

  2. Skin permeability and pharmacokinetics of diclofenac epolamine administered by dermal patch in Yorkshire-Landrace pigs

    Directory of Open Access Journals (Sweden)

    Tse S

    2012-10-01

    Full Text Available Susanna Tse,1 Kendall D Powell,2 Stephen MacLennan,3 Allan R Moorman,4 Craig Paterson,5 Rosonald R Bell11Pfizer Inc, Groton, CT, USA; 2Tandem Labs, Durham, NC, USA; 3BioCryst Pharmaceuticals Inc, Durham, NC, USA; 4Alta Vetta Pharmaceutical Consulting LLC, Durham, NC, USA; 5Salix Pharmaceuticals Inc, Raleigh, NC, USAPurpose: This study compared the pharmacokinetic profile, and systemic and local absorption of diclofenac, following dermal patch application and oral administration in Yorkshire- Landrace pigs.Patients and methods: Twelve anesthetized, female, Yorkshire-Landrace pigs were randomized to receive either the dermal patch (FLECTOR® patch, 10 × 14 cm; Alpharma Pharmaceuticals, a subsidiary of Pfizer Inc, New York, NY or 50 mg oral diclofenac (Voltaren®; Novartis, East Hanover, NJ. Tissue (skin area of 2 × 2 cm and underlying muscles approximately 2–3 cm in depth and blood (10 mL samples were collected at timed intervals up to 11.5 hours after initial patch application or oral administration. The concentrations of diclofenac in plasma, skin, and muscle samples were analyzed using validated ultra performance liquid chromatography tandem mass spectrometric methods.Results: Peak systemic exposure of diclofenac was very low by dermal application compared with oral administration (maximum concentration [Cmax] values of 3.5 vs 9640 ng/mL, respectively. Absorption of diclofenac into underlying muscles beneath the dermal patch was sustained, and followed apparently zero-order kinetics, with the skin serving as a depot with elevated concentrations of diclofenac. Concentrations of diclofenac in muscles beneath the patch application site were similar to corresponding tissues after oral administration (Cmax values of 879 and 1160 ng/mL, respectively. In contrast to the wide tissue distribution of diclofenac after oral administration, dermal patch application resulted in high concentrations of diclofenac only on the treated skin and immediate

  3. Pregabalin for the treatment of postoperative pain: results from three controlled trials using different surgical models

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    Singla NK

    2014-12-01

    Full Text Available Neil K Singla,1 Jacques E Chelly,2 David R Lionberger,3 Joseph Gimbel,4 Luis Sanin,5 Jonathan Sporn,5 Ruoyong Yang,5 Raymond Cheung,5 Lloyd Knapp,6 Bruce Parsons5 1Lotus Clinical Research, Pasadena, CA, USA; 2Division of Acute Interventional Perioperative Pain, Department of Anesthesiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 3Department of Orthopedic Surgery, Baylor College of Medicine, Houston, TX, USA; 4Arizona Research Center, Phoenix, AZ, USA; 5Pfizer Inc., New York, NY, USA; 6Pfizer Inc., New London, CT, USA Purpose: To evaluate the efficacy and safety of pregabalin (150 or 300 mg/d as an adjunctive therapy for the treatment of postoperative pain. Patients and methods: This study reports findings from three separate, multicenter, randomized, double-blind, placebo-controlled trials of adjunctive pregabalin for the treatment of postoperative pain. Patients underwent one of three categories of surgical procedures (one procedure per study: elective inguinal hernia repair (post-IHR; elective total knee arthroplasty (post-TKA; or total abdominal hysterectomy (posthysterectomy. The primary endpoint in each trial, mean worst pain over the past 24 hours, was assessed 24 hours post-IHR and posthysterectomy, and 48 hours post-TKA. Patients rated their pain on a scale from 0 to 10, with higher scores indicating greater pain severity. Results: In total, 425 (post-IHR, 307 (post-TKA, and 501 (posthysterectomy patients were randomized to treatment. There were no statistically significant differences between the pregabalin and placebo groups with respect to the primary endpoint in any of the three trials. The least squares mean difference in worst pain, between 300 mg/d pregabalin and placebo, was -0.7 (95% confidence interval [CI] =-1.4, -0.1; Hochberg adjusted P=0.067 post-IHR; -0.34 (95% CI =-1.07, 0.39; P=0.362 post-TKA; and -0.2 (95% CI =-0.66, 0.31; P=0.471 posthysterectomy. Conclusion: There were no significant differences

  4. Improvement in erection hardness and intercourse success with first dose of sildenafil citrate 100 mg

    Directory of Open Access Journals (Sweden)

    Mulhall JP

    2013-11-01

    Full Text Available John P Mulhall,1 Dana L Creanga,2 Vera J Stecher31Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 2Consultant to Pfizer Inc., New York, NY, USA; 3Medical Affairs, Primary Care Business Unit, Pfizer Inc., New York, NY, USAPurpose: To determine, in men with erectile dysfunction (ED, the extent of improvement in erection hardness and in the rate of successful sexual intercourse (SSI during the final intercourse attempt using sildenafil 50 mg compared with the subsequent initial attempt after a dose increase to 100 mg.Patients and methods: This post hoc analysis used data from two randomized, double-blind, placebo-controlled studies of flexible-dose sildenafil for the treatment of men with ED, who were given sildenafil 50 mg or matching placebo, to be taken as needed before sexual intercourse. After 2 weeks, those with no tolerability concerns were titrated up to 100 mg, forming the subgroup of this analysis. The main outcome measures were event log data, including an Erection Hardness Score (EHS and a question on SSI (“Did your erection last long enough for you to have successful sexual intercourse?”, for each attempt at sexual intercourse, analyzed by study and treatment group (sildenafil or placebo. Statistical comparisons were conducted by using the Fisher's exact test.Results: In both studies, the sildenafil group had a larger proportion of EHS4 (completely hard and fully rigid erections (P < 0.001 and SSI (P < 0.005 compared with the placebo group, both before and after the dose increase. Between the final 50 mg sildenafil dose and the initial 100 mg sildenafil dose, the outcomes improved and significantly so in the larger study.Conclusion: The improved efficacy with sildenafil 100 mg versus 50 mg, which occurs rapidly, suggests that patients should be encouraged to use 100 mg if they are unable to achieve completely hard and fully rigid erections or SSI with the 50 mg dose

  5. Stable Isotope Profiling of Internet-Sourced Viagra® and 'generic- Viagra' Tablets

    Science.gov (United States)

    Kemp, Helen; Meier-Augenstein, Wolfram

    2013-04-01

    Viagra® manufactured by Pfizer was the first prescription drug for the treatment of erectile dysfunction (ED), a condition that is estimated to affect 1 in 10 men at some stage in their lives (1). Viagra® contains the active pharmaceutical ingredient (API) sildenafil, as the citrate salt. Sildenafil, along with Tadalafil and Vardenafil belong to a class of drugs known as phosphodiesterase type 5 (PDE5) inhibitors. Since its first production in 1998, Viagra® has generated well in excess of 10 billion US dollars in sales (2) and with Pfizers' patent extended to April 2020 (3) it still remains the only sildenafil-based treatment option for sufferers of ED in the US. There are no legal 'generic-Viagra' formulations available in the US. However, formulations containing sildenafil citrate as API are widely available over the internet and often sold as 'generic Viagra'. These cheaper alternatives are often manufactured under less than ideal conditions with little or no QA/QC procedures in place. The World Health Organisation recognised the scale of the problem in its 2010 bulletin "Growing threat from counterfeit medicines" (4) and quotes a Dutch study cited in the International Journal of Clinical Practice in which from a cohort of 370 seized Viagra® samples, only 10 were genuine. We sourced a variety of tablets sold for the treatment of ED which claimed to have sildenafil citrate as API. Viagra®, 'generic-Viagra', Kamagra, Silagra and Filagra tablets were ordered via the internet and supplied from both UK-based pharmacies as well as overseas suppliers (Hong Kong, India, Vanuata). In this small-scale pilot study, we present results from bulk 2H/18O and 13C/15N stable isotope analysis performed on crushed tablets from 23 samples of internet-sourced tablets sold for the treatment of ED and purported to contain sildenafil citrate as API. References 1. www.healthcare.org.uk 2. www.moneynews.com 3. US Patent & trademark office (www.uspto.gov) 4. WHO bulletin 2010; 88:247-248

  6. Antiplatelet Therapy and Clinical Outcomes Following Myocardial Infarction Among Patients in a U.S. Employer-Based Insurance Database.

    Science.gov (United States)

    Patel, Mehul D; Wu, David; Chase, Monica Reed; Mavros, Panagiotis; Heithoff, Kim; Hanson, Mary E; Simpson, Ross J

    2017-06-01

    opinions expressed are those of the authorship and may not necessarily reflect those of the company. Reed Chase, Wu, Mavros, Heithoff, and Hanson are employees of Merck Sharp & Dohme, a subsidiary of Merck & Co., and may own stock and/or hold stock options in the company. Patel was an employee of Merck & Co. during the conduct of this study and preparation of the manuscript. Simpson is a paid consultant for Merck, Pfizer, and Amgen and has received speaker's fees from Merck and Pfizer. Study concept and design were contributed by all authors except Hanson. Heifhoff and Patel collected the data, and data interpretation was performed by Simpson, Mavros, Patel, Wu, and Hanson. The manuscript was written by Hanson, Mavros, and Patel and revised by Heithoff, Wu, Simpson, and Reed Chase.

  7. Alcuni recenti orientamenti interpretativi in tema di intersection fra PI e Antitrust

    Directory of Open Access Journals (Sweden)

    Gustavo Ghidini

    2015-10-01

    Full Text Available Recent decisions of the European Court of Justice (Astrazeneca and Italian Antitrust Authority (Pfizer suggest that even the mere acquisition – as distinguished from the exercise – of a patent (as any other IPR may amount to a misuse if the achievement thereof runs in contrast with the rules governing its entitlement; and, if the patent owner enjoys a dominant position, such patent misuse may translate into an abuse of said position under art. 102 TFEU. Cases of this type must be clearly distinguished from those where the patent has been legitimately/regularly obtained, and its holder exercises the ‘institutionally excluding’ related power against unauthorized third parties. In such cases, antitrust law comes in not to enforce a properly ‘abusive’ conduct, but to correct an objective market situation which has grown ‘excessively’ foreclosing competition – and this, thanks to the very success of the patent. A situation, and a legal solution, which bears a strong analogy of rationale with the one envisaged by art. 2597 of Italian civil code. Thus, that of ‘abuse’ is a general normative tool that is used both to adjudicate anti-competitive torts (as in the first case and to regulate an objective ‘close to monopoly’ situation occurred without any wrongdoing by the patent holder.The distinction is confirmed by the consequences. On one side, as in Astrazeneca and Pfizer, the patent holders are sanctioned (and their patent or CCP is subject to annulment; no compensation whatever of the patentee is thinkable. On the other side, in the case of the regular acquisition and intrinsically legitimate exercise of the IPR competition law imposes a duty to license it on FRAND terms: i.e., with compensation of the patent holder, fully retains his entitlement. Here, self-evidently, the patent holder has behaved lawfully -otherwise a compensation would be unthinkable! The ‘abuse’ may properly occur ex post, i.e. only if the holder

  8. Immunogenicity, Safety, and Tolerability of Bivalent rLP2086 Meningococcal Group B Vaccine Administered Concomitantly With Diphtheria, Tetanus, and Acellular Pertussis and Inactivated Poliomyelitis Vaccines to Healthy Adolescents.

    Science.gov (United States)

    Vesikari, Timo; Wysocki, Jacek; Beeslaar, Johannes; Eiden, Joseph; Jiang, Qin; Jansen, Kathrin U; Jones, Thomas R; Harris, Shannon L; O'Neill, Robert E; York, Laura J; Perez, John L

    2016-06-01

    Concomitant administration of bivalent rLP2086 (Trumenba [Pfizer, Inc] and diphtheria, tetanus, and acellular pertussis and inactivated poliovirus vaccine (DTaP/IPV) was immunologically noninferior to DTaP/IPV and saline and was safe and well tolerated. Bivalent rLP2086 elicited robust and broad bactericidal antibody responses to diverse Neisseria meningitidis serogroup B strains expressing antigens heterologous to vaccine antigens after 2 and 3 vaccinations. Bivalent rLP2086, a Neisseria meningitidis serogroup B (MnB) vaccine (Trumenba [Pfizer, Inc]) recently approved in the United States to prevent invasive MnB disease in individuals aged 10-25 years, contains recombinant subfamily A and B factor H binding proteins (fHBPs). This study evaluated the coadministration of Repevax (diphtheria, tetanus, and acellular pertussis and inactivated poliovirus vaccine [DTaP/IPV]) (Sanofi Pasteur MSD, Ltd) and bivalent rLP2086. Healthy adolescents aged ≥11 to B proteins different from the vaccine antigens. Participants were randomly assigned to receive bivalent rLP2086 + DTaP/IPV (n = 373) or saline + DTaP/IPV (n = 376). Immune responses to DTaP/IPV in participants who received bivalent rLP2086 + DTaP/IPV were noninferior to those in participants who received saline + DTaP/IPV.The proportions of bivalent rLP2086 + DTaP/IPV recipients with prespecified seroprotective hSBA titers to the 4 MnB test strains were 55.5%-97.3% after vaccination 2 and 81.5%-100% after vaccination 3. The administration of bivalent rLP2086 was well tolerated and resulted in few serious adverse events. Immune responses to DTaP/IPV administered with bivalent rLP2086 to adolescents were noninferior to DTaP/IPV administered alone. Bivalent rLP2086 was well tolerated and elicited substantial and broad bactericidal responses to diverse MnB strains in a high proportion of recipients after 2 vaccinations, and these responses were further enhanced after 3 vaccinations.ClinicalTrials.gov identifier NCT01323270

  9. Health care utilization and expenditures among Medicaid beneficiaries with neuropathic pain following spinal cord injury

    Directory of Open Access Journals (Sweden)

    Margolis JM

    2014-07-01

    Full Text Available Jay M Margolis,1 Paul Juneau,1 Alesia Sadosky,2 Joseph C Cappelleri,3 Thomas N Bryce,4 Edward C Nieshoff5 1Truven Health Analytics, Bethesda, MD, USA; 2Pfizer Inc., New York, NY, USA; 3Pfizer Inc., Groton, CT, USA; 4Department of Rehabilitation Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY, USA; 5Department of Physical Medicine and Rehabilitation, Wayne State University School of Medicine, Detroit, MI, USA Background: The study aimed to evaluate health care resource utilization (HRU and costs for neuropathic pain (NeP secondary to spinal cord injury (SCI among Medicaid beneficiaries. Methods: The retrospective longitudinal cohort study used Medicaid beneficiary claims with SCI and evidence of NeP (SCI-NeP cohort matched with a cohort without NeP (SCI-only cohort. Patients had continuous Medicaid eligibility 6 months pre- and 12 months postindex, defined by either a diagnosis of central NeP (ICD-9-CM code 338.0x or a pharmacy claim for an NeP-related antiepileptic or antidepressant drug within 12 months following first SCI diagnosis. Demographics, clinical characteristics, HRU, and expenditures were compared between cohorts. Results: Propensity score-matched cohorts each consisted of 546 patients. Postindex percentages of patients with physician office visits, emergency department visits, SCI- and pain-related procedures, and outpatient prescription utilization were all significantly higher for SCI-NeP (P<0.001. Using regression models to account for covariates, adjusted mean expenditures were US$47,518 for SCI-NeP and US$30,150 for SCI only, yielding incremental costs of US$17,369 (95% confidence interval US$9,753 to US$26,555 for SCI-NeP. Factors significantly associated with increased cost included SCI type, trauma-related SCI, and comorbidity burden. Conclusion: Significantly higher HRU and total costs were incurred by Medicaid patients with NeP secondary to SCI compared with matched SCI-only patients. Keywords: spinal

  10. Systematic review and comparison of pharmacologic therapies for neuropathic pain associated with spinal cord injury

    Directory of Open Access Journals (Sweden)

    Snedecor SJ

    2013-07-01

    Full Text Available Sonya J Snedecor,1 Lavanya Sudharshan,1 Joseph C Cappelleri,2 Alesia Sadosky,3 Pooja Desai,4 Yash J Jalundhwala,5 Marc Botteman1 1Pharmerit International, Bethesda, MD, USA; 2Global Research and Development, Pfizer, Groton, CT, USA; 3Biostatistics, Pfizer, New York, NY, USA; 4College of Pharmacy, University of Texas at Austin, Austin, TX, USA; 5Pharmacy Administration, University of Illinois at Chicago, Chicago, IL, USA Background: Management of neuropathic pain (NeP associated with spinal cord injury (SCI is difficult. This report presents a systematic literature review and comparison of the efficacy and safety of pharmacologic therapies for treating SCI-associated NeP. Methods: Medline, Embase, Cochrane, and Database of Abstracts of Reviews of Effects were searched through December 2011 for randomized, blinded, and controlled clinical trials of SCI-associated NeP meeting predefined inclusion criteria. Efficacy outcomes of interest were pain reduction on the 11-point numeric rating scale (NRS or 100 mm visual analog scale and proportion of patients achieving ≥30% or ≥50% pain reduction. Discontinuations and adverse events (AEs were also assessed, for which Bayesian meta-analytic indirect comparisons were performed. Results: Of the nine studies included in the analysis, samples were <100 patients, except for one pregabalin study (n = 136. Standard errors for the NRS outcome were often not reported, precluding quantitative comparisons across treatments. Estimated 11-point NRS pain reduction relative to placebo was –1.72 for pregabalin, –1.65 for amitriptyline, –1.0 for duloxetine, –1 (median for levetiracetam, –0.27 for gabapentin, 1 (median for lamotrigine, and 2 for dronabinol. Risk ratios relative to placebo for 30% improvement were 0.71 for levetiracetam and 2.56 for pregabalin, and 0.94 and 2.91, respectively, for 50% improvement. Meta-analytic comparisons showed significantly more AEs with pregabalin and tramadol compared with

  11. Dalteparin versus vitamin K antagonists for the prevention of recurrent venous thromboembolism in patients with cancer and renal impairment: a Canadian pharmacoeconomic analysis

    Directory of Open Access Journals (Sweden)

    Dranitsaris G

    2017-01-01

    Full Text Available George Dranitsaris,1 Lesley G Shane,2 Mark Crowther,3 Guillaume Feugere,4 Seth Woodruff2 1Health Economic and Outcomes Research, Augmentium Pharma Consulting Inc, Toronto, ON, Canada; 2Pfizer Inc, New York, NY, USA; 3McMaster University, Hamilton, ON, 4Pfizer Canada, Montreal, QC, Canada Background: Patients with cancer are at increased risk of venous thromboembolism (VTE and the risk is further elevated after a primary VTE. To reduce the risk of recurrent events, extended prophylaxis with vitamin K antagonists (VKA is available for use. However, in a large randomized trial (Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer [CLOT]; Lee et al, extended duration dalteparin reduced the relative risk of recurrent VTE by 52% compared to VKA (p=0.002. A recent subgroup analysis of patients with moderate-to-severe renal impairment also revealed lower absolute VTE rates with dalteparin (3% vs. 17%; p=0.011. To measure the economic value of dalteparin as an alternative to VKA, a patient-level cost utility analysis was conducted from a Canadian perspective. Methods: Resource use data captured during the CLOT trial were extracted and linked to 2015 Canadian unit cost estimates. Health state utilities were then measured using the Time-Trade-Off technique in 24 randomly selected members of the general Canadian public to estimate the gains in quality-adjusted life years (QALYs. Results: For the entire CLOT trial population (n=676, the dalteparin group had significantly higher mean costs compared to the VKA group ($Can5,771 vs. $Can2,569; p<0.001. However, the utility assessment revealed that 21 of 24 respondents (88% selected dalteparin over VKA, with an associated gain of 0.14 (95% confidence interval [CI]: 0.10–0.18 QALYs. When the incremental cost of dalteparin was combined with the QALY gain, dalteparin had a cost of $Can23,100 (95% CI: $Can19,200

  12. Compatibility of Biosimilar Filgrastim with Cytotoxic Chemotherapy during the Treatment of Malignant Diseases (VENICE): A Prospective, Multicenter, Non-Interventional, Longitudinal Study.

    Science.gov (United States)

    Fruehauf, Stefan; Otremba, Burkhard; Stötzer, Oliver; Rudolph, Christine

    2016-11-01

    Febrile neutropenia (FN) is a serious and frequent complication of cytotoxic chemotherapy. Biosimilar filgrastim (Nivestim™, Hospira Inc, A Pfizer Company, Lake Forest, IL, USA) is a granulocyte-colony stimulating factor licensed for the treatment of neutropenia and FN induced by myelosuppressive chemotherapy. The primary goal of this VENICE study (ClinicalTrials.gov identifier, NCT01627990) was to observe the tolerability, safety and efficacy of biosimilar filgrastim in patients receiving cancer chemotherapy. This was a prospective, multicenter, non-interventional, longitudinal study. Consenting adult patients with solid tumors or hematologic malignancies for whom cytotoxic chemotherapy and treatment with biosimilar filgrastim was planned were enrolled. Among the enrolled patients (N = 386), 81% were female, with a median age (range) of 61 (22-92) years, with 39% >65 years old. Most patients (n = 338; 88%) had solid tumors and the remainder (n = 49; 13%) had hematological malignancies. The majority of the patients (64%) received biosimilar filgrastim as primary prophylaxis and 36% as secondary prophylaxis. At the follow-up visits, for the majority of patients (95.6%) there had been no change in chemotherapy dose due to FN. For two patients (0.5%) the chemotherapy was discontinued due to FN and for four patients (1.0%) the chemotherapy dose was reduced due to FN. For the majority of patients (96.9%) the chemotherapy cycle following the first biosimilar filgrastim treatment was not delayed due to FN. For 3 patients (0.8%), the chemotherapy was delayed following the first biosimilar filgrastim treatment. Less than one-third (29.8%) of the patients experienced ≥1 adverse event that was at least potentially related to biosimilar filgrastim treatment. Biosimilar filgrastim was effective and well-tolerated in both the primary and secondary prophylactic setting in patients undergoing chemotherapy for solid tumors and hematological malignancies. Clinical

  13. Predicting early transition from sub-syndromal presentations to major mental disorders.

    Science.gov (United States)

    Cross, Shane P M; Scott, Jan; Hickie, Ian B

    2017-09-01

    Transition from at-risk state to full syndromal mental disorders is underexplored for unipolar and bipolar disorders compared with psychosis. Prospective, trans-diagnostic study of rates and predictors of early transition from sub-threshold to full syndromal mental disorder. One-year outcome of 243 consenting youth aged 15-25 years with a sub-syndromal presentation of a potentially severe mental disorder. Survival analysis and odds ratio (OR) for predictors of transition identified from baseline clinical and demographic ratings. About 17% ( n =36) experienced transition to a major mental disorder. Independent of syndromal diagnosis, transition was significantly more likely in individuals who were NEET (not in education, employment or training), in females and in those with more negative psychological symptoms (e.g. social withdrawal). NEET status and negative symptoms are modifiable predictors of illness trajectory across diagnostic categories and are not specific to transition to psychosis. I.B.H. has been a Commissioner in Australia's National Mental Health Commission since 2012. He was a board member of headspace: National Youth Mental Health Foundation until January 2012. He has led a range of community-based and pharmaceutical industry-supported depression awareness and education and training programmes. He has led projects for health professionals and the community supported by governmental, community agency and pharmaceutical industry partners (Wyeth, Eli Lilly, Servier, Pfizer, AstraZeneca) for the identification and management of depression and anxiety. He has received honoraria for presentations of his own work at educational seminars supported by a number of non-government organisations and the pharmaceutical industry (including Servier, Pfizer, AstraZeneca and Eli Lilly). He is a member of the Medical Advisory Panel for Medibank Private and also a board member of Psychosis Australia Trust. He leads an investigator-initiated study of the effects of

  14. Characterizing individual painDETECT symptoms by average pain severity

    Directory of Open Access Journals (Sweden)

    Sadosky A

    2016-07-01

    Full Text Available Alesia Sadosky,1 Vijaya Koduru,2 E Jay Bienen,3 Joseph C Cappelleri4 1Pfizer Inc, New York, NY, 2Eliassen Group, New London, CT, 3Outcomes Research Consultant, New York, NY, 4Pfizer Inc, Groton, CT, USA Background: painDETECT is a screening measure for neuropathic pain. The nine-item version consists of seven sensory items (burning, tingling/prickling, light touching, sudden pain attacks/electric shock-type pain, cold/heat, numbness, and slight pressure, a pain course pattern item, and a pain radiation item. The seven-item version consists only of the sensory items. Total scores of both versions discriminate average pain-severity levels (mild, moderate, and severe, but their ability to discriminate individual item severity has not been evaluated.Methods: Data were from a cross-sectional, observational study of six neuropathic pain conditions (N=624. Average pain severity was evaluated using the Brief Pain Inventory-Short Form, with severity levels defined using established cut points for distinguishing mild, moderate, and severe pain. The Wilcoxon rank sum test was followed by ridit analysis to represent the probability that a randomly selected subject from one average pain-severity level had a more favorable outcome on the specific painDETECT item relative to a randomly selected subject from a comparator severity level.Results: A probability >50% for a better outcome (less severe pain was significantly observed for each pain symptom item. The lowest probability was 56.3% (on numbness for mild vs moderate pain and highest probability was 76.4% (on cold/heat for mild vs severe pain. The pain radiation item was significant (P<0.05 and consistent with pain symptoms, as well as with total scores for both painDETECT versions; only the pain course item did not differ.Conclusion: painDETECT differentiates severity such that the ability to discriminate average pain also distinguishes individual pain item severity in an interpretable manner. Pain

  15. Characterizing neuropathic pain profiles: enriching interpretation of painDETECT

    Directory of Open Access Journals (Sweden)

    Cappelleri JC

    2016-07-01

    Full Text Available Joseph C Cappelleri,1 Vijaya Koduru,2 E Jay Bienen,3 Alesia Sadosky4 1Pfizer Inc, Groton, CT, USA; 2Eliassen Group, New London, CT, USA; 3Outcomes Research Consultant, New York, NY, USA; 4Pfizer Inc, New York, NY, USA Purpose: To psychometrically evaluate painDETECT, a patient-reported screening questionnaire for neuropathic pain (NeP, for discriminating among sensory pain symptoms (burning, tingling/prickling, light touching, sudden pain attacks/electric shock-type pain, cold/heat, numbness, and slight pressure. Methods: The seven-item version of painDETECT provides an overall score that targets only sensory symptoms, while the nine-item version adds responses on two items to the overall score, covering pain course pattern and pain radiation. Both versions have relevance in terms of characterizing broad NeP. The nine- and seven-item versions of painDETECT were administered to subjects with confirmed NeP across six conditions identified during office visits to US community-based physicians. Responses on the sensory symptom items were dichotomized into “at least moderate” (ie, moderate, strongly, very strongly relative to the combined other responses (never, hardly noticed, slightly. Logistic regression of dichotomized variables on the total painDETECT score provided probabilities of experiencing each symptom across the range of painDETECT scores. Results: Both painDETECT versions discriminated among the symptoms with similar probabilities across the score ranges. Using these data, the probability of moderately experiencing each pain sensory item was estimated for a particular score, providing a pain profile. Additionally, the likelihood of experiencing each sensation was determined for a discrete increase in score, ie, the odds of at least a moderate sensation of burning (versus less than a moderate sensation was 1.29 for a 1-point increase, 3.52 for a 5-point increase, and 12.42 for every 10-point increase in the nine-item painDETECT score

  16. Ambulatory and home blood pressure monitoring: gaps between clinical guidelines and clinical practice in Singapore

    Directory of Open Access Journals (Sweden)

    Setia S

    2017-07-01

    Full Text Available Sajita Setia,1 Kannan Subramaniam,2 Boon Wee Teo,3 Jam Chin Tay4 1Chief Medical Office, Medical Affairs, Pfizer Pte Ltd, Singapore; 2Global Medical Affairs, Asia Pacific Region, Pfizer Australia, West Ryde, New South Wales, Australia; 3Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 4Department of General Medicine, Tan Tock Seng Hospital, Singapore Purpose: Out-of-office blood pressure (BP measurements (home blood pressure monitoring [HBPM] and ambulatory blood pressure monitoring [ABPM] provide important additional information for effective hypertension detection and management decisions. Therefore, out-of-office BP measurement is now recommended by several international guidelines. This study evaluated the practice and uptake of HBPM and ABPM among physicians from Singapore. Materials and methods: A sample of physicians from Singapore was surveyed between 8 September and 5 October 2016. Those included were in public or private practice had been practicing for ≥3 years, directly cared for patients ≥70% of the time, and treated ≥30 patients for hypertension per month. The questionnaire covered six main categories: general BP management, BP variability (BPV awareness/diagnosis, HBPM, ABPM, BPV management, and associated training needs. Results: Sixty physicians (30 general practitioners, 20 cardiologists, and 10 nephrologists were included (77% male, 85% aged 31–60 years, and mean 22-year practice. Physicians recommended HBPM and ABPM to 81% and 27% of hypertensive patients, respectively. HBPM was most often used to monitor antihypertensive therapy (88% of physicians and 97% thought that ABPM was useful for providing information on BPV. HBPM instructions often differed from current guideline recommendations in terms of frequency, number of measurements, and timing. The proportion of consultation time devoted to discussing HBPM and BPV was one-quarter or less for 73% of physicians, and

  17. TU-G-BRA-07: Characterization of Tumor Proliferation During Successive Cycles of Anti-Angiogenic Therapy Using [F-18]FLT PET/CT

    International Nuclear Information System (INIS)

    Scarpelli, M; Perlman, S; Harmon, S; Perk, T; Scully, P; Bruce, J; Liu, G; Jeraj, R

    2015-01-01

    Purpose: Studies have shown cessation of anti-angiogenic treatment during the first cycle of therapy resulted in rebound of tumor proliferation (flare). This study characterized proliferation dynamics during the first and third cycle of anti-angiogenic treatment using [F-18]FLT PET. Methods: Thirteen patients with various solid cancers were treated with Axitinib (Pfizer, Inc) at a dose of 5mg orally, twice daily, on contiguous three-week cycles with intermittent dosing (two-weeks-on/one-week-off). All patients received three FLT PET/CT scans during cycle 1 (C1): at baseline (C1D0), peak Axitinib concentration (C1D14), and the end of washout (C1D21). Ten patients received up to an additional three scans at corresponding time points during cycle 3 (C3). Lesions were identified by a nuclear medicine physician and manually contoured. Tumor burden was quantified using standard SUV metrics. Correlations between imaging metrics across C1 and C3 were calculated using the Spearman correlation. Results: At C1 peak drug concentration 11/13 patients had decreases in SUVtotal, with median decrease of 50% (change from C1D0 to C1D14). At C3 peak drug concentration 7/7 patients had decreases in SUVtotal, with median decrease of 20% (C3D0 to C3D14). Proliferative flare during C1 washout (>20% increase from C1D14 to C1D21) occurred in 9/13 patients, with median SUVtotal increase of 190%. Flare was also seen in C3 for 5/5 patients, with median SUVtotal increase of 70% (change from C3D14 to C3D21). Correlations were found between changes in imaging metrics across C1 and C3, notably the change in SUVtotal from C1D0 to C1D21 and the change in SUVtotal from C1D0 to C3D0 (ρ = 0.80). Conclusion: Measurements of SUVtotal showed that both patient response to treatment and flare were evident in both cycles of treatment. Correlation between changes in SUVtotal across C1 and C3 suggest early time points could be used to characterize patient response in later cycles. Research funded in part by

  18. Assessing the usefulness of B-mode and colour Doppler sonography, and measurements of circulating progesterone concentrations for determining ovarian responses in superovulated ewes.

    Science.gov (United States)

    Oliveira, Mef; Ribeiro, I F; Rodriguez, Mgk; Maciel, G S; Fonseca, J F; Brandão, F Z; Bartlewski, P M

    2018-06-01

    The main goal of this study was to assess the usefulness of two imaging modalities, namely the B-mode and colour Doppler sonography, and serum progesterone (P 4 ) concentrations for determining the ovarian response in superovulated ewes. Twenty-four sexually mature Santa Inês ewes underwent the superovulatory treatment consisting of eight injections of porcine FSH (total dose of 200 or 133 or 100 mg; n = 8 ewes/total dose) given at 12-hr intervals and initiated 48 hr before CIDR ® (Pfizer Inc., Auckland, New Zealand) removal. Six days after natural mating, the ovaries of all donor ewes were visualized and examined with transrectal ultrasonography and then with videolaparoscopy to identify and enumerate corpora lutea (CL) and luteinized unovulated follicles (LUFs). Jugular blood samples were collected just prior to ovarian examinations. The total number of CL (r = .78 and 0.83, p ewes. © 2018 Blackwell Verlag GmbH.

  19. Tap and Dbp5, but not Gag, are involved in DR-mediated nuclear export of unspliced Rous sarcoma virus RNA

    International Nuclear Information System (INIS)

    LeBlanc, Jason J.; Uddowla, Sabena; Abraham, Benjamin; Clatterbuck, Sarah; Beemon, Karen L.

    2007-01-01

    All retroviruses must circumvent cellular restrictions on the export of unspliced RNAs from the nucleus. While the unspliced RNA export pathways for HIV and Mason-Pfizer monkey virus are well characterized, that of Rous sarcoma virus (RSV) is not. We have previously reported that the RSV direct repeat (DR) elements are involved in the cytoplasmic accumulation of unspliced viral RNA. Here, using fluorescent in situ hybridization (FISH), we demonstrate that unspliced viral RNAs bearing a single point mutation (G8863C) in the DR exhibit a restricted cellular localization in and around the nucleus. In contrast, wild type unspliced viral RNA had a diffuse localization throughout the nucleus and cytoplasm. Since the RSV Gag protein has a transient localization in the nucleus, we examined the effect of Gag over-expression on a DR-mediated reporter construct. While Gag did not enhance DR-mediated nuclear export, the dominant-negative expression of two cellular export factors, Tap and Dbp5, inhibited expression of the same reporter construct. Furthermore, FISH studies using the dominant-negative Dbp5 demonstrated that unspliced wild type RSV RNA was retained within the nucleus. Taken together, these results further implicate the DR in nuclear RNA export through interactions with Tap and Dbp5

  20. Decreasing the Rate of Metabolic Ketone Reduction in the Discovery of a Clinical Acetyl-CoA Carboxylase Inhibitor for the Treatment of Diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Griffith, David A. [Pfizer Worldwide Research and Development, Cambridge, MA (United States); Kung, Daniel W. [Pfizer Worldwide Research and Development, Cambridge, MA (United States); Esler, William P. [Pfizer Worldwide Research and Development, Cambridge, MA (United States); Amor, Paul A. [Pfizer Worldwide Research and Development, Cambridge, MA (United States); Bagley, Scott W. [Pfizer Worldwide Research and Development, Cambridge, MA (United States); Beysen, Carine [KineMed Inc., Emeryville, CA (United States); Carvajal-Gonzalez, Santos [Pfizer Worldwide Research and Development, Cambridge, MA (United States); Doran, Shawn D. [Pfizer Worldwide Research and Development, Cambridge, MA (United States); Limberakis, Chris [Pfizer Worldwide Research and Development, Cambridge, MA (United States); Mathiowetz, Alan M. [Pfizer Worldwide Research and Development, Cambridge, MA (United States); McPherson, Kirk [Pfizer Worldwide Research and Development, Cambridge, MA (United States); Price, David A. [Pfizer Worldwide Research and Development, Cambridge, MA (United States); Ravussin, Eric [Louisiana State Univ., Baton Rouge, LA (United States); Sonnenberg, Gabriele E. [Pfizer Worldwide Research and Development, Cambridge, MA (United States); Southers, James A. [Pfizer Worldwide Research and Development, Cambridge, MA (United States); Sweet, Laurel J. [Pfizer Worldwide Research and Development, Cambridge, MA (United States); Turner, Scott M. [KineMed Inc., Emeryville, CA (United States); Vajdos, Felix F. [Pfizer Worldwide Research and Development, Cambridge, MA (United States)

    2014-12-26

    We found that Acetyl-CoA carboxylase (ACC) inhibitors offer significant potential for the treatment of type 2 diabetes mellitus (T2DM), hepatic steatosis, and cancer. However, the identification of tool compounds suitable to test the hypothesis in human trials has been challenging. An advanced series of spirocyclic ketone-containing ACC inhibitors recently reported by Pfizer were metabolized in vivo by ketone reduction, which complicated human pharmacology projections. Here, we disclose that this metabolic reduction can be greatly attenuated through introduction of steric hindrance adjacent to the ketone carbonyl. Incorporation of weakly basic functionality improved solubility and led to the identification of 9 as a clinical candidate for the treatment of T2DM. Phase I clinical studies demonstrated dose-proportional increases in exposure, single-dose inhibition of de novo lipogenesis (DNL), and changes in indirect calorimetry consistent with increased whole-body fatty acid oxidation. This demonstration of target engagement validates the use of compound 9 to evaluate the role of DNL in human disease.

  1. Sandwich wound closure reduces the risk of cerebrospinal fluid leaks in posterior fossa surgery

    Directory of Open Access Journals (Sweden)

    Verena Heymanns

    2016-07-01

    Full Text Available Posterior fossa surgery is demanding and hides a significant number of obstacles starting from the approach to the wound closure. The risk of cerebrospinal fluid (CSF leakage in posterior fossa surgery given in the literature is around 8%. The present study aims to introduce a sandwich closure of the dura in posterior fossa surgery, which reduces significantly the number of CSF leaks (3.8% in the patients treated in our department. Three hundred and ten patients treated in our hospital in the years 2009-2013 for posterior fossa pathologies were retrospectively evaluated. The dura closure method was as following: lyophilized dura put under the dura and sealed with fibrin glue and sutures, dura adapting stitches, TachoSil® (Takeda Pharma A/S, Roskilde, Denmark, Gelfoam® (Pfizer Inc., New York, NY, USA and polymethylmethacrylate (osteoclastic craniotomy. The incidence of postsurgical complications associated with the dural closure like CSF leakage, infections, bleeding is evaluated. Only 3.8% of patients developed CSF leakage and only 0.5% needed a second surgery for CSF leakage closure. Two percent had a cerebellar bleeding with no need for re-operation and 3% had a wound infection treated with antibiotics. The sandwich wound closure we are applying for posterior fossa surgery in our patients correlates with a significant reduction of CSF leaks compared to the literature.

  2. Study of neurontin: titrate to effect, profile of safety (STEPS) trial: a narrative account of a gabapentin seeding trial.

    Science.gov (United States)

    Krumholz, Samuel D; Egilman, David S; Ross, Joseph S

    2011-06-27

    Seeding trials, clinical studies conducted by pharmaceutical companies for marketing purposes, have rarely been described in detail. We examined all documents relating to the clinical trial Study of Neurontin: Titrate to Effect, Profile of Safety (STEPS) produced during the Neurontin marketing, sales practices, and product liability litigation, including company internal and external correspondence, reports, and presentations, as well as depositions elicited in legal proceedings of Harden Manufacturing vs Pfizer and Franklin vs Warner-Lambert, most which were created between 1990 and 2009. Using a systematic search strategy, we identified and reviewed all documents related to the STEPS trial in order to identify key themes related to the trial's conduct and determine the extent of marketing involvement in its planning and implementation. Documents demonstrated that STEPS was a seeding trial posing as a legitimate scientific study. Documents consistently described the trial itself, not trial results, to be a marketing tactic in the company's marketing plans. Documents demonstrated that at least 2 external sources questioned the validity of the study before execution, and that data quality during the study was often compromised. Furthermore, documents described company analyses examining the impact of participating as a STEPS investigator on rates and dosages of gabapentin prescribing, finding a positive association. None of these findings were reported in 2 published articles. The STEPS trial was a seeding trial, used to promote gabapentin and increase prescribing among investigators, and marketing was extensively involved in its planning and implementation.

  3. Due diligence in the characterization of matrix effects in a total IL-13 Singulex™ method.

    Science.gov (United States)

    Fraser, Stephanie; Soderstrom, Catherine

    2014-04-01

    After obtaining her PhD in Cellular and Molecular biology from the University of Nevada, Reno, Stephanie has spent the last 15 years in the field of bioanalysis. She has held positions in academia, biotech, contract research and large pharma where she has managed ligand binding assay (discovery to Phase IIb clinical) and flow cytometry (preclinical) laboratories as well as taken the lead on implementing new/emergent technologies. Currently Stephanie leads Pfizer's Regulated Bioanalysis Ligand Binding Assay group, focusing on early clinical biomarker support. Interleukin (IL)-13, a Th2 cytokine, drives a range of physiological responses associated with the induction of allergic airway diseases and inflammatory bowel diseases. Analysis of IL-13 as a biomarker has provided insight into its role in disease mechanisms and progression. Serum IL-13 concentrations are often too low to be measured by standard enzyme-linked immunosorbent assay techniques, necessitating the implementation of a highly sensitive assay. Previously, the validation of a Singulex™ Erenna(®) assay for the quantitation of IL-13 was reported. Herein we describe refinement of this validation; defining the impact of matrix interference on the lower limit of quantification, adding spiked matrix QC samples, and extending endogenous IL-13 stability. A fit-for-purpose validation was conducted and the assay was used to support a Phase II clinical trial.

  4. What Malaysian women believe about Viagra: a qualitative inquiry.

    Science.gov (United States)

    Low, W Y; Zulkifli, S N; Wong, Y L; Tan, H M

    2002-03-01

    This paper highlights women's perceptions of sildenafil citrate (Viagra, Pfizer). It is based on a qualitative study on perceptions of erectile dysfunction in the Malaysian multicultural society. Six focus groups were conducted, consisting of 69 women, aged between 40 and 70 years, recruited from the general public and who had given informed consent. The findings revealed that the women were aware of erectile dysfunction and Viagra. Due to their concern about the negative aspects of Viagra, the Chinese and Malay traditional methods of treatment were commonly mentioned. The women from three ethnic groups viewed the possibility of their husband starting to take Viagra with lots of suspicion, mistrust and fear. They would prefer their husband discussing with them the issue of resorting to taking Viagra. The Chinese and Indian women perceived that if a man takes Viagra, it will boost his ego and he will feel more manly. Indian women felt that a man taking Viagra is proof of his love for his wife. The Malay women felt that a man would be ashamed and have a low self-esteem if he were to resort to taking Viagra. Although Viagra is meant for the male, understanding of women's perception of it is beneficial for a couple's sexual relationship.

  5. [Effects of an additional nonsteroidal anti-inflammatory therapy with carprofen (Rimadyl Rind) in cases of severe mastitis of high yielding cows].

    Science.gov (United States)

    Krömker, Volker; Paduch, Jan-Hendrik; Abograra, Ismail; Zinke, Claudia; Friedrich, Julia

    2011-01-01

    This field study focuses on the possible effects of a combination of nonsteroidal anti-inflammatory treatment (carprofen) and a local and parenteral antibiotic on cure rates, survival rate and return to milk production of severe clinical mastitis cases. 69 cows in 3 herds (blocked by parity) with severe clinical mastitis during the first 120 d of lactation (median = 28 d) were treated with antibiotics and one-half of these cows were treated with 1.4 mg/kg bodyweight carprofen (Rimadyl Rind, Pfizer GmbH Tiergesundheit, Germany). Double milk samples for bacteriology were collected from clinically affected udder quarters before treatment and at 14 (+/- 3) and 21 (+/- 3) days after commencement of treatment for cytomicro-temperature, clinical, bacteriological, cytobacteriological cure rate and in the number of cows that were defined as treatment failures (i.e., died, re-treated, relapse). Six (22.2%) vs. seven (19.4%) cows in the carprofen and control groups failed, respectively. The milk yield was significantly higher in the carprofen-treated group compared with the control group after treatment. The present work gives first indications that treatment of cows with severe clinical mastitis with a combination of carprofen and antibiotics could result in a faster return to milk production compared to treatment with antibiotics alone. If this effect can be affiliated to the administration of carprofen alone has to be examined in further studies.

  6. The European Commission 2008 Directive Proposal on Biofuels - Comment

    Directory of Open Access Journals (Sweden)

    Florent Pelsy

    2008-09-01

    Full Text Available This article focuses on the 2008 Directive Proposal of the European Commission on biofuels. The development of biofuels as a renewable energy source has been perceived as a priority by the European Union. Indeed biofuels are approached by the EU as a new 'win-win' solution that could both reduce emission of greenhouses gases in the context of climate change and improve energy security while not affecting the European economic growth. The 2008 Directive Proposal of the Commission requires an objective of ten per cent of biofuels in the EU Transport in 2020. In order to qualify within that target biofuels shall be produced according to certain environmental criteria. This article points out the tremendous negative impacts on food security and the environment both in the developed and in the developing world of such a large-scale consumption of biofuels. It then considers that the environmental criteria required by the Directive Proposal of the Commission are not likely to be the adequate response to tackle the negative consequences of the implementation of that ten per cent target. It, thus, suggests the application of the precautionary principle as sketched out by the European Court of Justice in the case Pfizer - Alpharma to that ten per cent target and a moratorium on biofuels at the EU level.

  7. Therapeutic Efficacy and Safety of GH in Japanese Children with Down Syndrome Short Stature Accompanied by GH Deficiency.

    Science.gov (United States)

    Meguri, Kyoko; Inoue, Masaru; Narahara, Koji; Sato, Takahiro; Takata, Ami; Ohki, Nobuhiko; Ozono, Keiichi

    2013-10-01

    In this study, we investigated the effects of GH treatment in children with Down syndrome who had been diagnosed with GH deficiency (GHD). A total of 20 subjects were investigated in this study. Fourteen Down syndrome children (5 boys and 9 girls) with short stature due to GHD were treated with GH at Okayama Red Cross General Hospital, and 6 Down syndrome children (4 boys and 2 girls) with short stature due to GHD were registered in the Pfizer International Growth Database (KIGS). Height SD score (SDS) increased throughout the three-year GH treatment period. The overall mean height SDS increased from -3.5 at baseline to -2.5 after 3 yr of treatment. The mean change in height SDS during these 3 yr was 1.1. In addition, height assessment of SD score based on Down syndrome-specific growth data in the Japanese population revealed that the height SDS (Down syndrome) also increased across the 3-yr GH treatment period. The mean change in height SDS (Down syndrome) during these three years was 1.3. GH therapy was effective for Down syndrome short stature accompanied by GHD, and no new safety concerns were found in this study.

  8. Treatment of premenstrual dysphoric disorder with luteal phase dosing of sertraline.

    Science.gov (United States)

    Halbreich, Uriel; Kahn, Linda S

    2003-11-01

    Sertraline (Zoloft, Pfizer Inc.) is a selective serotonin re-uptake inhibitor (SSRI) which has been approved by the US FDA for the treatment of premenstrual dysphoric disorder (PMDD). PMDD is a severe form of premenstrual syndrome (PMS) which affects at least 5 - 8% of women of reproductive age. It is characterised by cyclic appearance at the late luteal phase of the menstrual cycle, and disappearance following the beginning of menses, with no symptoms during at least 1 week of the cycle - usually during the mid-follicular phase. Due to the cyclic luteal occurrence of PMDD, luteal phase dosing of SSRIs has been suggested and proven effective for sertraline as well as several other SSRIs. The clinical response of sertraline is reported to be within several days following initiation of treatment. Despite repeated cyclic discontinuation, no significant discontinuation adverse effects have been reported. In addition to its proven clinical efficacy, luteal-phase dosing may offer the advantages of minimising adverse effects of SSRIs while reducing the personal and economic burden of taking a prescription medication continuously for long periods and thus increasing compliance.

  9. FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer.

    Science.gov (United States)

    Beaver, Julia A; Amiri-Kordestani, Laleh; Charlab, Rosane; Chen, Wei; Palmby, Todd; Tilley, Amy; Zirkelbach, Jeanne Fourie; Yu, Jingyu; Liu, Qi; Zhao, Liang; Crich, Joyce; Chen, Xiao Hong; Hughes, Minerva; Bloomquist, Erik; Tang, Shenghui; Sridhara, Rajeshwari; Kluetz, Paul G; Kim, Geoffrey; Ibrahim, Amna; Pazdur, Richard; Cortazar, Patricia

    2015-11-01

    On February 3, 2015, the FDA granted accelerated approval to palbociclib (IBRANCE, Pfizer Inc.), an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), for use in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. The approval is based on a randomized, multicenter, open-label phase I/II trial (PALOMA-1) in 165 patients randomized to palbociclib (125 mg orally daily for 21 consecutive days, followed by 7 days off treatment) plus letrozole (2.5 mg orally daily) or letrozole alone. The phase II portion of the trial was divided into two cohorts: cohort 1 enrolled 66 biomarker-unselected patients and cohort 2 enrolled 99 biomarker-positive patients. The major efficacy outcome measure was investigator-assessed progression-free survival (PFS). A large magnitude of improvement in PFS was observed in patients receiving palbociclib plus letrozole compared with patients receiving letrozole alone (HR, 0.488; 95% confidence interval, 0.319-0.748). Multiple sensitivity analyses were supportive of clinical benefit. The most common adverse reaction in patients receiving palbociclib plus letrozole was neutropenia. This article summarizes the FDA thought process and data supporting accelerated approval based on PALOMA-1 that may be contingent upon verification and description of clinical benefit in the ongoing and fully accrued confirmatory trial PALOMA-2. ©2015 American Association for Cancer Research.

  10. Bioequivalence of fixed-dose combination Myrin®-P Forte and reference drugs in loose combination.

    Science.gov (United States)

    Wang, H F; Wang, R; O'Gorman, M; Crownover, P; Naqvi, A; Jafri, I

    2013-12-01

    Myrin®-P Forte is a fixed-dose combination (FDC) tablet containing rifampicin (RMP, 150 mg), isoniazid (INH, 75 mg), ethambutol (EMB) hydrochloride (275 mg) and pyrazinamide (PZA, 400 mg) developed for the treatment of tuberculosis (TB). This study was conducted at a single centre--the Pfizer Clinical Research Unit in Singapore. To demonstrate the bioequivalence of each drug component of the Myrin-P Forte FDC and the individual product in loose combination. In a randomized, open-label, single-dose, two-way, crossover study, subjects received single doses of Myrin-P Forte or four individual products under fasting conditions in a crossover fashion with at least 7 days washout between doses. The primary measures for comparison were peak plasma concentration (C(max)) and the area under plasma concentration-time curve (AUC). Of 36 subjects enrolled, 35 completed the study. The adjusted geometric mean ratios and 90% confidence intervals for C(max) and AUC values were completely contained within bioequivalence limits (80%, 125%) for all four drugs in both formulations. Both treatments were generally well tolerated in the study. The Myrin-P Forte FDC tablet formulation is bioequivalent to the four single-drug references for RMP, INH, EMB hydrochloride and PZA at equivalent doses.

  11. Bioequivalence of fixed-dose combination RIN®-150 to each reference drug in loose combination.

    Science.gov (United States)

    Wang, H F; Wang, R; O'Gorman, M; Crownover, P; Damle, B

    2015-03-01

    RIN(®)-150 is a fixed-dose combination (FDC) tablet containing rifampicin (RMP, 150 mg) and isoniazid (INH, 75 mg) developed for the treatment of tuberculosis. This study was conducted at a single center: the Pfizer Clinical Research Unit in Singapore. To demonstrate bioequivalence of each drug component between RIN-150 and individual products in a loose combination. This was a randomized, open-label, single-dose, two-way crossover study. Subjects received single doses of RIN-150 or two individual reference products under fasting conditions in a crossover fashion, with at least 7 days washout between doses. The primary measures for comparison were peak plasma concentration (Cmax) and the area under plasma concentration-time curve (AUC). Of 28 subjects enrolled, 26 completed the study. The adjusted geometric mean ratios of Cmax and AUClast between the FDC and single-drug references and 90% confidence intervals were respectively 91.63% (90%CI 83.13-101.01) and 95.45% (90%CI 92.07-98.94) for RMP, and 107.58% (90%CI 96.07-120.47) and 103.45% (90%CI 99.33-107.75) for INH. Both formulations were generally well tolerated in this study. The RIN-150 FDC tablet formulation is bioequivalent to the two single-drug references for RMP and INH at equivalent doses.

  12. A data-driven approach to quality risk management.

    Science.gov (United States)

    Alemayehu, Demissie; Alvir, Jose; Levenstein, Marcia; Nickerson, David

    2013-10-01

    An effective clinical trial strategy to ensure patient safety as well as trial quality and efficiency involves an integrated approach, including prospective identification of risk factors, mitigation of the risks through proper study design and execution, and assessment of quality metrics in real-time. Such an integrated quality management plan may also be enhanced by using data-driven techniques to identify risk factors that are most relevant in predicting quality issues associated with a trial. In this paper, we illustrate such an approach using data collected from actual clinical trials. Several statistical methods were employed, including the Wilcoxon rank-sum test and logistic regression, to identify the presence of association between risk factors and the occurrence of quality issues, applied to data on quality of clinical trials sponsored by Pfizer. ONLY A SUBSET OF THE RISK FACTORS HAD A SIGNIFICANT ASSOCIATION WITH QUALITY ISSUES, AND INCLUDED: Whether study used Placebo, whether an agent was a biologic, unusual packaging label, complex dosing, and over 25 planned procedures. Proper implementation of the strategy can help to optimize resource utilization without compromising trial integrity and patient safety.

  13. A data-driven approach to quality risk management

    Directory of Open Access Journals (Sweden)

    Demissie Alemayehu

    2013-01-01

    Full Text Available Aim: An effective clinical trial strategy to ensure patient safety as well as trial quality and efficiency involves an integrated approach, including prospective identification of risk factors, mitigation of the risks through proper study design and execution, and assessment of quality metrics in real-time. Such an integrated quality management plan may also be enhanced by using data-driven techniques to identify risk factors that are most relevant in predicting quality issues associated with a trial. In this paper, we illustrate such an approach using data collected from actual clinical trials. Materials and Methods: Several statistical methods were employed, including the Wilcoxon rank-sum test and logistic regression, to identify the presence of association between risk factors and the occurrence of quality issues, applied to data on quality of clinical trials sponsored by Pfizer. Results: Only a subset of the risk factors had a significant association with quality issues, and included: Whether study used Placebo, whether an agent was a biologic, unusual packaging label, complex dosing, and over 25 planned procedures. Conclusion: Proper implementation of the strategy can help to optimize resource utilization without compromising trial integrity and patient safety.

  14. Combined Treatment with Amlodipine and Atorvastatin Calcium Reduces Circulating Levels of Intercellular Adhesion Molecule-1 and Tumor Necrosis Factor-α in Hypertensive Patients with Prediabetes.

    Science.gov (United States)

    Huang, Zhouqing; Chen, Chen; Li, Sheng; Kong, Fanqi; Shan, Peiren; Huang, Weijian

    2016-01-01

    To assess the effect of amlodipine and atorvastatin on intercellular adhesion molecule (ICAM)-1 and tumor necrosis factor (TNF)-α expression, as endothelial function and inflammation indicators, respectively, in hypertensive patients with and without prediabetes. Forty-five consecutive patients with hypertension, diagnosed according to JNC7, were divided into two groups based on the presence (HD group, n = 23) or absence (H group, n = 22) of prediabetes, diagnosed according to 2010 ADA criteria, including impaired glucose tolerance (IGT) and fasting glucose tests. All patients simultaneously underwent 12-week treatment with daily single-pill amlodipine besylate/atorvastatin calcium combination (5/10 mg; Hisun-Pfizer Pharmaceuticals Co. Ltd). Serum isolated before and after treatment from overnight fasting blood samples was analyzed by ELISA. In the HD and H groups after vs. before 12-week amlodipine/atorvastatin treatment, there were significantly (all P atorvastatin improved endothelial function and inflammation, as reflected by lower circulating levels of ICAM-1 and TNF-α, more prominently in hypertensives with than without prediabetes. Starting statin treatment before overt diabetes in hypertensives might thus improve cardiovascular outcomes.

  15. Fundamental studies of computed tomography, 9

    International Nuclear Information System (INIS)

    Mano, Isamu; Takai, Michikatsu; Sugie, Yoshio; Kaneko, Masao

    1981-01-01

    A performance evaluation of 9 CT scanners (a Pfizer AS and E 0450, a Delta-2020, a Somatom 2, a Toshiba TCT-60A, a Hitachi CT-W3, and 4 GE CT/T 8800 scanners) was carried out using the standardized phantom, the details of which were presented in the first report of the Japanese Committee on CT Performance Evaluation. The scanning conditions used were followed by means of the usual head mode of each scanner. This time, the clinically important parameters, such as the high- and low-contrast resolving power, the size, and the location effect, were reported. As a result, it was found that all the scanners tested this time were obviously superior in image quality to the first- and second-generation scanners, the performance of which we had already reported on. Since motion artifacts are thought to be far fewer in the former scanners, their clinical image quality would be much better than the latter ones. The resolving powers of third-generation scanners seemed slightly better than these of the fourth-generation scanners; meanwhile, the artifact's appearance was recognized to be better in the third-generation scanners. According to the data on the four scanners manufactured by the G. E. Co., Ltd., their performances were at almost the same level. (author)

  16. Commentary: Impact of meningococcal group B OMV vaccines, beyond their brief.

    Science.gov (United States)

    Petousis-Harris, Helen

    2017-10-19

    Meningococcal group B outer membrane vesicle vaccines have been used widely in Cuba, New Zealand, and Brazil. They are immunogenic and initially assessed largely by their ability to induce serum bactericidal activity. Measures of efficacy indicate good protection against homologous strains in older children and adults. Effectiveness appears broader than predicted by immunogenicity and efficacy studies. The recent discovery that meningococcal group B OMVs may protect against the related Neisseria species N.gonorrhoeae suggests more to these interesting antigen collections than meets the eye. Currently there are two OMV-containing group B vaccines available, the new recombinant protein-based Bexsero® developed by Novartis and VA-MENGOC-BC® developed by the Finlay institute in Cuba. Also, a third group B vaccine based on two recombinant factor H binding proteins (Trumenba®, Pfizer), has recently been licenced but it does not include OMV. This commentary explores the population impact that group B OMV vaccines have had on meningococcal and gonorrhoea diseases. Given the heterologous effect against diverse strains of the meningococcus observed in older children and adults, and recent evidence to suggest moderate protection against gonorrhoea, there may be a role for these vaccines in programmes targeting adolescents and groups high at risk for both meningococcal disease and gonorrhoea.

  17. Interlaboratory assessment of mitotic index by flow cytometry confirms superior reproducibility relative to microscopic scoring.

    Science.gov (United States)

    Roberts, D J; Spellman, R A; Sanok, K; Chen, H; Chan, M; Yurt, P; Thakur, A K; DeVito, G L; Murli, H; Stankowski, L F

    2012-05-01

    A flow cytometric procedure for determining mitotic index (MI) as part of the metaphase chromosome aberrations assay, developed and utilized routinely at Pfizer as part of their standard assay design, has been adopted successfully by Covance laboratories. This method, using antibodies against phosphorylated histone tails (H3PS10) and nucleic acid stain, has been evaluated by the two independent test sites and compared to manual scoring. Primary human lymphocytes were treated with cyclophosphamide, mitomycin C, benzo(a)pyrene, and etoposide at concentrations inducing dose-dependent cytotoxicity. Deming regression analysis indicates that the results generated via flow cytometry (FCM) were more consistent between sites than those generated via microscopy. Further analysis using the Bland-Altman modification of the Tukey mean difference method supports this finding, as the standard deviations (SDs) of differences in MI generated by FCM were less than half of those generated manually. Decreases in scoring variability owing to the objective nature of FCM, and the greater number of cells analyzed, make FCM a superior method for MI determination. In addition, the FCM method has proven to be transferable and easily integrated into standard genetic toxicology laboratory operations. Copyright © 2012 Wiley Periodicals, Inc.

  18. The role of user representation and Arthritis and Rheumatism International.

    Science.gov (United States)

    Johnstone, Robert

    2003-08-01

    Arthritis and Rheumatism International (ARi), founded in 1988, is an association of national lay organizations comprising mainly people whose lives are affected by arthritis and rheumatism. ARi's charter defines the organization's aims, including to raise awareness of the needs of people with arthritis/rheumatism, to improve the quality of their lives through education and self-management programs, and to support research into causes, management, prevention, and cure of arthritis. With the aid of a grant from the Pfizer Foundation in 2002, ARi has been able to further develop into a strong organization throughout the world, with a membership of 22 countries. Successful intitiatives include the People with Arthritis and Rheumatism in Europe Manifesto, which has served as a very effective focus for developing action plans, opening dialogues, building partnerships with other organizations, lobbying governments, and gaining media attention throughout Europe. The manifesto (website: www.PAREmanifesto.org) was developed by ARi working in conjunction with The International Organisation of Youth with Rheumatism and the EULAR Social League. These are examples of initiatives that ARi aims to promote on a global scale in the next few years.

  19. Performance on a CT Scanner. Application for the dose correction in the presence of heterogeneities, experimental study using high energy photon beams

    International Nuclear Information System (INIS)

    Hanna, Therese.

    1979-01-01

    The purpose of this work is the physical analysis of a second generation C T scanner: the A C T A Scanner 0200 FS (PFIZER) used at the 'Institut Gustave Roussy, Villejuif' and its application in radiotherapy. The first part of the study specifically concerns the physical performance of the C T Scanner, and, the evaluation of the doses, delivered to patients during tomodensitometric examinations. The second part envisages the possibilities of the application of C T scanning in radiotherapy. A particular study is established for the utilization of the physical characteristics, furnished by the C T Scanner, concerning different organs, in dose calculations, in the presence of heterogeneities. An experimental study using high energy photon beams more particularly 25 MV X ray beams produced by a linear accelerator (type Sagittaire) has been realized with materials, simulating different human tissues. Consequently, the validity of different correction methods proposed in the literature has been tested for the soft tissues and bone as for the lungs. Modifications are suggested to allow the use of these methods for the photons of very high energy [fr

  20. Donated chemical probes for open science.

    Science.gov (United States)

    Müller, Susanne; Ackloo, Suzanne; Arrowsmith, Cheryl H; Bauser, Marcus; Baryza, Jeremy L; Blagg, Julian; Böttcher, Jark; Bountra, Chas; Brown, Peter J; Bunnage, Mark E; Carter, Adrian J; Damerell, David; Dötsch, Volker; Drewry, David H; Edwards, Aled M; Edwards, James; Elkins, Jon M; Fischer, Christian; Frye, Stephen V; Gollner, Andreas; Grimshaw, Charles E; IJzerman, Adriaan; Hanke, Thomas; Hartung, Ingo V; Hitchcock, Steve; Howe, Trevor; Hughes, Terry V; Laufer, Stefan; Li, Volkhart Mj; Liras, Spiros; Marsden, Brian D; Matsui, Hisanori; Mathias, John; O'Hagan, Ronan C; Owen, Dafydd R; Pande, Vineet; Rauh, Daniel; Rosenberg, Saul H; Roth, Bryan L; Schneider, Natalie S; Scholten, Cora; Singh Saikatendu, Kumar; Simeonov, Anton; Takizawa, Masayuki; Tse, Chris; Thompson, Paul R; Treiber, Daniel K; Viana, Amélia Yi; Wells, Carrow I; Willson, Timothy M; Zuercher, William J; Knapp, Stefan; Mueller-Fahrnow, Anke

    2018-04-20

    Potent, selective and broadly characterized small molecule modulators of protein function (chemical probes) are powerful research reagents. The pharmaceutical industry has generated many high-quality chemical probes and several of these have been made available to academia. However, probe-associated data and control compounds, such as inactive structurally related molecules and their associated data, are generally not accessible. The lack of data and guidance makes it difficult for researchers to decide which chemical tools to choose. Several pharmaceutical companies (AbbVie, Bayer, Boehringer Ingelheim, Janssen, MSD, Pfizer, and Takeda) have therefore entered into a pre-competitive collaboration to make available a large number of innovative high-quality probes, including all probe-associated data, control compounds and recommendations on use (https://openscienceprobes.sgc-frankfurt.de">https://openscienceprobes.sgc-frankfurt.dehttps://openscienceprobes.sgc-frankfurt.de/">/). Here we describe the chemical tools and target-related knowledge that have been made available, and encourage others to join the project. © 2018, Müller et al.

  1. Selective Inhibitors of Protozoan Protein N-myristoyltransferases as Starting Points for Tropical Disease Medicinal Chemistry Programs

    Science.gov (United States)

    Bell, Andrew S.; Mills, James E.; Williams, Gareth P.; Brannigan, James A.; Wilkinson, Anthony J.; Parkinson, Tanya; Leatherbarrow, Robin J.; Tate, Edward W.; Holder, Anthony A.; Smith, Deborah F.

    2012-01-01

    Inhibition of N-myristoyltransferase has been validated pre-clinically as a target for the treatment of fungal and trypanosome infections, using species-specific inhibitors. In order to identify inhibitors of protozoan NMTs, we chose to screen a diverse subset of the Pfizer corporate collection against Plasmodium falciparum and Leishmania donovani NMTs. Primary screening hits against either enzyme were tested for selectivity over both human NMT isoforms (Hs1 and Hs2) and for broad-spectrum anti-protozoan activity against the NMT from Trypanosoma brucei. Analysis of the screening results has shown that structure-activity relationships (SAR) for Leishmania NMT are divergent from all other NMTs tested, a finding not predicted by sequence similarity calculations, resulting in the identification of four novel series of Leishmania-selective NMT inhibitors. We found a strong overlap between the SARs for Plasmodium NMT and both human NMTs, suggesting that achieving an appropriate selectivity profile will be more challenging. However, we did discover two novel series with selectivity for Plasmodium NMT over the other NMT orthologues in this study, and an additional two structurally distinct series with selectivity over Leishmania NMT. We believe that release of results from this study into the public domain will accelerate the discovery of NMT inhibitors to treat malaria and leishmaniasis. Our screening initiative is another example of how a tripartite partnership involving pharmaceutical industries, academic institutions and governmental/non-governmental organisations such as Medical Research Council and Wellcome Trust can stimulate research for neglected diseases. PMID:22545171

  2. The conserved dileucine- and tyrosine-based motifs in MLV and MPMV envelope glycoproteins are both important to regulate a common Env intracellular trafficking

    Directory of Open Access Journals (Sweden)

    Lopez-Vergès Sandra

    2006-09-01

    Full Text Available Abstract Background Retrovirus particles emerge from the assembly of two structural protein components, Gag that is translated as a soluble protein in the cytoplasm of the host cells, and Env, a type I transmembrane protein. Because both components are translated in different intracellular compartments, elucidating the mechanisms of retrovirus assembly thus requires the study of their intracellular trafficking. Results We used a CD25 (Tac chimera-based approach to study the trafficking of Moloney murine leukemia virus and Mason-Pfizer monkey virus Env proteins. We found that the cytoplasmic tails (CTs of both Env conserved two major signals that control a complex intracellular trafficking. A dileucine-based motif controls the sorting of the chimeras from the trans-Golgi network (TGN toward endosomal compartments. Env proteins then follow a retrograde transport to the TGN due to the action of a tyrosine-based motif. Mutation of either motif induces the mis-localization of the chimeric proteins and both motifs are found to mediate interactions of the viral CTs with clathrin adaptors. Conclusion This data reveals the unexpected complexity of the intracellular trafficking of retrovirus Env proteins that cycle between the TGN and endosomes. Given that Gag proteins hijack endosomal host proteins, our work suggests that the endosomal pathway may be used by retroviruses to ensure proper encountering of viral structural Gag and Env proteins in cells, an essential step of virus assembly.

  3. Real-World Economic Outcomes During Time on Treatment Among Patients Who Initiated Sunitinib or Pazopanib as First Targeted Therapy for Advanced Renal Cell Carcinoma: A Retrospective Analysis of Medicare Claims Data.

    Science.gov (United States)

    Vogelzang, Nicholas J; Pal, Sumanta K; Ghate, Sameer R; Li, Nanxin; Swallow, Elyse; Peeples, Miranda; Zichlin, Miriam L; Meiselbach, Mark K; Perez, Jose Ricardo; Agarwal, Neeraj

    2018-06-01

    outpatient visits and costs but lower mean total all-cause pharmacy costs, than the sunitinib cohort (all P < 0.05). After matching, the pazopanib and sunitinib cohorts had similar characteristics (mean age 75 years, 58% male, and Charlson Comorbidity Index score of 9.2 in both cohorts) and median TOT (4.8 and 4.1 months, respectively). Among the 522 matched pairs, pazopanib was associated with significantly lower total all-cause health care costs ($8,527 vs. $10,924, respectively [mean difference = $2,397]); total medical costs ($3,991 vs. $5,881, respectively, [$1,890]); and inpatient costs ($2,040 vs. $3,731, respectively, [$1,692]; all P < 0.01) compared with sunitinib. Patients receiving pazopanib had significantly fewer inpatient admissions (0.179 vs. 0.289, respectively) and days (1.063 vs. 1.904, respectively; both P < 0.01) than patients receiving sunitinib. Mean treatment compliance was lower for the pazopanib versus sunitinib cohort (0.91 vs. 0.94, respectively; P < 0.01). In this retrospective analysis of Medicare patients with aRCC from a TOT perspective, first targeted therapy with pazopanib was associated with significantly lower all-cause health care costs and HRU, but lower compliance, compared with sunitinib. Funding for this research was provided by Novartis Pharmaceuticals. The sponsor was involved in all stages of the study's conduct and reporting. Vogelzang has been a consultant for Novartis, Amgen, Celgene, Medivation, Eisai, Exelixis, and Roche; has spoken at Novartis, Astellas, Johnson and Johnson, Pfizer, Dendreon, Bayer/Algeta, GSK, and Veridex/Janssen; and has received research support from Novartis, Bayer, Exelixis, Progenics, Bavarian Nordic, and Viamet. Pal has been a consultant for Novartis, Pfizer, Aveo, Dendreon, and Myriad and has spoken at Novartis, Pfizer and Medivation. Agarwal has been a consultant or advisor for Novartis, Pfizer, Exelixis, Cerulean Pharma, Medivation, Eisai, and Argos Therapeutics. Swallow, Peeples, Zichlin, and

  4. Hardness, function, emotional well-being, satisfaction and the overall sexual experience in men using 100-mg fixed-dose or flexible-dose sildenafil citrate

    Science.gov (United States)

    Ströberg, P; Kaminetsky, J C; Park, N C; Goldfischer, E R; Creanga, D L; Stecher, V J

    2010-01-01

    The prescribing information for sildenafil citrate (VIAGRA, Pfizer, New York, NY, USA) recommends flexible dosing (50 mg initially, adjusted to 100 or 25 mg based on effectiveness and tolerability) in most men with erectile dysfunction (ED). In many men, however, 100 mg may be the most appropriate initial dose because it would reduce the need for titration and could prevent discouragement and treatment abandonment should 50 mg be insufficient. Results of two previously published double-blind, placebo-controlled sildenafil trials of similar design except for a fixed-dose vs flexible-dose regimen were analyzed. Relative to the flexible-dose, approximately one-third more men were satisfied with an initial and fixed dose of 100 mg. In addition, tolerability was similar, and improvements from baseline in outcomes on validated, ED-specific, patient-reported questionnaires were either similar (erectile function and the percentage of completely hard and fully rigid erections) or greater (emotional well-being and the overall sexual experience). The similarity in outcomes is not surprising given that almost 90% of the men in the flexible-dose trial titrated to 100 mg after 2 weeks. These data suggest prescription of an initial dose of 100 mg for men with ED, except in those for whom it is inappropriate. PMID:20596083

  5. The effects of sildenafil citrate (Viagra) on uterine blood flow and well being in the intrauterine growth-restricted fetus.

    Science.gov (United States)

    Miller, Suzanne L; Loose, Jan M; Jenkin, Graham; Wallace, Euan M

    2009-01-01

    This study examined whether the type-5 phosphodiesterase inhibitor sildenafil citrate (Viagra; Pfizer, New York, NY) could increase uterine blood flow in intrauterine growth restriction (IUGR), thereby improving fetal oxygenation and well being. In fetal sheep, we induced IUGR at 105-110 days (0.7 gestation) using single umbilical artery ligation (SUAL). In SUAL and control animals, we measured uterine blood flow (UBF) and blood gases before and after sildenafil administration. SUAL fetuses were hypoxemic compared with controls. Following sildenafil, UBF was significantly decreased in both SUAL and control ewes for approximately 40 minutes. In response to sildenafil, pO(2) was decreased in SUAL and control fetuses and both groups displayed significant hypotension and tachycardia. At postmortem SUAL fetal body weight was significantly reduced by 23% compared with controls. Sildenafil does not improve UBF or fetal well being in SUAL-induced IUGR pregnancies and should be used with caution in IUGR and healthy pregnancies because of its detrimental effects on uteroplacental perfusion and on the fetus.

  6. Solid-state characterization and impurities determination of fluconazol generic products marketed in Morocco

    Science.gov (United States)

    Bourichi, Houda; Brik, Youness; Hubert, Philipe; Cherrah, Yahia; Bouklouze, Abdelaziz

    2012-01-01

    In this paper, we report the results of quality control based in physicochemical characterization and impurities determination of three samples of fluconazole drug substances marketed in Morocco. These samples were supplied by different pharmaceuticals companies. The sample A, as the discovered product, was supplied by Pfizer, while samples B and C (generics), were manufactured by two different Indian industries. Solid-state characterization of the three samples was realized with different physicochemical methods as: X-ray powder diffraction, Fourier-transformation infrared spectroscopy, differential scanning calorimetry. High performance liquid chromatography was used to quantify the impurities in the different samples. The results from the physicochemical methods cited above, showed difference in polymorph structure of the three drug substances. Sample A consisted in pure polymorph III, sample B consisted in pure polymorph II, sample C consisted in a mixture of fluconazole Form III, form II and the monohydrate. This result was confirmed by differential scanning calorimetry. Also it was demonstrated that solvents used during the re-crystallization step were among the origins of these differences in the structure form. On the other hand, the result of the stability study under humidity and temperature showed that fluconazole polymorphic transformation could be owed to the no compliance with the conditions of storage. The HPLC analysis of these compounds showed the presence of specific impurities for each polymorphic form, and a possible relationship could be exist between impurities and crystalline form of fluconazole. PMID:29403776

  7. Tolerogenic Dendritic Cells Generated with Tofacitinib Ameliorate Experimental Autoimmune Encephalomyelitis through Modulation of Th17/Treg Balance

    Directory of Open Access Journals (Sweden)

    Yan Zhou

    2016-01-01

    Full Text Available It is well known that dendritic cells (DCs play a pivotal role in triggering self-specific responses. Conversely, tolerogenic DCs (tolDCs, a specialized subset, induce tolerance and negatively regulate autoreactive responses. Tofacitinib, a Janus kinase inhibitor developed by Pfizer for treatment of rheumatoid arthritis, is probable to be a promising candidate for inducing tolDCs. The aims of this study were to evaluate the effectiveness of tolDCs induced by tofacitinib in a myelin oligodendrocyte glycoprotein- (MOG- specific experimental autoimmune encephalomyelitis (EAE model and to investigate their effects on Th17/Treg balance in the animal model of multiple sclerosis (MS. Our results revealed that tofacitinib-treated DCs maintained a steady semimature phenotype with a low level of proinflammatory cytokines and costimulatory molecules. DCs treated by tofacitinib also induced antigen-specific T cells hyporesponsiveness in a concentration-dependent manner. Upon intravenous injection into EAE mice, MOG pulsed tolDCs significantly dampened disease activity, and adoptive cell therapy (ACT disturbed Th17/Treg balance with a remarkable decrease of Th1/Th17 cells and an increase in regulatory T cells (Tregs. Overall, DCs modified by tofacitinib exhibited a typical tolerogenic phenotype, and the antigen-specific tolDCs may represent a new avenue of research for the development of future clinical treatments for MS.

  8. The endogenous langur type D retrovirus PO-1-Lu and its exogenous counterparts in macaque and langur monkeys

    International Nuclear Information System (INIS)

    Sommerfelt, Maja A.; Harkestad, Nina; Hunter, Eric

    2003-01-01

    PO-1-Lu, the endogenous type D retrovirus of langurs (Trachypithecus obscurus) has previously been considered a progenitor to the prototype type D retrovirus, Mason Pfizer monkey virus (M-PMV/SRV-3), that became established in macaque monkeys (Macaca spp.) following a zoonosis. This study reevaluates this hypothesis to include other exogenous SRVs. New sequence information from the gp70(SU)-encoding region of PO-1-Lu shows striking similarity to the newly identified exogenous langur retrovirus, SRV-6, recently isolated from the Hanuman Langur (Semnopithecus entellus). An unrooted, bootstrapped neighbor-joining tree derived from env gene nucleotide sequences shows PO-1-Lu and SRV-6 appear more closely related genetically to SRV-2 than SRV-1 or SRV-3 (M-PMV). This is also reflected in our observations that the M-PMV envelope glycoprotein precursor gPr86 Env and gp70(SU) were antigenically distinct from PO-1-Lu, although the gp22(TM) glycoproteins were antigenically cross-reactive. The potential that SRV-6 represents an exogenous form of PO-1-Lu that has arisen following a recent zoonosis is discussed

  9. Macro-economic factors influencing the architectural business model shift in the pharmaceutical industry.

    Science.gov (United States)

    Dierks, Raphaela Marie Louisa; Bruyère, Olivier; Reginster, Jean-Yves; Richy, Florent-Frederic

    2016-10-01

    Technological innovations, new regulations, increasing costs of drug productions and new demands are only few key drivers of a projected alternation in the pharmaceutical industry. The purpose of this review is to understand the macro economic factors responsible for the business model revolution to possess a competitive advantage over market players. Areas covered: Existing literature on macro-economic factors changing the pharmaceutical landscape has been reviewed to present a clear image of the current market environment. Expert commentary: Literature shows that pharmaceutical companies are facing an architectural alteration, however the evidence on the rationale driving the transformation is outstanding. Merger & Acquisitions (M&A) deals and collaborations are headlining the papers. Q1 2016 did show a major slowdown in M&A deals by volume since 2013 (with deal cancellations of Pfizer and Allergan, or the downfall of Valeant), but pharmaceutical analysts remain confident that this shortfall was a consequence of the equity market volatility. It seems likely that the shift to an M&A model will become apparent during the remainder of 2016, with deal announcements of Abbott Laboratories, AbbVie and Sanofi worth USD 45billion showing the appetite of big pharma companies to shift from the fully vertical integrated business model to more horizontal business models.

  10. Evolving landscape of human epidermal growth factor receptor 2-positive breast cancer treatment and the future of biosimilars.

    Science.gov (United States)

    Jackisch, Christian; Lammers, Philip; Jacobs, Ira

    2017-04-01

    Human epidermal growth factor receptor 2-positive (HER2+) breast cancer comprises approximately 15%-20% of all breast cancers and is associated with a poor prognosis. The introduction of anti-HER2 therapy has significantly improved clinical outcomes for patients with HER2+ breast cancer, and multiple HER2-directed agents (ie, trastuzumab, pertuzumab, lapatinib, and ado-trastuzumab emtansine [T-DM1]) are approved for clinical use in various settings. The treatment landscape for patients with HER2+ breast cancer is continuing to evolve. While novel agents and therapeutic strategies are emerging, biologic therapies, particularly trastuzumab, are likely to remain a mainstay of treatment. However, access issues create barriers to the use of biologics, and there is evidence for underuse of trastuzumab worldwide. A biosimilar is a biologic product that is highly similar to a licensed biologic in terms of product safety and effectiveness. Biosimilars of trastuzumab are in development and may soon become available. The introduction of biosimilars may improve access to anti-HER2 therapies by providing additional treatment options and lower-cost alternatives. Because HER2-targeted drugs may be administered for extended periods of time and in combination with other systemic therapies, biosimilars have the potential to result in significant savings for healthcare systems. Herein we review current and emerging treatment options for, and discuss the possible role of biosimilars in, treating patients with HER2+ breast cancer. Copyright © 2017 Authors, Pfizer Inc. Published by Elsevier Ltd.. All rights reserved.

  11. Innovators, deep fermentation and antibiotics: promoting applied science before and after the Second World War.

    Science.gov (United States)

    Bud, Robert

    2011-01-01

    The historiography of penicillin has tended to overlook the importance of developing and disseminating know-how in fermentation technology. A focus on this directs attention to work before the war of a network in the US and Europe concerned with the production of organic acids, particularly gluconic and citric acids. At the heart of this network was the German-Czech Konrad Bernhauer. Other members of the network were a group of chemists at the US Department of Agriculture who first recognized the production possibilities of penicillin. The Pfizer Corporation, which had recruited a leading Department of Agriculture scientist at the end of the First World War, was also an important centre of development as well as of production. However, in wartime Bernhauer was an active member of the SS and his work was not commemorated after his death in 1975. After the war new processes of fermentation were disseminated by penicillin pioneers such as Jackson Foster and Ernst Chain. Because of its commercial context his work was not well known. The conclusion of this paper is that the commercial context, on the one hand, and the Nazi associations of Bernhauer, on the other, have submerged the significance of know-how development in the history of penicillin.

  12. Review of the Interaction Between Body Composition and Clinical Outcomes in Metastatic Renal Cell Cancer Treated With Targeted Therapies

    Directory of Open Access Journals (Sweden)

    Steven M Yip

    2016-03-01

    Full Text Available Treatment of metastatic renal cell cancer (mRCC currently focuses on inhibition of the vascular endothelial growth factor pathway and the mammalian target of rapamycin (mTOR pathway. Obesity confers a higher risk of RCC. However, the influence of obesity on clinical outcomes in mRCC in the era of targeted therapy is less clear. This review focuses on the impact of body composition on targeted therapy outcomes in mRCC. The International Metastatic Renal Cell Carcinoma Database Consortium database has the largest series of patients evaluating the impact of body mass index (BMI on outcomes in mRCC patients treated with targeted therapy. Overall survival was significantly improved in overweight patients (BMI ≥ 25 kg/m2, and this observation was externally validated in patients who participated in Pfizer trials. In contrast, sarcopenia is consistently associated with increased toxicity to inhibitors of angiogenesis and mTOR. Strengthening patients with mRCC and sarcopenia, through a structured exercise program and dietary intervention, may improve outcomes in mRCC treated with targeted therapies. At the same time, the paradox of obesity being a risk factor for RCC while offering a better overall survival in response to targeted therapy needs to be further evaluated.

  13. Associations of centrally acting ACE inhibitors with cognitive decline and survival in Alzheimer's disease.

    Science.gov (United States)

    Fazal, Karim; Perera, Gayan; Khondoker, Mizanur; Howard, Robert; Stewart, Robert

    2017-07-01

    Cognitive improvement has been reported in patients receiving centrally acting angiotensin-converting enzyme inhibitors (C-ACEIs). To compare cognitive decline and survival after diagnosis of Alzheimer's disease between people receiving C-ACEIs, non-centrally acting angiotensin-converting enzyme inhibitors (NC-ACEIs), and neither. Routine Mini-Mental State Examination (MMSE) scores were extracted in 5260 patients receiving acetylcholinesterase inhibitors and analysed against C-/NC-ACEI exposure at the time of Alzheimer's disease diagnosis. In the 9 months after Alzheimer's disease diagnosis, MMSE scores significantly increased by 0.72 and 0.19 points per year in patients on C-ACEIs and neither respectively, but deteriorated by 0.61 points per year in those on NC-ACEIs. There were no significant group differences in score trajectories from 9 to 36 months and no differences in survival. In people with Alzheimer's disease receiving acetylcholinesterase inhibitors, those also taking C-ACEIs had stronger initial improvement in cognitive function, but there was no evidence of longer-lasting influence on dementia progression. R.S. has received research funding from Pfizer, Lundbeck, Roche, Janssen and GlaxoSmithKline. © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

  14. Design of a multi-purpose fragment screening library using molecular complexity and orthogonal diversity metrics

    Science.gov (United States)

    Lau, Wan F.; Withka, Jane M.; Hepworth, David; Magee, Thomas V.; Du, Yuhua J.; Bakken, Gregory A.; Miller, Michael D.; Hendsch, Zachary S.; Thanabal, Venkataraman; Kolodziej, Steve A.; Xing, Li; Hu, Qiyue; Narasimhan, Lakshmi S.; Love, Robert; Charlton, Maura E.; Hughes, Samantha; van Hoorn, Willem P.; Mills, James E.

    2011-07-01

    Fragment Based Drug Discovery (FBDD) continues to advance as an efficient and alternative screening paradigm for the identification and optimization of novel chemical matter. To enable FBDD across a wide range of pharmaceutical targets, a fragment screening library is required to be chemically diverse and synthetically expandable to enable critical decision making for chemical follow-up and assessing new target druggability. In this manuscript, the Pfizer fragment library design strategy which utilized multiple and orthogonal metrics to incorporate structure, pharmacophore and pharmacological space diversity is described. Appropriate measures of molecular complexity were also employed to maximize the probability of detection of fragment hits using a variety of biophysical and biochemical screening methods. In addition, structural integrity, purity, solubility, fragment and analog availability as well as cost were important considerations in the selection process. Preliminary analysis of primary screening results for 13 targets using NMR Saturation Transfer Difference (STD) indicates the identification of uM-mM hits and the uniqueness of hits at weak binding affinities for these targets.

  15. Heart failure therapy: drugs, genes or stem cells?: by Caroline Telfer.

    Science.gov (United States)

    Harding, Sian

    2013-09-01

    Professor Sian Harding talks to Caroline Telfer, Assistant Commissioning Editor. Professor Sian Harding obtained her PhD in Pharmacology from King's College, London (UK) in 1981. She became Professor of Cardiac Pharmacology at the National Heart and Lung Institute, a division of the Imperial College Faculty of Medicine, in 2002. Her work has been funded by the British Heart Foundation, the Wellcome Trust, the Medical Research Council, the Biochemical and Biophysical Research Council, the The National Centre for the Replacement, Refinement and Reduction of Animals in Research, Pfizer, GlaxoSmithKline and SmithKline Beecham. Harding is former president of the European Section of the International Society for Heart Research and has organized international cardiovascular science meetings for this society, as well as for the European Society of Cardiology. She is the principal investigator for the first UK gene therapy trial aimed at improving cardiac contractility, organized jointly at Harefield and Papworth Hospitals. Harding is a member of the Nuffield Council on Bioethics and the Medical Research Coucil Regenerative Medicine Research Committee, and Director of a recently awarded British Heart Foundation Cardiovascular Regenerative Medicine Centre. She has been elected Fellow of the American Heart Association, European Society of Cardiology, International Society for Heart Research, Society of Biology and British Society of Pharmacology.

  16. Secondary patents in the pharmaceutical industry: missing the wood for the trees?

    Science.gov (United States)

    Kiran, Saritha; Kulkarni, Mohan

    2018-03-01

    The critics of the Innovator pharmaceutical industry allege that secondary patents are trivial modifications over the primary patent, which extend its term and delay the entry of the generics in the market place. The protagonists regard secondary patents a result of continuous research and development (R&D), which help them introduce and protect new, differentiated products. Areas covered: The areas covered are Product life cycle management (PLCM), Drug approval process, Orange book (OB) listed patents, US patent data. Expert opinion: Our analysis of the patents and products of four innovators viz., AstraZeneca, Takeda, Eisai and Wyeth in the field of proton pump inhibitors (PPI's) and Merck and Pfizer in the field of Statins shows that secondary patents help innovators sustain competition against other innovators in the specific product segment. The number of secondary patents listed in OB per NCE depends on the innovators interest in exploiting the NCE, the success of R & D effort and product lifecycle management strategy in the wake of market competition. Market entry decisions of innovators are strategic rather than a mere fallout of the secondary patents granted. Entry of another innovator is more unpredictable and hurts the first entrant more vis a vis the entry of generics who can enter the market when the patents protecting a product are no more enforceable, and hence more predictable. Generic entry in the field of PPI's shows that the term of the primary patent is not extended by the secondary patents.

  17. A clinical plan for MDMA (Ecstasy) in the treatment of posttraumatic stress disorder (PTSD): partnering with the FDA.

    Science.gov (United States)

    Doblin, Rick

    2002-01-01

    The FDA and the Spanish Ministry of Health have concluded that the risk/benefit ratio is favorable under certain circumstances for clinical studies investigating MDMA-assisted psychotherapy. Both agencies have approved pilot studies in chronic posttraumatic stress disorder (PTSD) patients who have failed to obtain relief from at least one course of conventional treatment. These studies, the only ones in the world into the therapeutic use of MDMA, are being funded by a nonprofit research and educational organization, the Multidisciplinary Association for Psychedelic Studies (MAPS, www.maps.org). A rationale is offered explaining why MAPS chose to focus its limited resources on MDMA, and also on PTSD patients. A Clinical Plan is elaborated for the conduct of the "adequate and well-controlled" trials necessary to evaluate the safety and efficacy of MDMA-assisted psychotherapy for PTSD, with the studies estimated to cost about 5 million dollars and to take about five years. The Clinical Plan has been developed, in part, through analysis of the studies conducted by Pfizer in its successful effort to have Zoloft approved by the FDA for use with PTSD patients, and through review of transcripts of the FDA's Psychopharmacologic Drugs Advisory Committee meeting that recommended approval of Zoloft for PTSD.

  18. NEW APPROACHES TO PHARMACOTHERAPY OF RHEUMATOID ARTHRITIS: TOFACITINIB

    Directory of Open Access Journals (Sweden)

    E. L. Nasonov

    2014-01-01

    Full Text Available One of the breakthroughs in pharmacology of the XXI century is the development of a new class of drugs, which are low molecular weight (<1 kDa, chemically synthesized substances (small molecules intended for oral administration. Their point of application is tyrosine kinases, the enzymes involved in regulation of intracellular signaling that deter- mines the biological activity of cytokines. Tofacitinib (TOFA, Tofacitinib, Yakvinus; Pfizer, the first oral reversible inhibitor of JAK approved for treatment of rheumatoid arthritis (RA, is of special interest. The clinical efficacy and low toxicity of TOFA have been proved in a series of phase III randomized placebo-controlled studies, combined under the acronym ORAL, which has included more than 5000 patients with RA. Further research is needed, aimed at assessing the efficacy and safety of TOFA during prolonged use in real-life clinical practice (including through national registers in patients with various forms of RA and comorbid diseases. It is reasonable to conduct «strategic» research of TOFA, designed in accordance with the concept of goal-directed treatment.

  19. An Economic Evaluation of Tofacitinib Treatment in Rheumatoid Arthritis: Modeling the Cost of Treatment Strategies in the United States.

    Science.gov (United States)

    Claxton, Lindsay; Jenks, Michelle; Taylor, Matthew; Wallenstein, Gene; Mendelsohn, Alan M; Bourret, Jeffrey A; Singh, Amitabh; Moynagh, Dermot; Gerber, Robert A

    2016-09-01

    epidemiological data. Sensitivity analyses were conducted to explore the impact of varying key parameters, including treatment-switching probability, product rebate, major rates of adverse drug reaction, and ACR20 rates, on the model outcomes. Tofacitinib combination therapy after MTX failure was associated with the lowest cost per member per month (PMPM) over a 2-year time frame at $5.53, compared with $6.49 for adalimumab, $6.43 for etanercept, $5.95 for certolizumab, and $5.89 for tocilizumab. Similar savings were observed when all biologics were administered as monotherapy. Tofacitinib combination therapy was also associated with the lower PMPM cost compared with adalimumab combination therapy in the TNF-IR analysis. Tofacitinib was also among the lowest cost per ACR20 responder in each analysis. Sensitivity analyses demonstrated that tofacitinib would potentially be cost saving even in the least optimistic scenarios. This analysis suggests that tofacitinib 5 mg BID following MTX failure is a lower cost per patient treatment option when used either as monotherapy or combination therapy, compared with adalimumab, etanercept, certolizumab and tocilizumab biologic regimens. Tofacitinib + MTX in TNF-IR patients was also predicted to be a lower-cost treatment option compared with adalimumab+MTX and was associated with the lowest cost per ACR 20/50/70 responder. This study was funded by Pfizer, which determined the research topic and paid York Health Economics Consortium to develop the analysis and conduct the research. York Health Economics Consortium has received consultancy fees from Pfizer. Gerber, Wallenstein, Mendelsohn, Bourret, Singh, and Moynagh are employees and shareholders of Pfizer. Editorial support was funded by Pfizer and was provided by Claxton, Jenks, and Taylor, who are employees of York Health Economics Consortium. Study concept and design were contributed primarily by Taylor, Jenks, Gerber, and Singh, along with the other authors. Gerber, Moynagh, and Singh

  20. The efficacy and safety of tofacitinib in Asian patients with moderate to severe chronic plaque psoriasis: A Phase 3, randomized, double-blind, placebo-controlled study.

    Science.gov (United States)

    Zhang, JianZhong; Tsai, Tsen-Fang; Lee, Min-Geol; Zheng, Min; Wang, Gang; Jin, HongZhong; Gu, Jun; Li, RuoYu; Liu, QuanZhong; Chen, Jin; Tu, CaiXia; Qi, ChunMei; Zhu, Hua; Ports, William C; Crook, Tim

    2017-10-01

    Tofacitinib is an oral Janus kinase inhibitor. This study assessed tofacitinib efficacy and safety vs placebo in Asian patients with moderate to severe chronic plaque psoriasis. Patients from China mainland, Taiwan, and Korea were randomized 2:2:1:1 to tofacitinib 5mg (N=88), tofacitinib 10mg (N=90), placebo→5mg (N=44), or placebo→10mg (N=44), twice daily (BID) for 52 weeks. Placebo-treated patients advanced to tofacitinib at Week 16. Co-primary efficacy endpoints: proportions of patients achieving Physician's Global Assessment (PGA) response ('clear' or 'almost clear') and proportion achieving ≥75% reduction from baseline Psoriasis Area and Severity Index (PASI75) at Week 16. At Week 16, more patients achieved PGA and PASI75 responses with tofacitinib 5mg (52.3%; 54.6%) and 10mg (75.6%; 81.1%) BID vs placebo (19.3%; 12.5%; all ptofacitinib 5mg and 10mg BID, respectively. Over 52 weeks, 2.2-4.5% of patients across treatment groups experienced serious adverse events, and 1.1-6.8% discontinued due to adverse events. Tofacitinib demonstrated efficacy vs placebo at Week 16 in Asian patients with moderate to severe plaque psoriasis; efficacy was maintained through Week 52. No unexpected safety findings were observed. [NCT01815424]. Copyright © 2017 The Authors and Pfizer Inc. Published by Elsevier B.V. All rights reserved.

  1. Extraction of tacit knowledge from large ADME data sets via pairwise analysis.

    Science.gov (United States)

    Keefer, Christopher E; Chang, George; Kauffman, Gregory W

    2011-06-15

    Pharmaceutical companies routinely collect data across multiple projects for common ADME endpoints. Although at the time of collection the data is intended for use in decision making within a specific project, knowledge can be gained by data mining the entire cross-project data set for patterns of structure-activity relationships (SAR) that may be applied to any project. One such data mining method is pairwise analysis. This method has the advantage of being able to identify small structural changes that lead to significant changes in activity. In this paper, we describe the process for full pairwise analysis of our high-throughput ADME assays routinely used for compound discovery efforts at Pfizer (microsomal clearance, passive membrane permeability, P-gp efflux, and lipophilicity). We also describe multiple strategies for the application of these transforms in a prospective manner during compound design. Finally, a detailed analysis of the activity patterns in pairs of compounds that share the same molecular transformation reveals multiple types of transforms from an SAR perspective. These include bioisosteres, additives, multiplicatives, and a type we call switches as they act to either turn on or turn off an activity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Factors Associated with Bovine Neonatal Pancytopenia (BNP) in Calves: A Case-Control Study

    Science.gov (United States)

    Lambton, Sarah L.; Colloff, Adrian D.; Smith, Richard P.; Caldow, George L.; Scholes, Sandra F. E.; Willoughby, Kim; Howie, Fiona; Ellis-Iversen, Johanne; David, Graham; Cook, Alasdair J. C.; Holliman, Andrew

    2012-01-01

    Bovine neonatal pancytopenia (BNP; previously known as idiopathic haemorrhagic diathesis and commonly known as bleeding calf syndrome) is a novel haemorrhagic disease of young calves which has emerged in a number of European countries during recent years. Data were retrospectively collected during June to November 2010 for 56 case calves diagnosed with BNP between 17 March and 7 June of the same year. These were compared with 58 control calves randomly recruited from herds with no history of BNP. Multivariable logistic regression analysis showed that increased odds of a calf being a BNP case were associated with its dam having received PregSure® BVD (Pfizer Animal Health) vaccination prior to the birth of the calf (odds ratio (OR) 40.78, p<0.001) and its herd of origin being located in Scotland (OR 9.71, p = 0.006). Decreased odds of a calf being a BNP case were associated with the calf having been kept outside (OR 0.11, p = 0.006). The longer that a cattle herd had been established on the farm was also associated with decreased odds of a calf in that herd being a BNP case (OR 0.97, p = 0.011). PMID:22606224

  3. Stimulant use and its impact on growth in children receiving growth hormone therapy: an analysis of the KIGS International Growth Database.

    Science.gov (United States)

    Miller, Bradley S; Aydin, Ferah; Lundgren, Frida; Lindberg, Anders; Geffner, Mitchell E

    2014-01-01

    Children receiving stimulants for attention deficit hyperactivity disorder (ADHD) frequently present to pediatric endocrinology clinics for evaluation and treatment of growth disorders. The worldwide prevalence of stimulant use in children with ADHD also receiving recombinant human growth hormone (rhGH) and the impact on response to rhGH are unknown. Data on children enrolled in the KIGS® (Pfizer International Growth Study) registry were evaluated for the associated diagnosis of ADHD prior to initiation of Genotropin® rhGH. Concomitant stimulant medications and auxological information were captured. Response to rhGH was evaluated using established growth prediction models. The prevalence of ADHD in KIGS was 2.3% (1,748/75,251), with stimulants used in 1.8% (1,326/75,251). Children with idiopathic growth hormone deficiency (IGHD) who received stimulants grew significantly less (1.1 cm) in the first year of rhGH therapy than expected for rhGH-treated non-ADHD IGHD children. After one year of rhGH, idiopathic short stature (ISS) children with ADHD were significantly shorter [0.74 cm (with stimulants) and 0.69 cm (without stimulants)] than non-ADHD ISS children. We demonstrated an impaired response to rhGH in IGHD and ISS children with ADHD. Our findings suggest that the ADHD phenotype, alone or in conjunction with stimulant therapy, may impair the short-term growth response to rhGH.

  4. ALK inhibitors, a pharmaceutical perspective

    Directory of Open Access Journals (Sweden)

    Arturo eGalvani

    2012-02-01

    Full Text Available In 2007, the ALK tyrosine kinase, already known to be translocated and activated in Anaplastic Large Cell Lymphoma, and a few other rare cancers, was described as a potential therapeutic target for a subset of non small-cell lung cancer (NSCLC patients. Clinical proof of concept, culminating in the recent approval by the FDA of the Pfizer drug Xalkori (crizotinib, formerly known as PF-02341066 followed in record time. The drug was approved together with a companion diagnostic, the Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular, Inc. for detection of eligible patients. This remarkable example of the coming of age of personalized medicine in cancer therapy is hopefully only an auspice of things to come in this rapidly developing field. Perhaps unsurprisingly, however, the appearance of clinical acquired resistance to crizotinib has already been observed early on in clinical testing, with the identification of several ALK secondary point mutations which diminish drug efficacy, and which open the way for development of second-generation inhibitors. It is also emerging that acquired resistance to crizotinib may also occur through ALK-independent mechanisms, which still need to be elucidated in detail.

  5. Launching biosimilar rituximab: an industry opinion on biosimilar uptake in Europe.

    Science.gov (United States)

    Trollope, Richard; Johnson, Sue; Ireland, Henry

    2017-06-01

    Richard Trollope and Sue Johnson talk with Henry Ireland, Senior Editor about the recent approval of biosimilar rituximab (Truxima ® ) & the current state of biosimilar uptake across Europe Richard Trollope, Head of Biosimilars, Mundipharma International Limited, qualified as a biochemist before joining Wyeth's commercial operations, prior to its acquisition by Pfizer. Richard later joined Yamanouchi Pharmaceuticals (now Astellas Pharma). His fascination with oncology led him to join Mundipharma in Europe and after joining the company's UK arm (Napp Pharmaceuticals Limited), Richard began his journey in biosimilars. He now heads up the biosimilar franchise at Mundipharma International as it launches biosimilar rituximab (Truxima ® ) - the first biosimilar monoclonal antibody for the treatment of cancer, which will be distributed by Napp Pharmaceuticals in the UK. Sue Johnson, PhD, Medical Insights at Mundipharma International Limited, is a scientist by background and completed her postdoc fellowship at Harvard Medical School. On returning to the UK, she began her career in the pharmaceutical industry, working in UK Medical Affairs before transitioning to a European role with Mundipharma 2 years ago, where she leads on Medical Insights for the biosimilars franchise.

  6. Maraviroc: perspectives for use in antiretroviral-naive HIV-1-infected patients.

    Science.gov (United States)

    Vandekerckhove, Linos; Verhofstede, Chris; Vogelaers, Dirk

    2009-06-01

    Maraviroc (Pfizer's UK-427857, Selzentry or Celsentri outside the USA) is the first agent in the new class of oral HIV-1 entry inhibitors to acquire approval by the US Food and Drug Administration and the European Medicine Agency. Considering the mechanism of action, it is expected that this drug will be effective only in a subpopulation of HIV-1-infected people, namely those harbouring the R5 virus. The favourable toxicity profile of the drug has been demonstrated in Phase III clinical trials in treatment-naive (MERIT) and treatment-experienced (MOTIVATE) patients. In the latter population, maraviroc showed a superior antiviral efficacy and immunological activity compared with optimized backbone therapy + placebo. However, in MERIT, a prospective double-blind, randomized trial in treatment-naive patients, maraviroc + zidovudine/lamivudine failed to prove non-inferiority to efavirenz + zidovudine/lamivudine as standard of care regimen in the 48 week intention-to-treat analysis. Using an assay with higher sensitivity for minority CXCR4-using (X4) HIV variants (the enhanced Trofile assay-Monogram), non-inferiority was reached for the maraviroc- versus efavirenz-based combination. These data indicate the important impact of the sensitivity of tropism testing on treatment outcome of maraviroc-containing regimens. This paper discusses both the prospective and retrospective analyses of the MERIT data and highlights the impact of these results on daily practice in HIV care.

  7. A drug's life: the pathway to drug approval.

    Science.gov (United States)

    Keng, Michael K; Wenzell, Candice M; Sekeres, Mikkael A

    2013-10-01

    In the United States, drugs and medical devices are regulated by the US Food and Drug Administration (FDA). A drug must undergo rigorous testing prior to marketing to and medical use by the general public. The FDA grants marketing approval for drug products based on a comprehensive review of safety and efficacy data. This review article explains the history behind the establishment of the FDA and examines the historical legislation and approval processes for drugs, specifically in the fields of medical oncology and hematology. The agents imatinib (Gleevec, Novartis) and decitabine (Dacogen, Eisai) are used to illustrate both the current FDA regulatory process-specifically the orphan drug designation and accelerated approval process-and why decitabine failed to gain an indication for acute myeloid leukemia. The purpose and construct of the Oncologic Drugs Advisory Committee are also discussed, along with examples of 2 renal cell cancer drugs-axitinib (Inlyta, Pfizer) and tivozanib-that used progression-free survival as an endpoint. Regulatory approval of oncology drugs is the cornerstone of the development of new treatment agents and modalities, which lead to improvements in the standard of cancer care. The future landscape of drug development and regulatory approval will be influenced by the new breakthrough therapy designation, and choice of drug will be guided by genomic insights.

  8. African American patients' attitudes toward proactive health behaviors after exposure to direct-to-consumer advertising.

    Science.gov (United States)

    Yang, Yi; Gourley, Dick R; Gourley, Greta A; Faris, Richard J; Womeodu, Robin J; Yang, Jun; Likens, Carol C

    2010-05-01

    Previous research on direct-to-consumer advertising (DTCA) has not focused exclusively on the African American population. The purpose of this study was to explore African Americans' attitudes toward proactive health behaviors following exposure to DTCA of atorvastatin calcium (Lipitor, Pfizer Inc). One-hundred fifty African American patients participated in the study. Participants' functional health literacy and health locus of control were assessed. The participants were asked to view a DTCA of Lipitor, followed by face-to-face interviews. After watching the DTCA of Lipitor, 89.4% of participants agreed that they would talk to their physician about their cholesterol, 88.6% agreed that they would ask their physician to test their cholesterol level, and 47.3% agreed that they would ask their physician to write them a prescription for Lipitor. Those who had a history of high cholesterol were more likely to agree to ask their physician to test their cholesterol levels. Low household income, having public health insurance, and prior experience with taking Lipitor were significant positive predictors of patients agreeing to ask their physician to write a prescription of the advertised drug. African American patients showed favorable attitudes toward proactive health behaviors after exposure to DTCA of Lipitor.

  9. Magnetic resonance imaging and relaxometry to study water transport mechanisms in a commercially available gastrointestinal therapeutic system (GITS) tablet.

    Science.gov (United States)

    Broadbent, Amber L; Fell, Rob J; Codd, Sarah L; Lightley, Kim A; Konagurthu, Sanjay; Koehler-King, Dory G; Seymour, Joseph D

    2010-09-15

    The hydration of 4 mg Cardura XL (Pfizer), a commercially available gastrointestinal therapeutic system (GITS) tablet, was investigated using magnetic resonance imaging (MRI). A short echo time (T(e)=2.81 ms) technique for MRI of the hydration of a GITS tablet was implemented. From the MR images, signal intensity profiles were generated and interpreted in the context of diffusive and osmotic transport mechanisms. A distinct transition from diffusive to osmotic transport was measured at a timescale relevant to the measured drug release time. Diffusion and osmotic rate coefficients for water in the drug and polymer sweller layers of the tablet were quantified. Spin-lattice T(1) and spin-spin T(2) relaxation times of the water signal from within the tablet were measured as a function of hydration time in order to incorporate the effects of relaxation into interpretation of signal intensity and provide unique information on the distribution of water in different physical and chemical environments within the tablet. Copyright 2010 Elsevier B.V. All rights reserved.

  10. STEPS: A NARRATIVE ACCOUNT OF A GABAPENTIN SEEDING TRIAL

    Science.gov (United States)

    Krumholz, Samuel D.; Egilman, David S.; Ross, Joseph S.

    2012-01-01

    Background Seeding trials, clinical studies conducted by pharmaceutical companies for marketing purposes, have rarely been described in detail. Methods We examined all documents relating to the clinical trial Study of Neurontin: Titrate to Effect, Profile of Safety (STEPS) produced during the Neurontin marketing, sales practices and product liability litigation, including company internal and external correspondence, reports, and presentations, as well as depositions elicited in legal proceedings of Harden Manufacturing v. Pfizer and Franklin v. Warner-Lambert, the majority of which were created between 1990 and 2009. Using a systematic search strategy, we identified and reviewed all documents related to the STEPS trial, in order to identify key themes related to the trial’s conduct and determine the extent of marketing involvement in its planning and implementation. Results Documents demonstrated that STEPS was a seeding trial posing as a legitimate scientific study. Documents consistently described the trial itself, not trial results, to be a marketing tactic in the company’s marketing plans. Documents demonstrated that several external sources questioned the validity of the study before execution, and that data quality during the study was often compromised. Furthermore, documents described company analyses examining the impact of participating as a STEPS investigator on rates and dosages of gabapentin prescribing, finding a positive association. None of these findings were reported in two published papers. Conclusions The STEPS trial was a seeding trial, used to promote gabapentin and increase prescribing among investigators, and marketing was extensively involved in its planning and implementation. PMID:21709111

  11. EFEITO DA ADIÇÃO DE NUTRIENTES NA FERMENTAÇÃO ALCOÓLICA DE MEIO DE CULTIVO ELABORADO COM FÉCULA DE MANDIOCA

    Directory of Open Access Journals (Sweden)

    EDWIL APARECIDA LUCCA GATTAS

    2007-01-01

    Full Text Available O objetivo do trabalho foi verificar o efeito da adição de sulfato de amônio ou uréia em meios contendo KH2PO4, extrato de levedura e fécula de mandioca dextrinizada na velocidade de produção de etanol em processo de sacarificação – fermentação simultâneas. Ficou demonstrada a necessidade de suplementação do meio de cultivo com nitrogênio, podendo ser utilizados com este fim tanto o sulfato de amônio como a uréia. Nos meios enriquecidos com nutrientes houve aumento na velocidade de fermentação de 41%. Na etapa da sacarificação levada a efeito na temperatura ótima da enzima, observou-se que é indiferente empregar-se as amiloglicosidases comercializadas pela Novo Industri S.A. (Spiritamylase e SAN 200 OL ou pela Pfizer, sempre precedidas pela liquefação com alfa-amilase da Okochi Ltda.

  12. Hardness, function, emotional well-being, satisfaction and the overall sexual experience in men using 100-mg fixed-dose or flexible-dose sildenafil citrate.

    Science.gov (United States)

    Ströberg, P; Kaminetsky, J C; Park, N C; Goldfischer, E R; Creanga, D L; Stecher, V J

    2010-01-01

    The prescribing information for sildenafil citrate (VIAGRA, Pfizer, New York, NY, USA) recommends flexible dosing (50 mg initially, adjusted to 100 or 25 mg based on effectiveness and tolerability) in most men with erectile dysfunction (ED). In many men, however, 100 mg may be the most appropriate initial dose because it would reduce the need for titration and could prevent discouragement and treatment abandonment should 50 mg be insufficient. Results of two previously published double-blind, placebo-controlled sildenafil trials of similar design except for a fixed-dose vs flexible-dose regimen were analyzed. Relative to the flexible-dose, approximately one-third more men were satisfied with an initial and fixed dose of 100 mg. In addition, tolerability was similar, and improvements from baseline in outcomes on validated, ED-specific, patient-reported questionnaires were either similar (erectile function and the percentage of completely hard and fully rigid erections) or greater (emotional well-being and the overall sexual experience). The similarity in outcomes is not surprising given that almost 90% of the men in the flexible-dose trial titrated to 100 mg after 2 weeks. These data suggest prescription of an initial dose of 100 mg for men with ED, except in those for whom it is inappropriate.

  13. Factors contributing to intervention fidelity in a multi-site chronic disease self-management program.

    Science.gov (United States)

    Perrin, Karen M; Burke, Somer Goad; O'Connor, Danielle; Walby, Gary; Shippey, Claire; Pitt, Seraphine; McDermott, Robert J; Forthofer, Melinda S

    2006-10-26

    Disease self-management programs have been a popular approach to reducing morbidity and mortality from chronic disease. Replicating an evidence-based disease management program successfully requires practitioners to ensure fidelity to the original program design. The Florida Health Literacy Study (FHLS) was conducted to investigate the implementation impact of the Pfizer, Inc. Diabetes Mellitus and Hypertension Disease Self-Management Program based on health literacy principles in 14 community health centers in Florida. The intervention components discussed include health educator recruitment and training, patient recruitment, class sessions, utilization of program materials, translation of program manuals, patient retention and follow-up, and technical assistance. This report describes challenges associated with achieving a balance between adaptation for cultural relevance and fidelity when implementing the health education program across clinic sites. This balance was necessary to achieve effectiveness of the disease self-management program. The FHLS program was implemented with a high degree of fidelity to the original design and used original program materials. Adaptations identified as advantageous to program participation are discussed, such as implementing alternate methods for recruiting patients and developing staff incentives for participation. Effective program implementation depends on the talent, skill and willing participation of clinic staff. Program adaptations that conserve staff time and resources and recognize their contribution can increase program effectiveness without jeopardizing its fidelity.

  14. Factors contributing to intervention fidelity in a multi-site chronic disease self-management program

    Directory of Open Access Journals (Sweden)

    Pitt Seraphine

    2006-10-01

    Full Text Available Abstract Background and objectives Disease self-management programs have been a popular approach to reducing morbidity and mortality from chronic disease. Replicating an evidence-based disease management program successfully requires practitioners to ensure fidelity to the original program design. Methods The Florida Health Literacy Study (FHLS was conducted to investigate the implementation impact of the Pfizer, Inc. Diabetes Mellitus and Hypertension Disease Self-Management Program based on health literacy principles in 14 community health centers in Florida. The intervention components discussed include health educator recruitment and training, patient recruitment, class sessions, utilization of program materials, translation of program manuals, patient retention and follow-up, and technical assistance. Results This report describes challenges associated with achieving a balance between adaptation for cultural relevance and fidelity when implementing the health education program across clinic sites. This balance was necessary to achieve effectiveness of the disease self-management program. The FHLS program was implemented with a high degree of fidelity to the original design and used original program materials. Adaptations identified as advantageous to program participation are discussed, such as implementing alternate methods for recruiting patients and developing staff incentives for participation. Conclusion Effective program implementation depends on the talent, skill and willing participation of clinic staff. Program adaptations that conserve staff time and resources and recognize their contribution can increase program effectiveness without jeopardizing its fidelity.

  15. Möbius Syndrome: Misoprostol Use and Speech and Language Characteristics

    Directory of Open Access Journals (Sweden)

    Guedes, Zelita Caldeira Ferreira

    2014-03-01

    Full Text Available Introduction Möbius syndrome (MS; VI and VII palsy is a rare disease that in Brazil has a great frequency because of the use of misoprostol during pregnancy. Objective Verify if the speech and language performance of children with MS whose mothers reported use of misoprostol (Cytotec, Pfizer, Connecticut, USA are different from the performance of children of mothers who did not report use. Methods The stomatognathic system beyond receptive and expressive language and speech was evaluated in children with MS, and their mothers were questioned whether they used misoprostol during the pregnancy. Results During the interview, 61.11% of mothers reported that they took misoprostol during the pregnancy. Most of the subjects (83.3% whose mothers took misoprostol presented bilateral palsy beyond bad mobility of the tongue (90.9% and speech disorders (63.6%. Conclusion The number of mothers who took misoprostol without knowing the risk for MS was great. The lack of facial expressions and speech disorders were common characteristics of the individuals with MS, whether the mothers took misoprostol during the pregnancy or not.

  16. Drug-like properties and the causes of poor solubility and poor permeability.

    Science.gov (United States)

    Lipinski, C A

    2000-01-01

    There are currently about 10000 drug-like compounds. These are sparsely, rather than uniformly, distributed through chemistry space. True diversity does not exist in experimental combinatorial chemistry screening libraries. Absorption, distribution, metabolism, and excretion (ADME) and chemical reactivity-related toxicity is low, while biological receptor activity is higher dimensional in chemistry space, and this is partly explainable by evolutionary pressures on ADME to deal with endobiotics and exobiotics. ADME is hard to predict for large data sets because current ADME experimental screens are multi-mechanisms, and predictions get worse as more data accumulates. Currently, screening for biological receptor activity precedes or is concurrent with screening for properties related to "drugability." In the future, "drugability" screening may precede biological receptor activity screening. The level of permeability or solubility needed for oral absorption is related to potency. The relative importance of poor solubility and poor permeability towards the problem of poor oral absorption depends on the research approach used for lead generation. A "rational drug design" approach as exemplified by Merck advanced clinical candidates leads to time-dependent higher molecular weight, higher H-bonding properties, unchanged lipophilicity, and, hence, poorer permeability. A high throughput screening (HTS)-based approach as exemplified by unpublished data on Pfizer (Groton, CT) early candidates leads to higher molecular weight, unchanged H-bonding properties, higher lipophilicity, and, hence, poorer aqueous solubility.

  17. Patient Characteristics, Health Care Resource Utilization, and Costs Associated with Treatment-Regimen Failure with Biologics in the Treatment of Psoriasis.

    Science.gov (United States)

    Foster, Shonda A; Zhu, Baojin; Guo, Jiaying; Nikai, Enkeleida; Ojeh, Clement; Malatestinic, William; Goldblum, Orin; Kornberg, Lori J; Wu, Jashin J

    2016-04-01

    variance for continuous variables and chi-square tests for categorical variables without adjustment. Cost differences were compared using the propensity score-adjusted bin bootstrapping method. Overall, 2,146 patients met the enrollment criteria. The mean age was 45.1 years. Of these patients, 41.5% were considered treatment-regimen failures. Among treatment-regimen failures, 53% were females, and among non-treatment-regimen failures, 61% were male. Patients who experienced treatment-regimen failure had higher incidences of comorbid cerebrovascular disease, hypertension, chronic pulmonary disease, depression, and anxiety in the pre-index period and were more likely to use concomitant topicals (67.0% vs. 58.4%; P different characteristics and incurred higher all-cause health care costs than did patients without treatment-regimen failure during the pre-index period. This study was supported by Eli Lilly and Company. Foster, Zhu, Guo, Nikai, Malatestinic, Ojeh, and Goldblum are full-time employees and stockholders of Eli Lilly and Company. Kornberg is a full-time employee of INC Research, which was contracted by Eli Lilly to assist with medical writing. Wu has received research funding from AbbVie, Amgen, Coherus Biosciences, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Regeneron, and Sandoz; he is a consultant for AbbVie, Amgen, Celgene, Dermira, DUSA Pharmaceuticals, Eli Lilly, and Pfizer. Study concept was developed by Foster, Ojeh, Malatestinic, and Goldblum. Zhu and Guo, along with Foster, took the lead in data collection, and data interpretation was performed by Nikai, Wu, and Foster, with assistance from the other authors. The manuscript was primarily written by Kornberg, along with Foster, with assistance from the other authors. All of the authors were involved with manuscript revision.

  18. Burden of methicillin-resistant Staphylococcus aureus pneumonia among hospitalized patients in Lebanon and Saudi Arabia

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    Althaqafi AO

    2017-02-01

    Full Text Available Abdulhakeem O Althaqafi,1 Madonna J Matar,2 Rima Moghnieh,3 Adel F Alothman,4 Thamer H Alenazi,5 Fayssal Farahat,1 Shelby Corman,6 Caitlyn T Solem,6 Nirvana Raghubir,7 Cynthia Macahilig,8 Seema Haider,9 Jennifer M Stephens6 1Department of Infection Prevention and Control, King Abdullah International Medical Research Center, King Saud bin AbdulAziz University for Health Sciences, Jeddah, Kingdom of Saudi Arabia; 2Department of Infectious Disease, Notre Dame de Secours University Hospital, Byblos, 3Makassed General Hospital, Beirut, Lebanese Republic; 4Department of Medicine, King Abdulaziz Medical City, Central Region, Ministry of National Guard Health Affairs, 5Infection Prevention & Control Department, King Abdulaziz Medical City-Riyadh (KAMC, Kingdom of Saudi Arabia; 6Real World Evidence: Data Analytics Center of Excellence, Pharmerit International, Bethesda, MD, 7Medical Affairs, Pfizer, New York, NY, 8Medical Data Analytics, Parsippany, NJ, 9Outcomes & Evidence, Global Health and Value, Pfizer, Groton, CT, USA Objectives: The objective of this study is to describe the real-world treatment patterns and burden of suspected or confirmed methicillin-resistant Staphylococcus aureus (MRSA pneumonia in Saudi Arabia and Lebanon. Methods: A retrospective chart review study evaluated 2011–2012 data from hospitals in Saudi Arabia and Lebanon. Patients were included if they had been discharged with a diagnosis of MRSA pneumonia, which was culture proven or suspected based on clinical criteria. Hospital data were abstracted for a random sample of patients to capture demographics (eg, age and comorbidities, treatment patterns (eg, timing and use of antimicrobials, hospital resource utilization (eg, length of stay, and clinical outcomes (eg, clinical status at discharge and mortality. Descriptive results were reported using frequencies or proportions for categorical variables and mean and standard deviation for continuous variables. Results: Chart

  19. Burden and treatment patterns of invasive fungal infections in hospitalized patients in the Middle East: real-world data from Saudi Arabia and Lebanon

    Directory of Open Access Journals (Sweden)

    Alothman AF

    2017-02-01

    Full Text Available Adel F Alothman,1 Abdulhakeem O Althaqafi,2 Madonna J Matar,3 Rima Moghnieh,4 Thamer H Alenazi,1 Fayssal M Farahat,2 Shelby Corman,5 Caitlyn T Solem,5 Nirvana Raghubir,6 Cynthia Macahilig,7 Claudie Charbonneau,8 Jennifer M Stephens5 1College of Medicine, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 2Department of Infection Prevention and Control, King Abdullah International Medical Research Center, King Saud bin AbdulAziz University for Health Sciences, King AbdulAziz Medical City, Jeddah, Saudi Arabia; 3Department of Infectious Disease, Notre Dame de Secours University Hospital, Byblos, Lebanon; 4Department of Internal Medicine, Makassed General Hospital, Beirut, Lebanon; 5Real-world Evidence/Data Analytics Center of Excellence, Pharmerit International, Bethesda, MD, USA; 6Pfizer, New York, NY, 7Medical Data Analytics, Parsippany, NJ, USA; 8Pfizer International Operation, Paris, France Objectives: The objective of this study was to document the burden and treatment patterns associated with invasive fungal infections (IFIs due to Candida and Aspergillus species in Saudi Arabia and Lebanon. Methods: A retrospective chart review study was conducted using data recorded from 2011 to 2012 from hospitals in Saudi Arabia and Lebanon. Patients were included if they had been discharged with a diagnosis of IFI due to Candida or Aspergillus, which was culture proven or suspected based on clinical criteria. Hospital data were abstracted for a random sample of patients to capture demographics, treatment patterns, hospital resource utilization, and clinical outcomes. Descriptive results were reported. Results: Five hospitals participated and provided data on 102 patients with IFI (51 from Lebanon and 51 from Saudi Arabia. The mean age of the patients was 55 years, and 55% were males. Comorbidities included diabetes (41%, coronary artery disease (24%, leukemia (19%, moderate

  20. A Phase I study evaluating the effect of age and weight on the pharmacokinetics of an injectable formulation of diclofenac solubilized with hydroxypropyl-β-cyclodextrin

    Directory of Open Access Journals (Sweden)

    Goldwater R

    2016-12-01

    Full Text Available Ronald Goldwater,1 William G Kramer,2 Douglas A Hamilton,3,4 Eric Lang,4,5 Jianyuan Wang,4 Donna E Madden,4 Peter G Lacouture,6,7 Atulkumar Ramaiya,8 Daniel B Carr4,9 1PAREXEL International, Baltimore, MD, 2Kramer Consulting, LLC, North Potomac, MD, 3New Biology Ventures, LLC, San Mateo, CA, 4Javelin Pharmaceuticals, Cambridge, MA (now Hospira, a Pfizer company, Lake Forest, IL, USA, 5Covance, Princeton, NJ, 6Magidom Discovery, LLC, Lindenhurst, IL, 7Brown University School of Medicine, Providence, RI, 8Global Medical Affairs, Hospira, a Pfizer company, Lake Forest, IL, 9Department of Anesthesiology, Tufts Medical Center, Boston, MA, USA Purpose: The analgesic and opioid-sparing effects of nonsteroidal anti-inflammatory drugs can be beneficial in postoperative populations. Hydroxypropyl-β-cyclodextrin (HPβCD-diclofenac is an injectable formulation of diclofenac solubilized with HPβCD that is administered as a low-volume intravenous bolus. This open-label, single-dose study examined the effects of age and weight on the pharmacokinetic (PK profile of HPβCD-diclofenac. Methods: Eighty-eight adult volunteers were enrolled. An age-based cohort included 34 subjects 55–82 years old stratified into three groups and receiving HPβCD-diclofenac 18.75 mg. A weight-based cohort included 54 subjects stratified into five groups based on body weight and body mass index and receiving HPβCD-diclofenac 37.5 mg. PK analysis was performed on blood samples collected predosing and at predefined intervals (5, 10, 20, 30, and 45 minutes; 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, and 18 hours postdosing. Diclofenac PK parameters were examined in the individual cohorts, and regression analyses of the relationship between age, weight, and PK parameters were performed on pooled data from all enrolled subjects. Results: Examination of the age-based cohort revealed similar diclofenac PK parameters across age groups. PK parameters were likewise similar across weight groups

  1. Randomized noninferiority clinical trial evaluating 3 commercial dry cow mastitis preparations: I. Quarter-level outcomes.

    Science.gov (United States)

    Arruda, A G; Godden, S; Rapnicki, P; Gorden, P; Timms, L; Aly, S S; Lehenbauer, T W; Champagne, J

    2013-07-01

    The study objective was to compare the efficacy of 3 commercial dry cow mastitis formulations regarding quarter-level prevalence of intramammary infections (IMI) postcalving, cure of preexisting infections over the dry period, prevention of new infections during the dry period, and risk for a clinical mastitis case between calving and 100d in milk (DIM). A total of 1,091 cows (4,364 quarters) from 6 commercial dairy herds in 4 different states (California, Iowa, Minnesota, and Wisconsin) were enrolled and randomized to 1 of the 3 treatments at dry-off: Quartermaster (QT; 1,000,000 IU of procaine penicillin G and 1 g of dihydrostreptomycin; Pfizer Animal Health, New York, NY), Spectramast DC (SP; 500 mg of ceftiofur hydrochloride; Pfizer Animal Health), or ToMorrow Dry Cow (TM; 300mg of cephapirin benzathine; Boehringer Ingelheim Vetmedica Inc., St. Joseph, MO). Quarter milk samples were collected for routine bacteriological culture before dry cow therapy treatment at dry-off, 0 to 6 DIM, and 7 to 13 DIM and an on-farm record-keeping system was used to retrieve data on clinical mastitis cases. Noninferiority analysis was used to evaluate the effect of treatment on the primary outcome, risk for a bacteriological cure during the dry period. Multivariable logistic regression techniques were used to describe the effect of treatment on risk for presence of IMI postcalving and risk of a new IMI during the dry period. Cox proportional hazards regression was used to describe the effect of treatment on the risk and time for quarters to experience an episode of clinical mastitis between calving and 100 DIM. The overall crude quarter-level prevalence of infection at dry-off was 19.2%. The most common pathogen isolated from milk samples at dry-off was coagulase-negative Staphylococcus, followed by Aerococcus spp. and other Streptococcus spp. Noninferiority analysis showed no effect of treatment on risk for a cure between dry-off and calving [least squares means (LSM): QT=93

  2. Treatment patterns, resource utilization, and outcomes among hospitalized patients with methicillin-resistant Staphylococcus aureus complicated skin and soft tissue infections in Lebanon and Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Matar MJ

    2017-02-01

    Full Text Available Madonna J Matar,1 Rima Moghnieh,2 Adel F Alothman,3 Abdulhakeem O Althaqafi,4 Thamer H Alenazi,3 Fayssal M Farahat,4 Shelby Corman,5 Caitlyn T Solem,5 Nirvana Raghubir,6 Cynthia Macahilig,7 Seema Haider,8 Jennifer M Stephens5 1Department of Infectious Diseases, Notre Dame des Secours University Hospital, Jbeil, Lebanon; 2Department of Internal Medicine, Makassed General Hospital, Beirut, Lebanon; 3College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; 4King Abdullah International Medical Research Center, Infection Prevention and Control, King AbdulAziz Medical City, King Saud bin AbdulAziz University for Health Sciences, Jeddah, Saudi Arabia; 5Pharmerit International, Real-World Evidence/Data Analytics, Bethesda, MD, 6Pfizer, New York, NY, 7Medical Data Analytics, Parsippany, NJ, 8Pfizer, Groton, CT, USA Objectives: To describe treatment patterns and medical resource use for methicillin-resistant Staphylococcus aureus (MRSA complicated skin and soft tissue infections (cSSTI in Saudi Arabia and Lebanon in terms of drug selection against the infecting pathogen as well as hospital resource utilization and clinical outcomes among patients with these infections. Methods: This retrospective chart review study evaluated 2011–2012 data from five hospitals in Saudi Arabia and Lebanon. Patients were included if they had been discharged with a diagnosis of MRSA cSSTI, which was culture-proven or suspected based on clinical criteria. Hospital data were abstracted for a random sample of patients with each infection type to capture demographics, treatment patterns, hospital resource utilization, and clinical outcomes. Statistical analysis was descriptive. Results: Data were abstracted from medical records of 87 patients with MRSA cSSTI; mean age 52.4±25.9 years and 61% male. Only 64% of patients received an MRSA active initial therapy, with 56% of first

  3. Evaluation of Real-World Experience with Tofacitinib Compared with Adalimumab, Etanercept, and Abatacept in RA Patients with 1 Previous Biologic DMARD: Data from a U.S. Administrative Claims Database.

    Science.gov (United States)

    Harnett, James; Gerber, Robert; Gruben, David; Koenig, Andrew S; Chen, Connie

    2016-12-01

    generated similar findings to the unadjusted treatment patterns. Tofacitinib had lower adjusted 12-month post-index mean RA-related total costs ($23,568) versus ADA ($29,278; P tofacitinib was more commonly used as monotherapy and yielded at least comparable persistence and adherence with lower adjusted mean RA-related total costs versus ADA, ETN, and ABA. Further analysis is warranted given the greater 12-month pre-index bDMARD use and RA-related costs for tofacitinib versus bDMARDs. This study was sponsored by Pfizer. Harnett, Gerber, Gruben, Koenig, and Chen are employees and shareholders of Pfizer. Some data reported in this manuscript have been previously presented at the Academy of Managed Care Nexus 2015; Orlando, Florida; October 26-29, 2015, and was submitted in abstract form to the European League Against Rheumatism Congress; London, United Kingdom; June 8-11, 2016. All authors were involved in the conception and design of this study. Harnett and Gruben were involved in data collection and analysis. All authors interpreted the data, critically reviewed and revised the manuscript, and read and approved the final manuscript.

  4. The prevalence of probable neuropathic pain in the US: results from a multimodal general-population health survey

    Directory of Open Access Journals (Sweden)

    DiBonaventura MD

    2017-11-01

    Full Text Available Marco D DiBonaventura,1 Alesia Sadosky,2 Kristen Concialdi,1 Markay Hopps,2 Ian Kudel,1 Bruce Parsons,2 Joseph C Cappelleri,3 Patrick Hlavacek,2 Andrea H Alexander,2 Brett R Stacey,4 John D Markman,5 John T Farrar6 1Health Outcomes Practice, Kantar Health, 2Pfizer Inc, New York, NY, 3Pfizer Inc, Groton, CT, 4University of Washington, Seattle, WA, 5University of Rochester School of Medicine and Dentistry, Rochester, NY, 6University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, US Background: The prevalence of neuropathic pain (NeP has been estimated within specific health conditions; however, there are no published data on its broad prevalence in the US. The current exploratory study addresses this gap using the validated PainDetect questionnaire as a screener for probable NeP in a general-population health survey conducted with a multimodal recruitment strategy to maximize demographic representativeness. Materials and methods: Adult respondents were recruited from a combination of Internet panels, telephone lists, address lists, mall-based interviews, and store-receipt invitations using a random stratified-sampling framework, with strata defined by age, sex, and race/ethnicity. Older persons and minorities were oversampled to improve prevalence estimates. Results were weighted to match the total adult US population using US Census data. Demographic information was collected, and respondents who experienced physical pain in the past 12 months completed the PainDetect and provided additional pain history. A cutoff score of 19 or greater on the PainDetect was used to define probable NeP. Results: A total of 24,925 respondents (average response rate 2.5% provided demographic data (52.2% female, mean age 51.5 years; 15,751 respondents reported pain (63.7%, of which 2,548 (15.7%, 95% confidence interval 14.9%–16.5% had probable NeP based on the PainDetect, which was 10% (95% confidence interval 9.5%–10.5% of all respondents. Among

  5. A cross-sectional study examining the psychometric properties of the painDETECT measure in neuropathic pain

    Directory of Open Access Journals (Sweden)

    Cappelleri JC

    2015-04-01

    Full Text Available Joseph C Cappelleri,1 Vijaya Koduru,2 E Jay Bienen,3 Alesia Sadosky41Pfizer Inc, Groton, CT, USA; 2Eliassen Group, New London, CT, USA; 3Outcomes Research Consultant, New York, NY, USA; 4Pfizer Inc, New York, NY, USABackground: Similarities and differences on the nine-item and seven-item versions of painDETECT, a patient-reported screener to identify neuropathic pain (NeP, have not been psychometrically explored across NeP conditions.Methods: Scores on the nine-item painDETECT (seven pain symptom items, one pain course pattern item, one pain radiation item range from -1 to 38; scores ≥19 indicate NeP is likely (>90% probability. The seven-item version (only pain symptoms score range is 0 to 35. painDETECT was administered to subjects with confirmed diagnoses of human immunodeficiency virus-related peripheral NeP (HIVP (n=103, spinal cord injury-related NeP (SCI (n=103, small fiber neuropathy (n=100, painful diabetic peripheral neuropathy (n=112, posttrauma/postsurgical NeP (n=100, and NeP in chronic low back pain (n=106 identified during office visits to US community-based physicians. Analysis of covariance compared mean scores (adjusted for age, sex, race, ethnicity, time since NeP diagnosis, and number of comorbidities on the nine-item and seven-item versions of painDETECT. Cronbach's alpha assessed internal consistency reliability, and corrected item-to-total correlations assessed item-level discrimination.Results: The adjusted mean nine-item scores ranged from 21.0 (SCI to 24.3 (small fiber neuropathy. Differences between conditions were either trivial or small-to-medium in magnitude. Cronbach's alpha gave overall internal consistency reliability of 0.76, with a range of 0.63 (SCI to 0.82 (HIVP. Mean scores and Cronbach's alphas for the seven-item version were generally similar to the nine-item version. Corrected item-to-total correlations adequately discriminated all pain symptom items on both painDETECT versions for each condition (0.3

  6. Modeling the longitudinal latent effect of pregabalin on self-reported changes in sleep disturbances in outpatients with generalized anxiety disorder managed in routine clinical practice

    Directory of Open Access Journals (Sweden)

    Ruiz MA

    2015-08-01

    Full Text Available Miguel A Ruiz,1 Enrique Álvarez,2 Jose L Carrasco,3 José M Olivares,4 María Pérez,5 Javier Rejas6 1Department of Methodology, School of Psychology, Universidad Autónoma de Madrid, Madrid, 2Department of Psychiatry, Hospital de la Santa Creu i San Pau, Barcelona, 3Department of Psychiatry, Hospital Clínico San Carlos, Madrid, 4Department of Psychiatry, Hospital Meixoeiro, Complejo Hospitalario Universitario, Vigo, 5Medical Department, Pfizer, S.L.U., Alcobendas, Madrid, 6Health Economics and Outcomes Research Department, Pfizer, S.L.U., Alcobendas, Madrid, Spain Background: Anxiety disorders are among the most common psychiatric illnesses, with generalized anxiety disorder (GAD being one of the most common. Sleep disturbances are highly prevalent in GAD patients. While treatment with pregabalin has been found to be associated with significant improvement in GAD-related sleep disturbance across many controlled clinical trials, mediational analysis has suggested that a substantial portion of this effect could be the result of a direct effect of pregabalin. Thus, the objective of this study was to model the longitudinal latent effect of pregabalin or usual care (UC therapies on changes in sleep in outpatients with GAD under routine clinical practice. Methods: Male and female GAD outpatients, aged 18 years or above, from a 6-month prospective noninterventional trial were analyzed. Direct and indirect effects of either pregabalin or UC changes in anxiety symptoms (assessed with Hamilton Anxiety Scale and sleep disturbances (assessed with Medical Outcomes Study-Sleep Scale [MOS-S] were estimated by a conditional latent curve model applying structural equation modeling. Results: A total of 1,546 pregabalin-naïve patients were analyzed, 984 receiving pregabalin and 562 UC. Both symptoms of anxiety and sleep disturbances were significantly improved in both groups, with higher mean (95% confidence interval score reductions in subjects receiving

  7. Effectiveness of pregabalin for the treatment of chronic low back pain with accompanying lower limb pain (neuropathic component: a non-interventional study in Japan

    Directory of Open Access Journals (Sweden)

    Taguchi T

    2015-08-01

    Full Text Available Toshihiko Taguchi,1 Ataru Igarashi,2 Stephen Watt,3 Bruce Parsons,3 Alesia Sadosky,3 Kazutaka Nozawa,4 Kazuhiro Hayakawa,4 Tamotsu Yoshiyama,4 Nozomi Ebata,4 Koichi Fujii4 1Department of Orthopaedic Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan; 2Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan; 3Pfizer Inc., New York, NY, USA; 4Pfizer Japan, Inc., Tokyo, Japan Objective: To evaluate the impact of pregabalin on sleep, pain, function, and health status in patients with chronic low back pain with accompanying neuropathic pain (CLBP-NeP under routine clinical practice. Methods: This prospective, non-interventional, observational study enrolled Japanese adults (≥18 years with CLBP-NeP of duration ≥3 months and severity ≥5 on a numerical rating scale (0= no pain, 10= worst possible pain. Treatment was 8 weeks with pregabalin (n=157 or usual care alone (n=174; choice of treatment was determined by the physician. The primary efficacy outcome was change from baseline to 8 weeks in pain-related interference with sleep, assessed using the Pain-Related Sleep Interference Scale (PRSIS; 0= did not interfere with sleep, 10= completely interferes with sleep. Secondary endpoints were changes in PRSIS at week 4, and changes at weeks 4 and 8 in pain (numerical rating scale, function (Roland-Morris Disability Questionnaire, and quality of life (EuroQol 5D-5L; global assessments of change were evaluated from the clinician and patient perspectives at the final visit. Results: Demographic characteristics were similar between cohorts, but clinical characteristics suggested greater disease severity in the pregabalin group including a higher mean (standard deviation pain score, 6.3 (1.2 versus 5.8 (1.1 (P<0.001. For the primary endpoint, pregabalin resulted in significantly greater improvements in PRSIS at week 8, least-squares mean changes of -1.3 versus

  8. Cost-effectiveness analysis of combination antifungal therapy with voriconazole and anidulafungin versus voriconazole monotherapy for primary treatment of invasive aspergillosis in Spain

    Directory of Open Access Journals (Sweden)

    Grau S

    2016-12-01

    Full Text Available Santiago Grau,1 Jose Ramon Azanza,2 Isabel Ruiz,3 Carlos Vallejo,4 Josep Mensa,5 Johan Maertens,6 Werner J Heinz,7 Jon Andoni Barrueta,8 Carmen Peral,9 Francisco Jesús Mesa,8 Miguel Barrado,10 Claudie Charbonneau,11 Darío Rubio-Rodríguez,12 Carlos Rubio-Terrés12 1Pharmacy Department, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, 2Clinical Pharmacology Department, Clínica Universidad de Navarra, Pamplona, 3Infectious Diseases Department, Hospital Universitari Vall d’Hebron, Barcelona, 4Hematology Department, Hospital Universitario Donostia, San Sebastián, 5Infectious Diseases Department, Hospital Clínic de Barcelona, Barcelona, Spain; 6Hematology Department, University Hospital Gasthuisberg, Leuven, Belgium; 7Hematology/Oncology Department, Medizinische Klinik und Poliklinik II, Universitätsklinikum, Würzburg, Germany; 8Medical Department, 9Economics and Outcomes Research Department, Pfizer S.L.U, Alcobendas, 10Clinical Trials Department, Trial Form Support, Madrid, Spain; 11Pharmacoeconomics Department, Pfizer International Operations, Paris, France; 12Pharmacoeconomics Department, Health Value, Madrid, Spain Objective: According to a recent randomized, double-blind clinical trial comparing the combination of voriconazole and anidulafungin (VOR+ANI with VOR monotherapy for invasive aspergillosis (IA in patients with hematologic disease or with hematopoietic stem cell transplant, mortality was lower after 6 weeks with VOR+ANI than with VOR monotherapy in a post hoc analysis of patients with galactomannan-based IA. The objective of this study was to compare the cost-effectiveness of VOR+ANI with VOR, from the perspective of hospitals in the Spanish National Health System.Methods: An economic model with deterministic and probabilistic analyses was used to determine costs per life-year gained (LYG for VOR+ANI versus VOR in patients with galactomannan-based IA. Mortality, adverse event rates, and life expectancy were

  9. Maraviroc (UK-427,857), a potent, orally bioavailable, and selective small-molecule inhibitor of chemokine receptor CCR5 with broad-spectrum anti-human immunodeficiency virus type 1 activity.

    Science.gov (United States)

    Dorr, Patrick; Westby, Mike; Dobbs, Susan; Griffin, Paul; Irvine, Becky; Macartney, Malcolm; Mori, Julie; Rickett, Graham; Smith-Burchnell, Caroline; Napier, Carolyn; Webster, Rob; Armour, Duncan; Price, David; Stammen, Blanda; Wood, Anthony; Perros, Manos

    2005-11-01

    Maraviroc (UK-427,857) is a selective CCR5 antagonist with potent anti-human immunodeficiency virus type 1 (HIV-1) activity and favorable pharmacological properties. Maraviroc is the product of a medicinal chemistry effort initiated following identification of an imidazopyridine CCR5 ligand from a high-throughput screen of the Pfizer compound file. Maraviroc demonstrated potent antiviral activity against all CCR5-tropic HIV-1 viruses tested, including 43 primary isolates from various clades and diverse geographic origin (geometric mean 90% inhibitory concentration of 2.0 nM). Maraviroc was active against 200 clinically derived HIV-1 envelope-recombinant pseudoviruses, 100 of which were derived from viruses resistant to existing drug classes. There was little difference in the sensitivity of the 200 viruses to maraviroc, as illustrated by the biological cutoff in this assay (= geometric mean plus two standard deviations [SD] of 1.7-fold). The mechanism of action of maraviroc was established using cell-based assays, where it blocked binding of viral envelope, gp120, to CCR5 to prevent the membrane fusion events necessary for viral entry. Maraviroc did not affect CCR5 cell surface levels or associated intracellular signaling, confirming it as a functional antagonist of CCR5. Maraviroc has no detectable in vitro cytotoxicity and is highly selective for CCR5, as confirmed against a wide range of receptors and enzymes, including the hERG ion channel (50% inhibitory concentration, >10 microM), indicating potential for an excellent clinical safety profile. Studies in preclinical in vitro and in vivo models predicted maraviroc to have human pharmacokinetics consistent with once- or twice-daily dosing following oral administration. Clinical trials are ongoing to further investigate the potential of using maraviroc for the treatment of HIV-1 infection and AIDS.

  10. [Fertility after treatment with Eazi-breedTM CIDR G for 6 or 12 days outside the breeding season in Lacaune dairy sheep].

    Science.gov (United States)

    Fleisch, A; Piechotta, M; Bollwein, H; Janett, F

    2013-07-01

    This study compares the fertility after short- and long-term synchronization using a progesterone intravaginal device in Lacaune dairy sheep outside the breeding season. For the experiment 108 Lacaune sheep were treated with Eazi-breed™ CIDR® G intravaginal devices (Pfizer Animal Health, Zürich) for 12 days (Group L, n = 60) or 6 days (Group K, n = 48) in combination with eCG (Group L) or with eCG and 125 μg Cloprostenol (Group K) at device removal. Thereafter the ewes were kept together with rams for 60 days, ewes in estrus were recorded and the fertility was assessed after lambing. Blood progesterone concentration was measured at device application, withdrawal and 14 days later. Results show that neither treatment nor parity had an influence on estrus rate (Group L 91.7 %, Group K 93.8 %, nulli- and pluriparous animals 96.9 % and 90.8 %, respectively). Group L showed a tendency towards a better first cycle lambing rate and a significantly (P sheep of Group K (71.7 % vs. 60.4 % and 83.3 % vs. 72.9 %). Pluriparous ewes had higher (P synchronized ewe than nulliparous sheep for the first cycle (75.0 % vs. 46.9 % and 1.4 ± 1.0 vs. 0.9 ± 1.1) as well as for the overall service period (92.1 % vs. 46.9 % and 1.7 ± 0.8 vs. 0.9 ± 1.1). Fourteen days after insert withdrawal progesterone concentrations were higher (P progesterone treatment and nulliparous ewes were less suitable for estrus induction outside the breeding season.

  11. Outlet strut fracture of Björk-Shiley convexo-concave valves: can valve-manufacturing characteristics explain the risk?

    Science.gov (United States)

    Omar, R Z; Morton, L S; Beirne, M; Blot, W J; Lawford, P V; Hose, R; Taylor, K M

    2001-06-01

    Björk-Shiley 60 degrees convexo-concave prosthetic heart valves (Shiley, Inc, Irvine, Calif, a subsidiary of Pfizer, Inc) continue to be a concern for approximately 35,000 nonexplanted patients worldwide, with approximately 600 events reported to the manufacturer to date. Fractures of the outlet struts of the valves began to appear in the early 1980s and have continued to the present, but their causes are only partially understood. A matched case-control study was conducted evaluating manufacturing records for 52 valves with outlet strut fractures and 248 control subjects matched for age at implantation, valve size, and valve position. In addition to the risk factors recognized as determinants of outlet strut fracture, the United Kingdom case-control study has observed 7- to 9-fold increased risk with performance of multiple hook deflection tests. This test was performed more than once, usually after rework on the valve. Six valves in this study underwent multiple hook deflection tests, of which 4 experienced an outlet strut fracture. Cracks and further rework were noted for these valves. Significant associations were also observed between outlet strut fracture and disc-to-strut gap measurements taken before the attachment of the sewing ring. It is our view that a combination of factors related to valve design, manufacturing process, and patient characteristics are responsible for outlet strut fractures of Björk-Shiley convexo-concave valves. Multiple hook deflection tests have emerged as a potential new risk factor for outlet strut fracture in both The Netherlands and the United Kingdom. This factor appears to be correlated with the presence of other abnormalities. A further study is needed to investigate the factors correlated with multiple hook deflection tests. On confirmation of risk, the presence of multiple hook deflection tests may be added to equations, quantifying the risk of outlet strut fracture for comparison against risk of mortality and serious

  12. Tiotropium and Salmeterol in COPD Patients at Risk of Exacerbations: A Post Hoc Analysis from POET-COPD(®).

    Science.gov (United States)

    Vogelmeier, Claus F; Asijee, Guus M; Kupas, Katrin; Beeh, Kai M

    2015-06-01

    Among patients with chronic obstructive pulmonary disease (COPD), the frequency and severity of past exacerbations potentiates future events. The impact of current therapies on exacerbation frequency and severity in patients with different exacerbation risks is not well known. A post hoc analysis of patients at low (≤1 exacerbation [oral steroids/antibiotics requirement] and no COPD-related hospitalization in the year preceding trial entry) or high (≥2 exacerbations [oral steroids/antibiotics requirement] or ≥1 COPD-related hospitalization[s] in the year preceding trial entry) exacerbation risk, from the Prevention of Exacerbations with Tiotropium in Chronic Obstructive Pulmonary Disease (POET-COPD(®)) database. Compared with salmeterol, tiotropium significantly increased time to first COPD exacerbation (hazard ratio 0.84; 95% confidence interval [CI] 0.76-0.92; p = 0.0002) and reduced the number of COPD exacerbations (rate ratio 0.90; 95% CI 0.81-0.99; p = 0.0383) in patients at high exacerbation risk. With treatment, the risk of remaining in the high-risk exacerbator subgroup was statistically lower with tiotropium versus salmeterol (risk ratio [RR] 0.89; 95% CI 0.80-1.00; p = 0.0478). For low-risk patients, time to first COPD exacerbation and number of COPD exacerbations were numerically lower with tiotropium versus salmeterol. With treatment, the risk of transitioning from a low to a high exacerbation risk was lower with tiotropium versus salmeterol (RR 0.87; 95% CI 0.71-1.07; p = 0.1968). This analysis confirms the higher efficacy of tiotropium versus salmeterol in prolonging time to first COPD exacerbation and reducing number of exacerbations in patients both at low and high exacerbation risk. Boehringer Ingelheim and Pfizer. ClinicalTrials.gov NCT00563381.

  13. Annual biologic treatment cost for new and existing patients with moderate to severe plaque psoriasis in Greece

    Directory of Open Access Journals (Sweden)

    Fragoulakis V

    2015-01-01

    Full Text Available Vassilis Fragoulakis,1 Efklidis Raptis,2 Elli Vitsou,2 Nikolaos Maniadakis1 1Health Services Organization and Management, National School of Public Health, 2Pfizer Hellas, Athens, Greece Aim: The aim of the present study was to estimate the annual per-patient cost of treatment with adalimumab, etanercept, infliximab, and ustekinumab by response status for new and existing patients with moderate to severe psoriasis in Greece. Methods: An economic analysis was developed from a national health care perspective to estimate the direct cost of treatment alternatives for new and existing patients within a 1-year time horizon. The model included drug acquisition and administration costs for responders and nonresponders. Real-world treatment pattern and resource use data were extracted through nationwide field research using telephone-based interviews with a representative sample of dermatologists. Unit costs were collected from official sources in the public domain. Results: The mean annual cost of treatment for new patients who responded (or did not respond to treatment was as follows: adalimumab €10,686 (€3,821, etanercept €10,415 (€3,224, infliximab €14,738 (€7,582, and ustekinumab €17,155 (€9,806. For existing patients the mean annual cost was €9,916, €9,462, €12,949, and €17,149, respectively. Results did not change significantly under several one-way sensitivity and scenario analyses. Conclusion: Under the base-case scenario, the cost of treatment with etanercept is lower than that of the other biological agents licensed for moderate to severe plaque psoriasis in Greece, for both new and existing patients, irrespective of response status. Keywords: adalimumab, etanercept, infliximab, ustekinumab, economic evaluation, biologics

  14. Estimated Budget Impact of Adopting the Affordable Care Act's Required Smoking Cessation Coverage on United States Healthcare Payers.

    Science.gov (United States)

    Baker, Christine L; Ferrufino, Cheryl P; Bruno, Marianna; Kowal, Stacey

    2017-01-01

    on health plan's budgets. Pfizer Inc.

  15. Maintenance of Remission with Etanercept-DMARD Combination Therapy Compared with DMARDs Alone in African and Middle Eastern Patients with Active Rheumatoid Arthritis.

    Science.gov (United States)

    Bassiouni, Hassan; Spargo, Catherine Elizabeth; Vlahos, Bonnie; Jones, Heather E; Pedersen, Ron; Shirazy, Khalid

    2018-06-01

    To compare etanercept (ETN) and placebo (PBO) for maintaining low disease activity (LDA) achieved with ETN in patients with rheumatoid arthritis (RA) from Africa and the Middle East. In this subset analysis of the Treat-to-Target trial (ClinicalTrials.gov identifier NCT01981473), 53 adult patients with moderate-to-severe RA nonresponsive to methotrexate were treated with 50 mg ETN/week for 24 weeks (Period 1). Patients achieving LDA were randomized to continue ETN treatment or switched to PBO for an additional 28 weeks (Period 2). The proportion of patients maintaining LDA or remission in each arm at the end of Period 2 was determined. Additional efficacy and patient-reported outcomes (PROs) were also evaluated. During Period 1, 51 patients achieved LDA according to the disease activity score-28 joints-erythrocyte sedimentation rate (DAS28-ESR LDA) and 30 achieved remission. At week 52, nine of 22 and eight of 29 in the ETN and PBO groups, respectively, remained in DAS28-ESR LDA without experiencing a flare. Additionally, six of 14 and five of 16 in the ETN and PBO groups, respectively, remained in remission. Among patients experiencing a flare during Period 2, 13 of 22 and 21 of 29 received ETN or PBO, respectively. The median time to flare was 193 and 87 days in the ETN and PBO groups, respectively. At week 52, consistently more patients in the ETN group than in the PBO group achieved predetermined efficacy and PRO endpoints. These data suggest continuing ETN maintenance therapy is beneficial to patients after they have achieved their treatment target. However, this subset analysis is limited by the small patient population and must be interpreted with caution. Pfizer. ClinicalTrials.gov identifier, NCT0198147.

  16. Sequences within both the 5' UTR and Gag are required for optimal in vivo packaging and propagation of mouse mammary tumor virus (MMTV genomic RNA.

    Directory of Open Access Journals (Sweden)

    Farah Mustafa

    Full Text Available BACKGROUND: This study mapped regions of genomic RNA (gRNA important for packaging and propagation of mouse mammary tumor virus (MMTV. MMTV is a type B betaretrovirus which preassembles intracellularly, a phenomenon distinct from retroviruses that assemble the progeny virion at cell surface just before budding such as the type C human and feline immunodeficiency viruses (HIV and FIV. Studies of FIV and Mason-Pfizer monkey virus (MPMV, a type D betaretrovirus with similar intracellular virion assembly processes as MMTV, have shown that the 5' untranslated region (5' UTR and 5' end of gag constitute important packaging determinants for gRNA. METHODOLOGY: Three series of MMTV transfer vectors containing incremental amounts of gag or 5' UTR sequences, or incremental amounts of 5' UTR in the presence of 400 nucleotides (nt of gag were constructed to delineate the extent of 5' sequences that may be involved in MMTV gRNA packaging. Real time PCR measured the packaging efficiency of these vector RNAs into MMTV particles generated by co-transfection of MMTV Gag/Pol, vesicular stomatitis virus envelope glycoprotein (VSV-G Env, and individual transfer vectors into human 293T cells. Transfer vector RNA propagation was monitored by measuring transduction of target HeLaT4 cells following infection with viral particles containing a hygromycin resistance gene expression cassette on the packaged RNA. PRINCIPAL FINDINGS: MMTV requires the entire 5' UTR and a minimum of ~120 nucleotide (nt at the 5' end of gag for not only efficient gRNA packaging but also propagation of MMTV-based transfer vector RNAs. Vector RNAs without the entire 5' UTR were defective for both efficient packaging and propagation into target cells. CONCLUSIONS/SIGNIFICANCE: These results reveal that the 5' end of MMTV genome is critical for both gRNA packaging and propagation, unlike the recently delineated FIV and MPMV packaging determinants that have been shown to be of bipartite nature.

  17. Multiple roles and therapeutic implications of Akt signaling in cancer

    Directory of Open Access Journals (Sweden)

    Emiliano Calvo

    2009-06-01

    Full Text Available Emiliano Calvo1, Victoria Bolós2, Enrique Grande21Centro Integral Oncológico Clara Campal (CiOCC, Madrid. Spain; 2Pfizer Oncology, Alcobendas-Madrid, SpainAbstract: The prominence of the PI3K-Akt signaling pathway in several tumors indicates a relationship with tumor grade and proliferation. Critical cellular processes are driven through this pathway. More detailed knowledge of the pathogenesis of tumors would enable us to design targeted drugs to block both membrane tyrosine kinase receptors and the intracellular kinases involved in the transmission of the signal. The newly approved molecular inhibitors sunitinib (an inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and other tyrosine kinase receptors, sorafenib (a serine–threonine kinase inhibitor that acts against B-Raf and temsirolimus (an mTOR inhibitor shown clinical activity in advanced kidney cancer. Chronic myeloid leukemia has changed its natural history thanks to imatinib and dasatinib, both of which inhibit the intracellular bcr/abl protein derived from the alteration in the Philadelphia chromosome. Intracellular pathways are still important in cancer development and their blockade directly affects outcome. Cross-talk has been observed but is not well understood. Vertical and horizontal pathway blockade are promising anticancer strategies. Indeed, preclinical and early clinical data suggest that combining superficial and intracellular blocking agents can synergize and leverage single-agent activity. The implication of the Akt signaling pathway in cancer is well established and has led to the development of new anticancer agents that block its activation.Keywords: Akt, cancer, therapeutic target, Akt inhibitors

  18. Living with fibromyalgia: results from the functioning with fibro survey highlight patients' experiences and relationships with health care providers

    Directory of Open Access Journals (Sweden)

    Golden A

    2015-11-01

    Full Text Available Angela Golden,1 Yvonne D'Arcy,2 Elizabeth T Masters,3 Andrew Clair3 1NP from Home, LLC, Munds Park, AZ, 2Pain Management and Palliative Care, Suburban Hospital-Johns Hopkins Medicine, Bethesda, MD, 3Pfizer, New York, NY, USA Abstract: Fibromyalgia (FM is a chronic disorder characterized by widespread pain, which can limit patients' physical function and daily activities. FM can be challenging to treat, and the treatment approach could benefit from a greater understanding of patients' perspectives on their condition and their care. Patients with FM participated in an online survey conducted in the USA that sought to identify the symptoms that had the greatest impact on patients' daily lives. The purpose of the survey was to facilitate efforts toward improving care of patients by nurse practitioners, primary care providers, and specialists, in addition to contributing to the development of new outcome measures in both clinical trials and general practice. A total of 1,228 patients with FM completed the survey, responding to specific questions pertaining to symptoms, impact of symptoms, management of FM, and the relationship with health care providers. Chronic pain was identified as the key FM symptom, affecting personal and professional relationships, and restricting physical activity, work, and social commitments. Patients felt that the severity of their condition was underestimated by family, friends, and health care providers. The results of this survey highlight the need for nurse practitioners, primary care providers, and specialists to provide understanding and support to patients as they work together to enable effective diagnosis and management of FM. Keywords: fibromyalgia, pain, survey, impact, support

  19. Superovulation and embryo production in tropical adapted Bos taurus (Caracu and Bos indicus (Nelore cows

    Directory of Open Access Journals (Sweden)

    Rafael Herrera Alvarez

    2011-01-01

    Full Text Available The aim of this study was to compare ovarian response and embryo production of superovulated Bos indicus and Bos taurus cows adapted to the environmental conditions from São Paulo State, Brazil. Ninety non-lactating cows from Caracu ( Bos taurus, n=40 and Nelore (Bos indicus, n=50 were treated with an intravaginal device containing progesterone (1.38 mg; CIDRB ®, Pfizer Animal Health, Montreal, Québec, Canada and 2.5 mg, intramuscularly (IM, of estradiol benzoate (Estrogin®, Farmavet, São Paulo, Brazil. Four days later, all animals were treated with multiple IM injections of 400 IU of FSH (Pluset®, Calier, Spain in decreasing doses (75–75; 75–50; 50–25, and 25–25 IU at 12-h intervals over 4 days. On the seventh day, CIDR-B device was removed and cows received, IM, 150 ìg of cloprostenol (Veteglan®, Calier, Spain. Cows were then inseminated 48 and 62 h after cloprostenol treatment and embryos were recovered non-surgically seven days after first insemination. Differences in the number of corpora lutea (CL number, total number of structures (ova/embryos, and number of transferable embryos were analyzed by Student t test. There was no difference (P > 0.05 in the average number of CL, total ova/embryos and transferable embryos of Caracu (11.4 ± 3.3; 8.6 ± 2.6 e 6.0 ± 2.4 and Nelore (12.0 ± 4.1; 9.0 ± 4.3 e 5.1 ± 2.9 cows, respectively. These results suggest that Caracu and Nelore cows superovulated in tropical climate had similar ovarian responses and embryo production.

  20. Calcium channel blockers, angiotensin receptor blockers, and angiotensin-converting enzyme inhibitors: Effectiveness in combination with diuretics or β-blockers for treating hypertension

    Directory of Open Access Journals (Sweden)

    John D Bisognano

    2007-11-01

    Full Text Available John D Bisognano1, Trent McLaughlin2, Craig S Roberts3, Simon SK Tang31Internal Medicine Department, Cardiology Division, the University of Rochester Medical Center, Rochester, NY, USA; 2NDC Health, Phoenix, Arizona, USA; 3Pfizer Inc, New York, NY, USAAbstract: This retrospective database analysis compared the effectiveness of dihydropyridine calcium channel blockers (DHPs, angiotensin-converting enzyme (ACE inhibitors, and angiotensin receptor blockers (ARBs added to diuretics or β-blockers. Adults with hypertension treated with diuretic or β-blocker monotherapy between 1998 and 2001 were identified from a large US electronic medical records database of primary care practices. Patients were required to have a baseline blood pressure (BP ≥140/90 mmHg (≥130/80 mmHg for diabetes mellitus and recorded BP measurements within 6 months before and 1–12 months following index date. Patients were matched 1:1:1 by propensity score to correct for differences in baseline characteristics. 1875 patients met study criteria and 660 (220 in each cohort were matched based on propensity scores. Matched cohorts had no significant differences in baseline characteristics. Mean changes in systolic/diastolic BP were –17.5/–8.8, –15.7/–6.3, and –13.0/–8.0 mmHg with DHPs, ACE inhibitors, and ARBs, respectively. Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High BP 6/7 goal attainment for each regimen was 47.3%, 40.0%, and 32.2%, respectively. DHPs, ACE inhibitors, and ARBs improved BP when added to patients’ β-blocker or diuretic therapy. The greatest benefits were observed with DHPs, followed by ACE inhibitors, then ARBs.Keywords: hypertension, amlodipine besylate, lisinopril, valsartan, Joint National Committee (JNC 6 and 7

  1. Dose Titration of Pregabalin in Patients with Painful Diabetic Peripheral Neuropathy: Simulation Based on Observational Study Patients Enriched with Data from Randomized Studies.

    Science.gov (United States)

    Alexander, Joe; Edwards, Roger A; Manca, Luigi; Grugni, Roberto; Bonfanti, Gianluca; Emir, Birol; Whalen, Edward; Watt, Stephen; Parsons, Bruce

    2018-03-01

    Achieving a therapeutic response to pregabalin in patients with painful diabetic peripheral neuropathy (pDPN) requires adequate upward dose titration. Our goal was to identify relationships between titration and response to pregabalin in patients with pDPN. Data were integrated from nine randomized, placebo-controlled clinical trials as well as one 6-week open-label observational study conducted by 5808 physicians (2642 patients with pDPN) in standard outpatient settings in Germany. These studies evaluated pregabalin for treatment of pDPN. Using these data, we examined "what if" scenarios using a microsimulation platform that integrates data from randomized and observational sources as well as autoregressive-moving-average with exogenous inputs models that predict pain outcomes, taking into account weekly changes in pain, sleep interference, dose, and other patient characteristics that were unchanging. Final pain levels were significantly different depending on dose changes (P titration regardless of baseline pain severity. Altogether, 78.5% of patients with pDPN had 0-1 dose change, and 15.2% had ≥ 2 dose changes. Simulation demonstrated that the 4.8% of inadequately titrated patients who did not improve/very much improve their pain levels would have benefited from ≥ 2 dose changes. Patient satisfaction with tolerability (range 90.3-96.2%) was similar, regardless of baseline pain severity, number of titrations, or extent of improvement, suggesting that tolerability did not influence treatment response patterns. Upward dose titration reduced pain in patients with pDPN who actually received it. Simulation also predicted pain reduction in an inadequately titrated nonresponder subgroup of patients had they actually received adequate titration. The decision not to uptitrate must have been driven by factors other than tolerability. Pfizer, Inc.

  2. Safety and immunogenicity of a CRM or TT conjugated meningococcal vaccine in healthy toddlers.

    Science.gov (United States)

    Bona, Gianni; Castiglia, Paolo; Zoppi, Giorgio; de Martino, Maurizio; Tasciotti, Annaelisa; D'Agostino, Diego; Han, Linda; Smolenov, Igor

    2016-06-17

    MenACWY-CRM (Menveo(®); GlaxoSmithKline) and MenACWY-TT (Nimenrix(®); Pfizer) are two meningococcal vaccines licensed in the European Union for use in both children and adults. While both vaccines target meningococcal serogroups A, C, W and Y, immunogenicity and reactogenicity of these quadrivalent meningococcal conjugate vaccines may differ due to differences in formulation processes and chemical structure. Yet data on the comparability of these two vaccines are limited. The reactogenicity and immunogenicity of one dose of either MenACWY-CRM or MenACWY-TT were evaluated in healthy toddlers aged 12-15 months. Immunogenicity was assessed using serum bactericidal antibody assays (SBA) with human (hSBA) and rabbit (rSBA) complement. A total of 202 children aged 12-15 months were enrolled to receive one dose of MenACWY-CRM or MenACWY-TT. Similar numbers of subjects reported solicited reactions within 7 days following either vaccination. Tenderness at the injection site was the most common local reaction. Systemic reactions reported were similar for both vaccines and mostly mild to moderate in severity: irritability, sleepiness and change in eating habits were most commonly reported. Immunogenicity at 1 month post-vaccination was generally comparable for both vaccines across serogroups. At 6 months post-vaccination antibody persistence against serogroups C, W, and Y was substantial for both vaccines, as measured by both assay methodologies. For serogroup A, hSBA titers declined in both groups, while rSBA titers remained high. Despite differences in composition, the MenACWY-CRM and MenACWY-TT vaccines have comparable reactogenicity and immunogenicity profiles. Immediate immune responses and short-term antibody persistence were largely similar between groups. Both vaccines were well-tolerated and no safety concerns were identified. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. A combined marker of inflammation in individuals with mania.

    Directory of Open Access Journals (Sweden)

    Faith Dickerson

    Full Text Available BACKGROUND: Markers of immune activation have been associated with mania but have not been examined in combination. We studied the association between mania and an inflammation score based on four immune markers. METHODS: A total of 57 individuals with mania were assessed at up to three time points: the day of hospital admission, evaluation several days later, and six-month follow-up. Also assessed were 207 non-psychiatric controls and 330 individuals with recent onset psychosis, multi-episode schizophrenia, or bipolar disorder depression. A combined inflammation score was calculated by factor analysis of the levels of class-specific antibodies to the NR peptide of the NMDA receptor; gliadin; Mason-Pfizer monkey virus protein 24; and Toxoplasma gondii. Inflammation scores among groups were compared by multivariate analyses. The inflammation score of the mania group at evaluation was studied as a predictor of re-hospitalization in the follow-up period. RESULTS: The combined inflammation score of the mania group at hospital admission and at evaluation differed significantly from that of the non-psychiatric controls (t=3.95, 4.10, p<.001. The inflammation score was significantly decreased at six month follow-up (F=5.85, p=0.004. There were not any significant differences in the inflammation scores of any of the other psychiatric groups and that of the controls. Within the mania group, an elevated inflammation score at evaluation predicted re-hospitalization (Hazard ratio=7.12, p=.005. CONCLUSIONS: Hospitalization for mania is associated with immune activation. The level of this activation is predictive of subsequent re-hospitalization. Interventions for the modulation of inflammation should be evaluated for the therapy of individuals with mania.

  4. Relative Risks of Contributing Factors to Morbidity and Mortality in Adults With Craniopharyngioma on Growth Hormone Replacement.

    Science.gov (United States)

    Yuen, Kevin C J; Mattsson, Anders F; Burman, Pia; Erfurth, Eva-Marie; Camacho-Hubner, Cecilia; Fox, Janet L; Verhelst, Johan; Geffner, Mitchell E; Abs, Roger

    2018-02-01

    In adults, craniopharyngioma (CP) of either childhood-onset (CO-CP) or adult-onset (AO-CP) is associated with increased morbidity and mortality, but data on the relative risks (RRs) of contributing factors are lacking. To assess the RRs of factors contributing to morbidity and mortality in adults with CO-CP and AO-CP. Data on 1669 patients with CP from KIMS (Pfizer International Metabolic Database) were analyzed using univariate and multiple Poisson and Cox regression methods. When CO-CP and AO-CP groups were combined, history of stroke and hyperlipidemia increased cardiovascular risk, higher body mass index (BMI) and radiotherapy increased cerebrovascular risk, and increased waist circumference increased the risk of developing diabetes mellitus (DM). Compared with patients with CO-CP, patients with AO-CP had a threefold higher risk of tumor recurrence, whereas being female and previous radiotherapy exposure conferred lower risks. Radiotherapy and older age with every 10 years from disease onset conferred a 2.3- to 3.5-fold risk for developing new intracranial tumors, whereas older age, greater and/or increasing BMI, history of stroke, and lower insulinlike growth factor I (IGF-I) standard deviation score measured at last sampling before death were related to increased all-cause mortality. Compared with the general population, adults with CP had 9.3-, 8.1-, and 2.2-fold risks of developing DM, new intracranial tumors, and early death, respectively. Conventional factors that increase the risks of cardio- and cerebrovascular diseases and DM and risks for developing new intracranial tumors contributed to excess morbidity and mortality. In addition, lower serum IGF-I level measured from the last sample before death was inversely associated with mortality risk in patients with CP. Copyright © 2017 Endocrine Society

  5. Effects of two eye drop products on computer users with subjective ocular discomfort.

    Science.gov (United States)

    Skilling, Francis C; Weaver, Tony A; Kato, Kenneth P; Ford, Jerry G; Dussia, Elyse M

    2005-01-01

    An increasing number of people seek medical attention for symptoms of visual discomfort due to computer vision syndrome (CVS). We compared the efficacy and adverse event rates of a new eye lubricant, OptiZen (InnoZen, Inc., polysorbate 80 0.5%) and Visine Original (Pfizer Consumer Healthcare, tetrahydrozoline HCl 0.05%). In this double-blind parallel arm trial, 50 healthy men and women, ages 18 to 65 years, with symptoms of CVS who use a video display terminal for a minimum of 4 hours per day were randomized to OptiZen (n = 25) or Visine Original (n= 25), 1 to 2 drops b.i.d. for 5 days. The primary end-points were ocular discomfort and adverse events. OptiZen and Visine Original had similar efficacy in alleviating symptoms of ocular discomfort (odds ratio of 1.23 [95% confidence interval, 0.63 to 2.42], P= 0.55). OptiZen and Visine Original were very similar with respect to odds ratios and 95% confidence interval (CI) for each of the measurement times (P= 0.72). Visine Original users reported a significantly higher incidence of temporary ocular stinging/burning immediately after drug instillation (28%, 7/25) than did OptiZen users (4%, 1/24) (P= 0.05). Patients using OptiZen were 89% less likely to have stinging/burning effects than those patients using Visine Original (95% CI: 0.01 to 0.95). OptiZen and Visine Original are effective at alleviating ocular discomfort associated with prolonged computer use. Adverse event findings suggest that OptiZen causes less ocular discomfort on instillation, potentially attributable to its milder ingredient profile.

  6. Novel engineered HIV-1 East African Clade-A gp160 plasmid construct induces strong humoral and cell-mediated immune responses in vivo

    International Nuclear Information System (INIS)

    Muthumani, Karuppiah; Zhang Donghui; Dayes, Nathanael S.; Hwang, Daniel S.; Calarota, Sandra A.; Choo, Andrew Y.; Boyer, Jean D.; Weiner, David B.

    2003-01-01

    HIV-1 sequences are highly diverse due to the inaccuracy of the viral reverse transcriptase. This diversity has been studied and used to categorize HIV isolates into subtypes or clades, which are geographically distinct. To develop effective vaccines against HIV-1, immunogens representing different subtypes may be important for induction of cross-protective immunity, but little data exist describing and comparing the immunogenicity induced by different subtype-based vaccines. This issue is further complicated by poor expression of HIV structural antigens due to rev dependence. One costly approach is to codon optimize each subtype construct to be examined. Interestingly, cis-acting transcriptional elements (CTE) can also by pass rev restriction by a rev independent export pathway. We reasoned that rev+CTE constructs might have advantages for such expression studies. A subtype A envelope sequence from a viral isolate from east Africa was cloned into a eukaryotic expression vector under the control of the CMV-IE promoter. The utility of inclusion of the Mason-Pfizer monkey virus (MPV)-CTE with/without rev for driving envelope expression and immunogenicity was examined. Expression of envelope (gp120) was confirmed by immunoblot analysis and by pseudotype virus infectivity assays. The presence of rev and the CTE together increased envelope expression and viral infection. Furthermore the CTE+rev construct was significantly more immunogenic then CTE alone vector. Isotype analysis and cytokine profiles showed strong Th1 response in plasmid-immunized mice, which also demonstrated the superior nature of the rev+CTE construct. These responses were of similar or greater magnitude to a codon-optimized construct. The resulting cellular immune responses were highly cross-reactive with a HIV-1 envelope subtype B antigen. This study suggests a simple strategy for improving the expression and immunogenicity of HIV subtype-specific envelope antigens as plasmid or vector

  7. Effect of sildenafil citrate on secondary healing in full thickness skin defects in experiment.

    Science.gov (United States)

    Cakmak, E; Karasoy Yesilada, A; Sevim, K Z; Sumer, O; Tatlidede, H S; Sakiz, D

    2014-01-01

    An acceleration of the wound healing process expedites chronic wound patient's return to normal social environments significantly. Sildenafil, a cyclic guanosine monophosphate (cGMP)-dependent phosphodiesterase- 5 inhibitor has been shown to be a potent stimulator of angiogenesis through upregulation of cGMP. In our study, sildenafil was administered orally as a cost-effective supplement in the treatment of full thickness defects and chronic wounds in that manner with low incidence of side effects and morbidity. Randomly selected 72 Wistar-Albino rats were divided into the two groups, 36 rats in each group. Control group (n =36) was divided further into a secondary healing group consisting of 9 rats and a pathology group consisting of 27 rats (pathology group 1: 9 rats, 4th and 7th day of wound healing, pathology group 2: 9 rats, 10th and 14th day of wound healing, pathology group 3: 9 rats, 21st and 28th day of wound healing. Experimental group consisted of 36 rats which received sildenafil citrate (Viagra® Pfizer, Germany) for secondary wound healing to proceed. The average wound healing period in the control group was 17.89 days and in the sildenafil citrate administered group 14.56 days. The difference of the epithelialisation on full thickness defects were more prominent on days 5 and 11 postoperatively. In the sildenafil citrate applied group, on the 7th day, the defect was 25% smaller and on the 13th day, the defect contracted by 38%. In conclusion, we believe that sildenafil citrate administered orally is a cost- effective supplement in the treatment of full thickness defects and chronic wounds in that manner with low incidence of side effects and morbidity (Tab. 4, Fig. 7, Ref. 34).

  8. Effect of sildenafil citrate (Viagra®) on trace element concentration in serum and brain of rats.

    Science.gov (United States)

    Fayed, Abdel-Hasseb A; Gad, Shereen B

    2011-12-01

    As a vasodilator with good hemodynamic effects, sildenafil has been successfully used in the treatment of patients with pulmonary hypertension and cardiovascular diseases. By selectively inhibiting phosphodiestrase type 5 (PDE-5) and thus effectively reducing the breakdown of c GMP, sildenafil administration can markedly improve the erectile dysfunction. Sildenafil also elevates localized cerebral blood flow in rat brain. The objective of the present study was to investigate the effect of sildenafil on the level of trace elements (Zinc (Zn), copper (Cu), iron (Fe), selenium (Se), cobalt (Co), and chromium (Cr)) in blood and brain of rats. Sixteen male albino rats weighing 180-200 g were divided into two groups (8 rats/group). Sildenafil (Viagra, Pfizer Inc.) was dissolved in saline and administered at a dose of 10mg/kg i.p. (0.5 ml volume) to rats in the treated group every 72 h for 12 injections. Rats in the control group were administered the same volume of saline as in treated group. All rats were sacrificed 24h after the last injection. Blood samples were collected and serum was separated and stored at -20°C. Brains were dissected and stored frozen until analysis. Trace elements concentrations were determined by flame emission atomic absorption spectrophotometer. Results showed that sildenafil injection significantly (P<0.05) increased serum and brain Se and Cu concentrations. Moreover, sildenafil increased the Cr concentration in the brain tissue. It was concluded that sildenafil citrate administration increased serum Se and Cu as well as, increased brain Se, Cu, and Cr concentrations in rats. Copyright © 2011 Elsevier GmbH. All rights reserved.

  9. Bioequivalence of 2 Formulations of Sildenafil Oral Soluble Film 100 mg and Sildenafil Citrate (Viagra) 100 mg Oral Tablets in Healthy Male Volunteers.

    Science.gov (United States)

    Dadey, Eric

    Sildenafil citrate tablets (VIAGRA; Pfizer Inc) have been used since 1998 as an oral therapy for the treatment of erectile dysfunction. However, in some cases, patients may have difficulty in swallowing tablets, and the need to use water to aid in the oral administration of the tablets has the potential to interrupt the sexual encounter, reduce spontaneity, and therefore decrease the quality of the experience. Two oral soluble film (OSF) formulations of sildenafil were developed using MonoSol Rx's proprietary PharmFilm technology. Both films were formulated to dissolve rapidly on the tongue, thereby releasing the drug into the oral cavity, whereupon it is swallowed without the use of water. From a patient perspective, it is anticipated that the film formulations of sildenafil citrate will provide a more compliant and discreet dosage form. The purpose of this clinical study was to compare the bioequivalence of the 2 sildenafil OSF 100 mg formulations (MonoSol Rx, LLC) with the sildenafil citrate 100 mg tablets. The design was a single-dose, randomized, open-label, 3-period, 6-sequence, 3-treatment, single-center, crossover study conducted in 18 healthy, nonsmoking male volunteers under fasting conditions, with each treatment period separated by a 7-day washout period. Plasma sildenafil concentrations were measured predose and then periodically to 24 hours after dosing. The 90% confidence intervals for plasma sildenafil AUC0-t, AUC0-∞, and Cmax for both sildenafil OSF formulations as compared with sildenafil citrate tablets were all within the 80%-125% range, indicating bioequivalence of both film formulations to sildenafil citrate tablets. Overall, the demonstrated bioequivalence coupled with the performance advantages of an OSF dosage form (ie, rapid dissolution in the mouth, can be taken without water, and can be dosed discreetly) suggest that the sildenafil OSF may provide an attractive alternative to sildenafil citrate oral tablets.

  10. Metabolic profiling of follistatin overexpression: a novel therapeutic strategy for metabolic diseases

    Directory of Open Access Journals (Sweden)

    Singh R

    2018-03-01

    Full Text Available Rajan Singh,1,2 Shehla Pervin,1,2 Se-Jin Lee,3,4 Alan Kuo,5 Victor Grijalva,6 John David,7 Laurent Vergnes,8 Srinivasa T Reddy1,6 1Department of Obstetrics and Gynecology, UCLA School of Medicine, Los Angeles, CA, USA; 2Division of Endocrinology and Metabolism, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA; 3The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA; 4Department of Genetics and Genome Sciences, University of Connecticut School of Medicine, CT, USA; 5Department of Biology, California State University Dominguez Hills, CA, USA; 6Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, CA, USA; 7Department of Comparative Medicine, Pfizer Inc, San Diego, CA, USA; 8Department of Human Genetics, UCLA School of Medicine, Los Angeles, CA, USA Background: Follistatin (Fst promotes brown adipocyte characteristics in adipose tissues.Methods: Abdominal fat volume (CT scan, glucose clearance (GTT test, and metabolomics analysis (mass spectrometry of adipose tissues from Fst transgenic (Fst-Tg and wild type (WT control mice were analyzed. Oxygen consumption (Seahorse Analyzer and lipidomics (gas chromatography was analyzed in 3T3-L1 cells.Results: Fst-Tg mice show significant decrease in abdominal fat content, increased glucose clearance, improved plasma lipid profiles and significant changes in several conventional metabolites compared to the WT mice. Furthermore, overexpression of Fst in 3T3-L1 cells resulted in up regulation of key brown/beige markers and changes in lipidomics profiles. Conclusion: Fst modulates key factors involved in promoting metabolic syndrome and could be used for therapeutic intervention. Keywords: follistatin, transgenic, adipocyte, fibroblast growth factor 21, AdipoQ

  11. Positive Effectiveness of Tafamidis in Delaying Disease Progression in Transthyretin Familial Amyloid Polyneuropathy up to 2 Years: An Analysis from the Transthyretin Amyloidosis Outcomes Survey (THAOS).

    Science.gov (United States)

    Mundayat, Rajiv; Stewart, Michelle; Alvir, Jose; Short, Sarah; Ong, Moh-Lim; Keohane, Denis; Rill, Denise; Sultan, Marla B

    2018-04-09

    The effectiveness of tafamidis for the treatment of transthyretin familial amyloid polyneuropathy (TTR-FAP) was evaluated using data from the Transthyretin Amyloidosis Outcomes Survey (THAOS) registry. Subjects receiving tafamidis (n = 252) were compared with untreated subjects in a non-randomized, matched cohort analysis. Subjects were matched with up to four untreated controls by genetic mutation, region of birth, and mean treatment propensity score. The matched, treated sample consisted predominantly of subjects with the Val30Met genotype (92.5%), from Portugal, and with a mean age of 40.4 years. Over the course of the 2-year follow-up period, subjects treated with tafamidis showed significantly less deterioration on the Neuropathy Impairment Score for Lower Limbs (p < 0.001) and its subscales (p < 0.023) compared with untreated subjects. There was significantly less deterioration among tafamidis-treated subjects compared with untreated subjects on the Norfolk Quality of Life scale (p < 0.001). There were no significant differences observed in functional (assessed by Karnofsky Performance Status Scale score) or nutritional (assessed by modified body mass index) status between the treated and untreated groups. The primary model which examined survival from baseline using the matched cohort was not able to yield estimates of the hazard ratio, as there were no deaths in the tafamidis-treated subjects. These findings support the results from clinical trials and strengthen evidence of the effectiveness of tafamidis beyond conventional clinical trials. ClinicalTrials.gov: NCT00628745 FUNDING: Pfizer.

  12. Adverse drug reactions and drug–drug interactions with over-the-counter NSAIDs

    Directory of Open Access Journals (Sweden)

    Moore N

    2015-07-01

    Full Text Available Nicholas Moore,1 Charles Pollack,2 Paul Butkerait2 1Department of Pharmacology, Université de Bordeaux, Bordeaux, France; 2Pfizer Consumer Healthcare, Madison, NJ, USA Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs such as ibuprofen have a long history of safe and effective use as both prescription and over-the-counter (OTC analgesics/antipyretics. The mechanism of action of all NSAIDs is through reversible inhibition of cyclooxygenase enzymes. Adverse drug reactions (ADRs including gastrointestinal bleeding as well as cardiovascular and renal effects have been reported with NSAID use. In many cases, ADRs may occur because of drug–drug interactions (DDIs between the NSAID and a concomitant medication. For example, DDIs have been reported when NSAIDs are coadministered with aspirin, alcohol, some antihypertensives, antidepressants, and other commonly used medications. Because of the pharmacologic nature of these interactions, there is a continuum of risk in that the potential for an ADR is dependent on total drug exposure. Therefore, consideration of dose and duration of NSAID use, as well as the type or class of comedication administered, is important when assessing potential risk for ADRs. Safety findings from clinical studies evaluating prescription-strength NSAIDs may not be directly applicable to OTC dosing. Health care providers can be instrumental in educating patients that using OTC NSAIDs at the lowest effective dose for the shortest required duration is vital to balancing efficacy and safety. This review discusses some of the most clinically relevant DDIs reported with NSAIDs based on major sites of ADRs and classes of medication, with a focus on OTC ibuprofen, for which the most data are available. Keywords: adverse effects, nonsteroidal anti-inflammatory drugs, gastrointestinal, cardiovascular, renal

  13. A randomized controlled trial comparing mupirocin versus Polysporin Triple for the prevention of catheter-related infections in peritoneal dialysis patients (the MP3 study).

    Science.gov (United States)

    Jassal, Sarbjit V; Lok, Charmaine E

    2008-01-01

    Peritonitis remains the most serious complication of peritoneal dialysis (PD). Gram-positive organisms are among the most common causes of PD peritonitis; however, recent trends show increasing rates of gram-negative and fungal infections. Strategies to prevent peritonitis include the use of prophylactic topical mupirocin at the site where the PD catheter exits from the abdominal wall; however, mupirocin does not afford protection against gram-negative or fungal infections. The aim of this study is to determine if the incidence of catheter-related infections (exit-site infection, tunnel infection, or peritonitis) is significantly reduced by the routine application of Polysporin Triple antibiotic ointment (Pfizer Canada, Markham, Ontario, Canada) in comparison to mupirocin ointment. The Mupirocin Versus Polysporin Triple Study (MP3) is a multicenter, randomized, double-blinded controlled study comparing Polysporin Triple (P3) against the current standard of care. The aim of the study is to recruit 200 patients being treated with or starting on PD and randomize them to receive either mupirocin or P3 at the catheter exit site. Patients will be followed for 18 months or until death or transfer from PD to an alternate treatment modality. The primary outcome will be the time to first catheter-related infection. Catheter-related infections will be strictly defined using current guidelines and categorized into exit-site infections, infective peritonitis, or tunnel infections. The primary analysis will be an intention-to-treat analysis. The results of this study will help determine if the use of P3 is superior to mupirocin ointment in the prevention of catheter-related infections and will help guide evidence-based best practices.

  14. Supplementation with rumen-protected L-arginine-HCl increased fertility in sheep with synchronized estrus.

    Science.gov (United States)

    de Chávez, Julio Agustín Ruiz; Guzmán, Adrian; Zamora-Gutiérrez, Diana; Mendoza, Germán David; Melgoza, Luz María; Montes, Sergio; Rosales-Torres, Ana María

    2015-08-01

    The aim of the present study was to evaluate the effects of L-arginine-HCl supplementation on ovulation rate, fertility, prolificacy, and serum VEGF concentrations in ewes with synchronized oestrus. Thirty Suffolk ewes with a mean body weight of 45 ± 3 kg and a mean body condition score (BCS) of 2.4 ± 0.28 were synchronized for estrus presentation with a progestin-containing sponge (20 mg Chronogest® CR) for 9 days plus PGF2-α (Lutalyse; Pfizer, USA) on day 7 after the insertion of the sponge. The ewes were divided into two groups; i.e., a control group (n = 15) that was fed on the native pasture (basal diet) and an L-arginine-HCl group (n = 15) that received 7.8 g of rumen-protected L-arginine-HCl from day 5 of the sponge insertion until day 25 after mating plus the basal diet. The L-arginine-HCl was administered daily via an esophageal probe between days 5 and 9 of the synchronization protocol and every third day subsequently. Blood samples were drawn from the jugular vein every 6 days throughout the entire experimental period. The results revealed that the L-arginine-HCl supplementation increased fertility during the synchronized estrus (P = 0.05). However, no effects were observed on the final BCS (P = 0.78), estrus presentation (P = 0.33), multiple ovulations (P = 0.24), prolificacy (P = 0.63), or serum VEGF concentration. In conclusion, L-arginine-HCl supplementation during the period used in this study increased fertility in sheep with synchronized estrus possibly due to improved embryo-fetal survival during early pregnancy.

  15. Immunogenicity, Safety and Reactogenicity of a Booster Dose of the 10-Valent Pneumococcal Nontypeable H. influenzae Protein D Conjugate Vaccine Coadministered With DTPa-IPV-Hib in Dutch Children: A Randomized Controlled Trial.

    Science.gov (United States)

    van den Bergh, Menno R; Spijkerman, Judith; François, Nancy; Swinnen, Kristien; Borys, Dorota; Schuerman, Lode; Veenhoven, Reinier H; Sanders, Elisabeth A M

    2016-07-01

    Immune responses and safety profiles may be affected when vaccines are coadministered. We evaluated the immunogenicity, safety and reactogenicity of a booster dose of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate (PHiD-CV; Synflorix GSK Vaccines) and DTPa-IPV-Hib (Pediacel Sanofi Pasteur MSD) when coadministered. We performed booster assessment in a randomized controlled trial in the Netherlands. Of 780 enrolled healthy infants, 774 toddlers participated in the booster phase and received (1:1:1) (1) PHiD-CV + DTPa-HBV-IPV/Hib (Infanrix hexa, GSK Vaccines), (2) PHiD-CV + DTPa-IPV-Hib, or (3) 7-valent pneumococcal conjugate vaccine (7vCRM, Prevenar/Prevnar, Pfizer, Inc.) + DTPa-IPV-Hib at 2, 3, 4 and 11-13 months old. Blood samples were taken postprimary, prebooster, 1 and 12 months postbooster. Antipneumococcal antibody responses were comparable between both PHiD-CV groups, except for serotype 18C (conjugated to tetanus toxoid). Anti-18C antibody geometric mean concentrations (GMCs) were higher when coadministered with DTPa-HBV-IPV/Hib. For each vaccine serotype, the percentages of children with antibody concentration ≥ 0.20 μg/mL were within the same ranges between PHiD-CV groups (93.8%-100%). The same was observed for the percentages of participants with opsonophagocytic activity titer ≥ 8 (90.9%-100%). When comparing both DTPa-IPV-Hib groups, postbooster antidiphtheria antibody GMCs were higher when coadministered with 7vCRM, while antitetanus and antipolyribosyl-ribitol phosphate antibody GMCs were higher with PHiD-CV coadministration. Regardless, antibody levels to these antigens were well above thresholds. Safety and reactogenicity profiles were comparable between groups. Coadministration of a booster dose of PHiD-CV and DTPa-IPV-Hib was immunogenic and well tolerated.

  16. Moving mountains.

    Science.gov (United States)

    2003-01-01

    What could be more fundamental to management, or more difficult, than motivating people? After all, a manager, by definition, is someone who gets work done through others. But how? A typical recipe for motivation calls for a mixture of persuasion, encouragement, and compulsion. Yet the best leaders, we suspect, need no recipe: They get people to produce great results by appealing to their deepest drives, needs, and desires. And so we discovered when we asked a dozen of the world's top leaders to describe how they each met a daunting challenge in motivating an individual, a team, or an organization. Their answers are as varied as human nature. Some of the leaders appeal to people's need for the rational and the orderly: Mattel's Robert Eckert emphasizes the reassuring power of delivering a consistent message, and HP's Carly Fiorina focuses on facing hard truths on setting step-by-step goals. Some, like celebrated oceanographer Robert Ballard, Pfizer CEO Hank McKinnell, and BP America president Ross Pillari, see the powerful motivating effects of asking people to rise to difficult challenges. Others focus more on the human spirit, appealing to the desire to do something, as BMW's Chris Bangle puts it, "rare, marvelous, and lasting." And quite a few inspire through example, as Dial chairman Herb Baum did when he donated $1,000 from his bonus to each of the company's 155 lowest-paid people. "If you draw the line on your own greed, and your employees see it," he says, "they will be incredibly loyal and perform much better for you." And he has the numbers to prove it. "Right now," he adds, "we're experiencing our lowest level of attrition in 11 years, and we're tracking toward another banner year because people are happy."

  17. Cross-packaging of genetically distinct mouse and primate retroviral RNAs

    Directory of Open Access Journals (Sweden)

    Jaballah Soumeya

    2009-07-01

    Full Text Available Abstract Background The mouse mammary tumor virus (MMTV is unique from other retroviruses in having multiple viral promoters, which can be regulated by hormones in a tissue specific manner. This unique property has lead to increased interest in studying MMTV replication with the hope of developing MMTV based vectors for human gene therapy. However, it has recently been reported that related as well as unrelated retroviruses can cross-package each other's genome raising safety concerns towards the use of candidate retroviral vectors for human gene therapy. Therefore, using a trans complementation assay, we looked at the ability of MMTV RNA to be cross-packaged and propagated by an unrelated primate Mason-Pfizer monkey virus (MPMV that has intracellular assembly process similar to that of MMTV. Results Our results revealed that MMTV and MPMV RNAs could be cross-packaged by the heterologous virus particles reciprocally suggesting that pseudotyping between two genetically distinct retroviruses can take place at the RNA level. However, the cross-packaged RNAs could not be propagated further indicating a block at post-packaging events in the retroviral life cycle. To further confirm that the specificity of cross-packaging was conferred by the packaging sequences (ψ, we cloned the packaging sequences of these viruses on expression plasmids that generated non-viral RNAs. Test of these non-viral RNAs confirmed that the reciprocal cross-packaging was primarily due to the recognition of ψ by the heterologous virus proteins. Conclusion The results presented in this study strongly argue that MPMV and MMTV are promiscuous in their ability to cross-package each other's genome suggesting potential RNA-protein interactions among divergent retroviral RNAs proposing that these interactions are more complicated than originally thought. Furthermore, these observations raise the possibility that MMTV and MPMV genomes could also co-package providing substrates for

  18. Improving diabetes medication adherence: successful, scalable interventions

    Directory of Open Access Journals (Sweden)

    Zullig LL

    2015-01-01

    Full Text Available Leah L Zullig,1,2 Walid F Gellad,3,4 Jivan Moaddeb,2,5 Matthew J Crowley,1,2 William Shrank,6 Bradi B Granger,7 Christopher B Granger,8 Troy Trygstad,9 Larry Z Liu,10 Hayden B Bosworth1,2,7,11 1Center for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center, Durham, NC, USA; 2Department of Medicine, Duke University, Durham, NC, USA; 3Center for Health Equity Research and Promotion, Pittsburgh Veterans Affairs Medical Center, Pittsburgh, PA, USA; 4Division of General Internal Medicine, University of Pittsburgh, Pittsburgh, PA, USA; 5Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA; 6CVS Caremark Corporation; 7School of Nursing, Duke University, Durham, NC, USA; 8Department of Medicine, Division of Cardiology, Duke University School of Medicine, Durham, NC, USA; 9North Carolina Community Care Networks, Raleigh, NC, USA; 10Pfizer, Inc., and Weill Medical College of Cornell University, New York, NY, USA; 11Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA Abstract: Effective medications are a cornerstone of prevention and disease treatment, yet only about half of patients take their medications as prescribed, resulting in a common and costly public health challenge for the US healthcare system. Since poor medication adherence is a complex problem with many contributing causes, there is no one universal solution. This paper describes interventions that were not only effective in improving medication adherence among patients with diabetes, but were also potentially scalable (ie, easy to implement to a large population. We identify key characteristics that make these interventions effective and scalable. This information is intended to inform healthcare systems seeking proven, low resource, cost-effective solutions to improve medication adherence. Keywords: medication adherence, diabetes mellitus, chronic disease, dissemination research

  19. Effect of Discontinuation or Initiation of Methotrexate or Glucocorticoids on Tofacitinib Efficacy in Patients with Rheumatoid Arthritis: A Post Hoc Analysis.

    Science.gov (United States)

    Fleischmann, Roy; Wollenhaupt, Jürgen; Cohen, Stanley; Wang, Lisy; Fan, Haiyun; Bandi, Vara; Andrews, John; Takiya, Liza; Bananis, Eustratios; Weinblatt, Michael E

    2018-06-01

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We evaluated the effect of concomitant methotrexate (MTX) or glucocorticoid (GC) use on tofacitinib clinical efficacy. Data were pooled from two open-label, long-term extension studies of tofacitinib 5 or 10 mg twice daily in patients with RA. Response according to Clinical Disease Activity Index (CDAI) was assessed separately in patients who discontinued (no MTX/GC use within 30 days prior to year-3 visit; assessment at month 3/year 3) or initiated (on/before year 3; assessment at initiation and year 3) MTX/GC. By year 3, among patients receiving background MTX at baseline, 186/1608 (11.6%) discontinued MTX, and 319/1434 (22.2%) patients receiving GC at baseline discontinued GC. Overall, 70.4/69.1% of patients who discontinued/continued MTX and 72.7/65.9% who discontinued/continued GC achieved CDAI remission or low disease activity (LDA) at year 3. Month 3 remission/LDA rates were maintained at year 3 in the majority of patients, irrespective of MTX/GC discontinuation/continuation. By year 3, 6.2% of patients receiving tofacitinib without MTX at baseline had initiated concomitant MTX, and 25.1% receiving tofacitinib without GC initiated GC; 69.0% and 45.4% initiating MTX or GC, respectively, had a CDAI-defined incomplete response prior to initiation. RA signs/symptoms improved following MTX initiation; only modest improvement was observed with GC initiation. Patients achieving remission/LDA with tofacitinib may discontinue MTX or GC and maintain treatment response. Patients with an incomplete response may benefit from adding concomitant MTX. Pfizer Inc. Study A3921024 [NCT00413699] and Study A3921041 [NCT00661661].

  20. PHARMACEUTICAL PARTNERSHIPS IN THE DEVELOPMENT OF NEW PHARMACEUTICALS

    Directory of Open Access Journals (Sweden)

    A. L. Bulgakov

    2018-01-01

    Full Text Available This article examines the causes for creating alliances between manufacturers and drug developers. The attention has also been paid to the classification of such partnerships depending on the level of integration. The classification is necessary for further study of relations in the alliances. It is important to understand how economically effective and justified such partnerships are. The aim of the study is to determine the reasons for creating partnerships between drug developers and manufacturers, and to work out a classification of partnerships in the field of pharmacology. Materials and methods. The study analyzes existing alliances, partnerships of Big Pharma companies such as Bayer AG, Merck & Co, Pfizer. Results and discussion. The variety of forms of partnerships allows all participants in this market to get from cooperation the benefits they need. Some seek to reduce risk, others look forward to gaining access to new research opportunities, the third seek to share knowledge for greater productivity. However, there is always the opposite side, they have to sacrifice something to get a market advantage. For example, increased integration leads to a reduction in the risk of drug creation, but also leads to a decrease in the company’s independence. Conclusion. The results of this study can be used later in the study of the financial effectiveness of pharmaceutical partnerships, as well as in exploring the causes of alliances’ collapses. Any partnership has its value and can be considered as an intangible asset of the company. However, at the moment, there is no universal way of assessing this type of active assets, therefore, classification is a key step in creating a model for determining the value of a partnership. 

  1. Temporal analysis of pain responders and common adverse events: when do these first appear following treatment with pregabalin

    Directory of Open Access Journals (Sweden)

    Parsons B

    2015-06-01

    Full Text Available Bruce Parsons, Birol Emir, Andrew Clair Pfizer, New York, NY, USA Background: Pregabalin is an α2δ ligand indicated in the USA for treatment of a number of chronic pain conditions, including diabetic peripheral neuropathy, postherpetic neuralgia, pain associated with spinal cord injury, and fibromyalgia. A greater understanding of when patients first respond to treatment with pregabalin and when adverse events emerge, or worsen, could aid design of new proof-of-concept studies and help guide treatment of patients. Methods: This was an analysis of five randomized, placebo-controlled, double-blind trials (between 8 and 16 weeks in duration of flexible-dose pregabalin (150–600 mg/day. Individual patient data were pooled into three groups by disease condition: diabetic peripheral neuro-pathy or postherpetic neuralgia (n=514, spinal cord injury (n=356, and fibromyalgia (n=498. Responders were classified as having a ≥30% and/or ≥50% reduction in mean pain score from baseline; once a patient responded, they were not scored subsequently (and were excluded from the responder analysis. The emergence of adverse events at each week was also recorded. Results: The majority of the 30% and 50% responders emerged within the first 3–4 weeks with pregabalin, but were more uniformly distributed across the 6 weeks of the analysis with placebo. The majority of common adverse events also emerged within the first 3–4 weeks of pregabalin treatment. Conclusion: These data suggest that the majority of pain responders and common adverse events emerge within 3–4 weeks of treatment with pregabalin. These data could advise new proof-of-concept studies and guide clinical management. Keywords: neuropathic pain, fibromyalgia, clinical trial design

  2. Cost minimization analysis of different growth hormone pen devices based on time-and-motion simulations

    Directory of Open Access Journals (Sweden)

    Kim Jaewhan

    2010-04-01

    Full Text Available Abstract Background Numerous pen devices are available to administer recombinant Human Growth Hormone (rhGH, and both patients and health plans have varying issues to consider when selecting a particular product and device for daily use. Therefore, the present study utilized multi-dimensional product analysis to assess potential time involvement, required weekly administration steps, and utilization costs relative to daily rhGH administration. Methods Study objectives were to conduct 1 Time-and-Motion (TM simulations in a randomized block design that allowed time and steps comparisons related to rhGH preparation, administration and storage, and 2 a Cost Minimization Analysis (CMA relative to opportunity and supply costs. Nurses naïve to rhGH administration and devices were recruited to evaluate four rhGH pen devices (2 in liquid form, 2 requiring reconstitution via TM simulations. Five videotaped and timed trials for each product were evaluated based on: 1 Learning (initial use instructions, 2 Preparation (arrange device for use, 3 Administration (actual simulation manikin injection, and 4 Storage (maintain product viability between doses, in addition to assessment of steps required for weekly use. The CMA applied micro-costing techniques related to opportunity costs for caregivers (categorized as wages, non-drug medical supplies, and drug product costs. Results Norditropin® NordiFlex and Norditropin® NordiPen (NNF and NNP, Novo Nordisk, Inc., Bagsværd, Denmark took less weekly Total Time (p ® Pen (GTP, Pfizer, Inc, New York, New York or HumatroPen® (HTP, Eli Lilly and Company, Indianapolis, Indiana. Time savings were directly related to differences in new package Preparation times (NNF (1.35 minutes, NNP (2.48 minutes GTP (4.11 minutes, HTP (8.64 minutes, p Conclusions Time-and-motion simulation data used to support a micro-cost analysis demonstrated that the pen device with the greater time demand has highest net costs.

  3. Diverse activities of viral cis-acting RNA regulatory elements revealed using multicolor, long-term, single-cell imaging.

    Science.gov (United States)

    Pocock, Ginger M; Zimdars, Laraine L; Yuan, Ming; Eliceiri, Kevin W; Ahlquist, Paul; Sherer, Nathan M

    2017-02-01

    Cis-acting RNA structural elements govern crucial aspects of viral gene expression. How these structures and other posttranscriptional signals affect RNA trafficking and translation in the context of single cells is poorly understood. Herein we describe a multicolor, long-term (>24 h) imaging strategy for measuring integrated aspects of viral RNA regulatory control in individual cells. We apply this strategy to demonstrate differential mRNA trafficking behaviors governed by RNA elements derived from three retroviruses (HIV-1, murine leukemia virus, and Mason-Pfizer monkey virus), two hepadnaviruses (hepatitis B virus and woodchuck hepatitis virus), and an intron-retaining transcript encoded by the cellular NXF1 gene. Striking behaviors include "burst" RNA nuclear export dynamics regulated by HIV-1's Rev response element and the viral Rev protein; transient aggregations of RNAs into discrete foci at or near the nuclear membrane triggered by multiple elements; and a novel, pulsiform RNA export activity regulated by the hepadnaviral posttranscriptional regulatory element. We incorporate single-cell tracking and a data-mining algorithm into our approach to obtain RNA element-specific, high-resolution gene expression signatures. Together these imaging assays constitute a tractable, systems-based platform for studying otherwise difficult to access spatiotemporal features of viral and cellular gene regulation. © 2017 Pocock et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  4. Hemostatic foam from radiation-modified carboxymethyl derivative of chitosan

    International Nuclear Information System (INIS)

    Barba, Bin Jeremiah D.; Aranilla, Charito T.; Vista, Jeanina Richelle M.; Relleve, Lorna S.; Abad, Lucille V.

    2015-01-01

    A hemostatic agent or hemostat is intended to accelerate the blood clotting process when applied to a bleeding surface, such as those in military and civilian wound trauma or in surgery. Natural polymers like chitosan (Ch) has been previously used as raw material in developing hemostats owing to their bioavailability and biocompatibility. Hydrogels were made from its carboxymethylated derivate (CMCh) and were crosslinked by gamma irradiation at a dose of 30 kGy. Further processing was done by salt leaching with sodium chloride and lyophilization to produce the foam hemostat. The final products were then radiation-sterilized at 25 kGy. The use of gamma radiation for both the crosslinking and sterilization process preserves the biocompatibility of the product unlike conventional methods that may require the use of harmful and non-biocompatible chemicals. The hemostatic efficacy of the designed foam hemostats was compared to the commercially available foam hemostat, GELFOAM Sterile Compressed Sponge by Pfizer. The results showed a significantly higher efficiency of the designed products using in vitro test to determine blood clotting index and platelet adhesion capacity. Characterization by gel fraction, swelling capacity and SEM imaging indicated a hydrophilic three-dimensional network which can be attributed for the thrombogenicity of the foams produced. The foam structure can act as a physical matrix for platelet adhesion forming the mechanical plug and at the same time, rapidly absorb water thereby locally increasing the concentration of platelets and physiological coagulation factors that will contribute to quick and efficient hemostasis. The designed products will provide the healthcare and military sector with a local alternative to the commercial products which are both expensive (USD 85 per piece) and not readily accessible in the Philippine market. Further animal efficacy and biocompatibility studies are recommended to supplement the positive in vitro

  5. Mortality associated with gastrointestinal bleeding events: Comparing short-term clinical outcomes of patients hospitalized for upper GI bleeding and acute myocardial infarction in a US managed care setting

    Directory of Open Access Journals (Sweden)

    C Mel Wilcox

    2009-03-01

    Full Text Available C Mel Wilcox1, Byron L Cryer2, Henry J Henk3, Victoria Zarotsky3, Gergana Zlateva41University of Alabama, Birmingham, AL, USA; 2University of Texas Southwestern Medical School, Dallas, TX; 3i3 Innovus, Eden Prairie, MN, USA; 4Pfizer, Inc., New York, NY, USA Objectives: To compare the short-term mortality rates of gastrointestinal (GI bleeding to those of acute myocardial infarction (AMI by estimating the 30-, 60-, and 90-day mortality among hospitalized patients.Methods: United States national health plan claims data (1999–2003 were used to identify patients hospitalized with a GI bleeding event. Patients were propensity-matched to AMI patients with no evidence of GI bleed from the same US health plan.Results: 12,437 upper GI-bleed patients and 22,847 AMI patients were identified. Propensity score matching yielded 6,923 matched pairs. Matched cohorts were found to have a similar Charlson Comorbidity Index score and to be similar on nearly all utilization and cost measures (excepting emergency room costs. A comparison of outcomes among the matched cohorts found that AMI patients had higher rates of 30-day mortality (4.35% vs 2.54%; p < 0.0001 and rehospitalization (2.56% vs 1.79%; p = 0.002, while GI bleed patients were more likely to have a repeat procedure (72.38% vs 44.95%; p < 0.001 following their initial hospitalization. The majority of the difference in overall 30-day mortality between GI bleed and AMI patients was accounted for by mortality during the initial hospitalization (1.91% vs 3.58%.Conclusions: GI bleeding events result in significant mortality similar to that of an AMI after adjusting for the initial hospitalization.Keywords: gastrointestinal, bleeding, mortality, acute myocardial infarction, claims analysis

  6. [Bacterial etiology of acute otitis media in Spain in the post-pneumococcal conjugate vaccine era].

    Science.gov (United States)

    Pumarola, Felix; Salamanca de la Cueva, Ignacio; Sistiaga-Hernando, Alessandra; García-Corbeira, Pilar; Moraga-Llop, Fernando A; Cardelús, Sara; McCoig, Cynthia; Gómez Martínez, Justo Ramón; Rosell Ferrer, Rosa; Iniesta Turpin, Jesús; Devadiga, Raghavendra

    2016-11-01

    Acute otitis media (AOM) is common in children aged <3 years. A pneumococcal conjugate vaccine (PCV) (PCV7; Prevenar, Pfizer/Wyeth, USA) has been available in Spain since 2001, which has a coverage rate of 50-60% in children aged <5 years. Children aged ≥3 to 36 months with AOM confirmed by an ear-nose-throat specialist were enrolled at seven centers in Spain (February 2009-May 2012) (GSK study identifier: 111425). Middle-ear-fluid samples were collected by tympanocentesis or spontaneous otorrhea and cultured for bacterial identification. Culture-negative samples were further analyzed using polymerase chain reaction (PCR). Of 125 confirmed AOM episodes in 124 children, 117 were analyzed (median age: 17 months (range: 3-35); eight AOM episodes were excluded from analyses. Overall, 69% (81/117) episodes were combined culture- and PCR-positive for ≥1 bacterial pathogen; 44% (52/117) and 39% (46/117) were positive for Haemophilus influenzae (Hi) and Streptococcus pneumoniae (Spn), respectively. 77 of 117 episodes were cultured for ≥1 bacteria, of which 63 were culture-positive; most commonly Spn (24/77; 31%) and Hi (32/77; 42%). PCR on culture-negative episodes identified 48% Hi- and 55% Spn-positive episodes. The most common Spn serotype was 19F (4/24; 17%) followed by 19A (3/24; 13%); all Hi-positive episodes were non-typeable (NTHi). 81/117 AOM episodes (69%) occurred in children who had received ≥1 pneumococcal vaccine dose. NTHi and Spn were the main etiological agents for AOM in Spain. Impact of pneumococcal vaccination on AOM requires further evaluation in Spain, after higher vaccination coverage rate is reached. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Efficient assessment of efficacy in post-traumatic peripheral neuropathic pain patients: pregabalin in a randomized, placebo-controlled, crossover study

    Directory of Open Access Journals (Sweden)

    Jenkins TM

    2012-07-01

    Full Text Available Tim M Jenkins, Trevor S Smart, Frances Hackman, Carol Cooke, Keith KC TanClinical Research, Pfizer Worldwide Research and Development, Sandwich, Kent, UKBackground: Detecting the efficacy of novel analgesic agents in neuropathic pain is challenging. There is a critical need for study designs with the desirable characteristics of assay sensitivity, low placebo response, reliable pain recordings, low cost, short duration of exposure to test drug and placebo, and relevant and recruitable population.Methods: We designed a proof-of-concept, double-blind, randomized, placebo-controlled, crossover study in patients with post-traumatic peripheral neuropathic pain (PTNP to evaluate whether such a study design had the potential to detect efficacious agents. Pregabalin, known to be efficacious in neuropathic pain, was used as the active analgesic. We also assessed physical activity throughout the study.Results: Twenty-five adults (20–70 years of age with PTNP for ≥3 months entered a screening week and were then randomized to one of the two following treatment sequences: (1 pregabalin followed by placebo or (2 placebo followed by pregabalin. These 2-week treatment periods were separated by a 2-week washout period. Patients on pregabalin treatment received escalating doses to a final dosage of 300 mg/day (days 5–15. In an attempt to minimize placebo response, patients received placebo treatment during the screening week and the 2-week washout period. Average daily pain scores (primary endpoint were significantly reduced for pregabalin versus placebo, with a mean treatment difference of -0.81 (95% confidence interval: -1.45 to -0.17; P = 0.015.Conclusion: The efficacy of pregabalin was similar to that identified in a large, parallel group trial in PTNP. Therefore, this efficient crossover study design has potential utility for future proof-of-concept studies in neuropathic pain.Keywords: pregabalin, post-traumatic peripheral neuropathic pain, randomized

  8. Deaths among adult patients with hypopituitarism: hypocortisolism during acute stress, and de novo malignant brain tumors contribute to an increased mortality.

    Science.gov (United States)

    Burman, P; Mattsson, A F; Johannsson, G; Höybye, C; Holmer, H; Dahlqvist, P; Berinder, K; Engström, B E; Ekman, B; Erfurth, E M; Svensson, J; Wahlberg, J; Karlsson, F A

    2013-04-01

    Patients with hypopituitarism have an increased standardized mortality rate. The basis for this has not been fully clarified. To investigate in detail the cause of death in a large cohort of patients with hypopituitarism subjected to long-term follow-up. All-cause and cause-specific mortality in 1286 Swedish patients with hypopituitarism prospectively monitored in KIMS (Pfizer International Metabolic Database) 1995-2009 were compared to general population data in the Swedish National Cause of Death Registry. In addition, events reported in KIMS, medical records, and postmortem reports were reviewed. Standardized mortality ratios (SMR) were calculated, with stratification for gender, attained age, and calendar year during follow-up. An excess mortality was found, 120 deaths vs 84.3 expected, SMR 1.42 (95% confidence interval: 1.18-1.70). Infections, brain cancer, and sudden death were associated with significantly increased SMRs (6.32, 9.40, and 4.10, respectively). Fifteen patients, all ACTH-deficient, died from infections. Eight of these patients were considered to be in a state of adrenal crisis in connection with death (medical reports and post-mortem examinations). Another 8 patients died from de novo malignant brain tumors, 6 of which had had a benign pituitary lesion at baseline. Six of these 8 subjects had received prior radiation therapy. Two important causes of excess mortality were identified: first, adrenal crisis in response to acute stress and intercurrent illness; second, increased risk of a late appearance of de novo malignant brain tumors in patients who previously received radiotherapy. Both of these causes may be in part preventable by changes in the management of pituitary disease.

  9. Preclinical Data on Efficacy of 10 Drug-Radiation Combinations: Evaluations, Concerns, and Recommendations

    Directory of Open Access Journals (Sweden)

    Helen B. Stone

    2016-02-01

    Full Text Available BACKGROUND: Clinical testing of new therapeutic interventions requires comprehensive, high-quality preclinical data. Concerns regarding quality of preclinical data have been raised in recent reports. This report examines the data on the interaction of 10 drugs with radiation and provides recommendations for improving the quality, reproducibility, and utility of future studies. The drugs were AZD6244, bortezomib, 17-DMAG, erlotinib, gefitinib, lapatinib, oxaliplatin/Lipoxal, sunitinib (Pfizer, Corporate headquarters, New York, NY, thalidomide, and vorinostat. METHODS: In vitro and in vivo data were tabulated from 125 published papers, including methods, radiation and drug doses, schedules of administration, assays, measures of interaction, presentation and interpretation of data, dosimetry, and conclusions. RESULTS: In many instances, the studies contained inadequate or unclear information that would hamper efforts to replicate or intercompare the studies, and that weakened the evidence for designing and conducting clinical trials. The published reports on these drugs showed mixed results on enhancement of radiation response, except for sunitinib, which was ineffective. CONCLUSIONS: There is a need for improved experimental design, execution, and reporting of preclinical testing of agents that are candidates for clinical use in combination with radiation. A checklist is provided for authors and reviewers to ensure that preclinical studies of drug-radiation combinations meet standards of design, execution, and interpretation, and report necessary information to ensure high quality and reproducibility of studies. Improved design, execution, common measures of enhancement, and consistent interpretation of preclinical studies of drug-radiation interactions will provide rational guidance for prioritizing drugs for clinical radiotherapy trials and for the design of such trials.

  10. Effect of P2X(7) receptor knockout on exocrine secretion of pancreas, salivary glands and lacrimal glands.

    Science.gov (United States)

    Novak, Ivana; Jans, Ida M; Wohlfahrt, Louise

    2010-09-15

    The purinergic P2X(7) receptors are expressed in different cell types where they have varied functions, including regulation of cell survival. The P2X(7) receptors are also expressed in exocrine glands, but their integrated role in secretion is unclear. The aim of our study was to determine whether the P2X(7) receptors affect fluid secretion in pancreas, salivary glands and tear glands. We monitored gland secretions in in vivo preparations of wild-type and P2X(7)(-/-) (Pfizer) mice stimulated with pilocarpine. In cell preparations from pancreas, parotid and lacrimal glands we measured ATP release and intracellular Ca(2+) activity using Fura-2. The data showed that pancreatic secretion and salivary secretions were reduced in P2X(7)(-/-) mice, and in contrast, tear secretion was increased in P2X(7)(-/-) mice. The secretory phenotype was also dependent on the sex of the animal, such that males were more dependent on the P2X(7) receptor expression. ATP release in all cell preparations could be elicited by carbachol and other agonists, and this was independent of the P2X(7) receptor expression. ATP and carbachol increased intracellular Ca(2+) activity, but responses depended on the gland type, presence of the P2X(7) receptor and the sex of the animal. Together, these results demonstrate that cholinergic stimulation leads to release of ATP that can via P2X(7) receptors up-regulate pancreatic and salivary secretion but down-regulate tear secretion. Our data also indicate that there is an interaction between purinergic and cholinergic receptor signalling and that function of the P2X(7) receptor is suppressed in females. We conclude that the P2X(7) receptors are important in short-term physiological regulation of exocrine gland secretion.

  11. Effect of P2X7 receptor knockout on exocrine secretion of pancreas, salivary glands and lacrimal glands

    Science.gov (United States)

    Novak, Ivana; Jans, Ida M; Wohlfahrt, Louise

    2010-01-01

    The purinergic P2X7 receptors are expressed in different cell types where they have varied functions, including regulation of cell survival. The P2X7 receptors are also expressed in exocrine glands, but their integrated role in secretion is unclear. The aim of our study was to determine whether the P2X7 receptors affect fluid secretion in pancreas, salivary glands and tear glands. We monitored gland secretions in in vivo preparations of wild-type and P2X7−/− (Pfizer) mice stimulated with pilocarpine. In cell preparations from pancreas, parotid and lacrimal glands we measured ATP release and intracellular Ca2+ activity using Fura-2. The data showed that pancreatic secretion and salivary secretions were reduced in P2X7−/− mice, and in contrast, tear secretion was increased in P2X7−/− mice. The secretory phenotype was also dependent on the sex of the animal, such that males were more dependent on the P2X7 receptor expression. ATP release in all cell preparations could be elicited by carbachol and other agonists, and this was independent of the P2X7 receptor expression. ATP and carbachol increased intracellular Ca2+ activity, but responses depended on the gland type, presence of the P2X7 receptor and the sex of the animal. Together, these results demonstrate that cholinergic stimulation leads to release of ATP that can via P2X7 receptors up-regulate pancreatic and salivary secretion but down-regulate tear secretion. Our data also indicate that there is an interaction between purinergic and cholinergic receptor signalling and that function of the P2X7 receptor is suppressed in females. We conclude that the P2X7 receptors are important in short-term physiological regulation of exocrine gland secretion. PMID:20643770

  12. Differences in reporting of analyses in internal company documents versus published trial reports: comparisons in industry-sponsored trials in off-label uses of gabapentin.

    Directory of Open Access Journals (Sweden)

    S Swaroop Vedula

    Full Text Available BACKGROUND: Details about the type of analysis (e.g., intent to treat [ITT] and definitions (i.e., criteria for including participants in the analysis are necessary for interpreting a clinical trial's findings. Our objective was to compare the description of types of analyses and criteria for including participants in the publication (i.e., what was reported with descriptions in the corresponding internal company documents (i.e., what was planned and what was done. Trials were for off-label uses of gabapentin sponsored by Pfizer and Parke-Davis, and documents were obtained through litigation. METHODS AND FINDINGS: For each trial, we compared internal company documents (protocols, statistical analysis plans, and research reports, all unpublished, with publications. One author extracted data and another verified, with a third person verifying discordant items and a sample of the rest. Extracted data included the number of participants randomized and analyzed for efficacy, and types of analyses for efficacy and safety and their definitions (i.e., criteria for including participants in each type of analysis. We identified 21 trials, 11 of which were published randomized controlled trials, and that provided the documents needed for planned comparisons. For three trials, there was disagreement on the number of randomized participants between the research report and publication. Seven types of efficacy analyses were described in the protocols, statistical analysis plans, and publications, including ITT and six others. The protocol or publication described ITT using six different definitions, resulting in frequent disagreements between the two documents (i.e., different numbers of participants were included in the analyses. CONCLUSIONS: Descriptions of analyses conducted did not agree between internal company documents and what was publicly reported. Internal company documents provide extensive documentation of methods planned and used, and trial

  13. Pericentriolar Targeting of the Mouse Mammary Tumor Virus GAG Protein.

    Directory of Open Access Journals (Sweden)

    Guangzhi Zhang

    Full Text Available The Gag protein of the mouse mammary tumor virus (MMTV is the chief determinant of subcellular targeting. Electron microscopy studies show that MMTV Gag forms capsids within the cytoplasm and assembles as immature particles with MMTV RNA and the Y box binding protein-1, required for centrosome maturation. Other betaretroviruses, such as Mason-Pfizer monkey retrovirus (M-PMV, assemble adjacent to the pericentriolar region because of a cytoplasmic targeting and retention signal in the Matrix protein. Previous studies suggest that the MMTV Matrix protein may also harbor a similar cytoplasmic targeting and retention signal. Herein, we show that a substantial fraction of MMTV Gag localizes to the pericentriolar region. This was observed in HEK293T, HeLa human cell lines and the mouse derived NMuMG mammary gland cells. Moreover, MMTV capsids were observed adjacent to centrioles when expressed from plasmids encoding either MMTV Gag alone, Gag-Pro-Pol or full-length virus. We found that the cytoplasmic targeting and retention signal in the MMTV Matrix protein was sufficient for pericentriolar targeting, whereas mutation of the glutamine to alanine at position 56 (D56/A resulted in plasma membrane localization, similar to previous observations from mutational studies of M-PMV Gag. Furthermore, transmission electron microscopy studies showed that MMTV capsids accumulate around centrioles suggesting that, similar to M-PMV, the pericentriolar region may be a site for MMTV assembly. Together, the data imply that MMTV Gag targets the pericentriolar region as a result of the MMTV cytoplasmic targeting and retention signal, possibly aided by the Y box protein-1 required for the assembly of centrosomal microtubules.

  14. Roflumilast: APTA 2217, B9302-107, BY 217, BYK 20869.

    Science.gov (United States)

    2004-01-01

    Roflumilast [APTA 2217, B9302-107, BY 217, BYK 20869] is a selective phosphodiesterase IV inhibitor. It is being developed by Altana Pharma (formerly Byk Gulden), a subsidiary of Altana Group, as an orally administered therapy for asthma, chronic obstructive pulmonary disease (COPD), allergic rhinitis and psoriasis. The drug is awaiting regulatory approval in Europe for the treatment of asthma and COPD. Byk Gulden has stated that roflumilast relieves asthma symptoms through both an anti-inflammatory effect and a muscle relaxant effect. Roflumilast has potential as first-line long-term therapy in mild-to-moderate COPD and as additive long-term therapy in moderate-to-severe COPD. Altana has stated that roflumilast is to be marketed under the brand name Daxas. Altana Group and Pharmacia Corporation (now Pfizer) signed an agreement on 22 April 2002 to collaborate on the development and commercialisation of roflumilast for the treatment of respiratory disorders, including asthma and COPD. The companies will jointly develop the drug for the US, Europe and other markets. Pharmacia will co-ordinate development in the US and Altana will co-ordinate development in Europe. After approval of the drug, Pharmacia and Altana will jointly launch and promote roflumilast in the US, Europe and elsewhere. Altana will receive an upfront payment and additional milestone payments. Altana additionally has the option to co-promote Pharmacia products in the US and elsewhere. On 16 April 2003, Pharmacia Corporation was acquired by, and merged into, Pfizer. In November 2002, Altana and Tanabe Seiyaku signed an agreement to collaborate on the development and commercialisation of roflumilast for the treatment of respiratory diseases, including asthma and COPD. Tanabe Seiyaku and Altana will develop roflumilast for asthma and COPD in Japan, and will jointly launch and co-promote roflumilast in Japan following regulatory approval. Roflumilast has been in multinational phase III clinical studies

  15. CME/CNE Article: A Framework of Care in Multiple Sclerosis, Part 1: Updated Disease Classification and Disease-Modifying Therapy Use in Specific Circumstances.

    Science.gov (United States)

    Newsome, Scott D; Aliotta, Philip J; Bainbridge, Jacquelyn; Bennett, Susan E; Cutter, Gary; Fenton, Kaylan; Lublin, Fred; Northrop, Dorothy; Rintell, David; Walker, Bryan D; Weigel, Megan; Zackowski, Kathleen; Jones, David E

    2016-01-01

    (author), has served on scientific advisory boards for Biogen, Genentech, Novartis, and Genzyme, and has performed contracted research (institution received funds) for Biogen, Genentech, and Novartis. Philip J. Aliotta, MD, MSHA, CHCQM, FACS (author), has served on speakers' bureaus for Astellas Pharma, Actavis, Augmenix, and Allergan and has performed contracted research for Allergan. Jacquelyn Bainbridge, PharmD (author), has disclosed no relevant financial relationships. Susan E. Bennett, PT, DPT, EdD, NCS, MSCS (author), has served on speakers' bureaus for Acorda Therapeutics, Biogen, and Medtronic; has received consulting fees from and performed contracted research for Acorda Therapeutics; and is chair of the Clinical Events Committee at Innovative Technologies. Gary Cutter, PhD (author), has participated on Data and Safety Monitoring Committees for AMO Pharma, Apotek, Gilead Pharmaceuticals, Horizon Pharmaceuticals, Modigenetech/Prolor, Merck, Merck/Pfizer, Opko Biologics, Neuren, Sanofi-Aventis, Reata Pharmaceuticals, Receptos/Celgene, Teva Pharmaceuticals, NHLBI (Protocol Review Committee), and NICHD (OPRU Oversight Committee); has received consulting fees from and/or served on speakers' bureaus and scientific advisory boards for Cerespir, Genzyme, Genentech, Innate Therapeutics, Janssen Pharmaceuticals, Klein-Buendel Incorporated, MedImmune, Medday, Nivalis, Novartis, Opexa Therapeutics, Roche, Savara, Somahlution, Teva Pharmaceuticals, Transparency Life Sciences, and TG Therapeutics; and is President of Pythagoras, Inc., a private consulting company located in Birmingham, AL. Kaylan Fenton, CRNP, APNP, MSCN (author), has disclosed no relevant financial relationships. Fred Lublin, MD (author), has received consulting fees/fees for non-CME/CE activities from Bayer HealthCare Pharmaceuticals, Biogen, EMD Serono, Novartis, Teva Neuroscience, Actelion, Sanofi/Genzyme, Acorda, Questcor/Mallinckrodt, Roche/Genentech, MedImmune, Osmotica, Xenoport, Receptos

  16. Comparative effectiveness and costs of generic and brand-name gabapentin and venlafaxine in patients with neuropathic pain or generalized anxiety disorder in Spain

    Directory of Open Access Journals (Sweden)

    Sicras-Mainar A

    2015-06-01

    Full Text Available Antoni Sicras-Mainar,1 Javier Rejas-Gutiérrez,2 Ruth Navarro-Artieda3 1Planning Directorate, Badalona Serveis Assistencials SA, Badalona, Barcelona, Spain; 2Department of Health Economics and Outcomes Research, Pfizer SLU, Alcobendas, Madrid, Spain; 3Medical Documentation, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain Objective: To explore adherence/persistence with generic gabapentin/venlafaxine versus brand-name gabapentin/venlafaxine (Neurontin®/Vandral® in peripheral neuropathic pain (pNP or generalized anxiety disorder (GAD, respectively, and whether it is translated into different costs and patient outcomes in routine medical practice. Methods: A retrospective, new-user cohort study was designed. Electronic medical records (EMR of patients included in the health plan of Badalona Serveis Assistencials SA, Barcelona, Spain were exhaustively extracted for analysis. Participants were beneficiaries aged 18+ years, followed between 2008 and 2012, with a pNP/GAD International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM code, who initiated treatment with generic or brand-name gabapentin or venlafaxine. Assessments included 1-year treatment persistence and adherence (medication possession ratio, health care costs, and reduction in severity of pain and anxiety symptoms. Results: A total of 2,210 EMR were analyzed; 1,369 on gabapentin (brand 400; generic 969 and 841 on venlafaxine (brand 370 and generic 471. Brand-name gabapentin and venlafaxine were both significantly associated with longer persistence than generic: 7.3 versus 6.3 months, P<0.001; and 8.8 versus 8.1 months, P<0.05, respectively. Brand-name was associated with higher adherence: 86.5% versus 81.3%, P<0.001; and 82.1% versus 79.0%, P<0.05, respectively. Adjusted average costs were higher with generic compared with brand: €1,277 versus €1,057 (difference of €220 per patient; P<0.001 for gabapentin; and €1,110 versus €928

  17. Apixaban versus warfarin in patients with atrial fibrillation.

    Science.gov (United States)

    Granger, Christopher B; Alexander, John H; McMurray, John J V; Lopes, Renato D; Hylek, Elaine M; Hanna, Michael; Al-Khalidi, Hussein R; Ansell, Jack; Atar, Dan; Avezum, Alvaro; Bahit, M Cecilia; Diaz, Rafael; Easton, J Donald; Ezekowitz, Justin A; Flaker, Greg; Garcia, David; Geraldes, Margarida; Gersh, Bernard J; Golitsyn, Sergey; Goto, Shinya; Hermosillo, Antonio G; Hohnloser, Stefan H; Horowitz, John; Mohan, Puneet; Jansky, Petr; Lewis, Basil S; Lopez-Sendon, Jose Luis; Pais, Prem; Parkhomenko, Alexander; Verheugt, Freek W A; Zhu, Jun; Wallentin, Lars

    2011-09-15

    and Pfizer; ARISTOTLE ClinicalTrials.gov number, NCT00412984.).

  18. Efficacy and safety of imidacloprid 10% plus moxidectin 2.5% spot-on in the treatment of sarcoptic mange and otoacariosis in dogs: results af a European field study.

    Science.gov (United States)

    Krieger, K; Heine, J; Dumont, P; Hellmann, K

    2005-10-01

    Efficacy and safety of treatment with imidacloprid 10%+moxidectin 2.5% spot-on (Advocate, Advantage multi; Bayer AG, Leverkusen, Germany) were tested in dogs naturally infested with Sarcoptes scabiei or Otodectes cynotis in a multi-centre, controlled, randomized, blinded field study conducted in France, Germany, Albania and the UK. The study was performed according to a non-inferiority design to demonstrate that the efficacy of imidacloprid/moxidectin spot-on was not inferior to that of a control product containing selamectin (Stronghold spot-on; Pfizer). All Sarcoptes-infested dogs were topically treated twice (days 0 and 28) with the dosage recommended by the respective manufacturer (27 dogs with imidacloprid/moxidectin, 26 with selamectin). All Otodectes-infested dogs were treated on day 0 (35 dogs with imidacloprid/moxidectin, 34 with selamectin), and only those still positive on day 28 received a second treatment. Parasitological cure rate in Sarcoptes-infested dogs was 100% for both treatments, while parasitological cures rates in the Otodectes-infested dogs at day 28 and day 56 were 68.6 and 85.7% with imidacloprid/moxidectin, and 64.7 and 88.2% with Stronghold. Non-inferiority of Advocate was confirmed statistically. Clinical assessment of skin lesion scores at day 56 showed that with either product >96% of the dogs treated against sarcoptic mange were improved or cured, the difference between the groups being non-significant. On the basis of a final clinical assessment of lesion scores, 80% of the dogs treated with imidacloprid/moxidectin against otoacariosis and 85.3% of those treated with selamectin were rated cured or improved. Only three mild, possibly drug-related adverse reactions were observed among alI treated animals (two in the imidacloprid/moxidectin group, one in the selamectin group). It is concluded that imidacloprid/moxidectin spot-on is an effective and safe treatment for sarcoptic mange and otoacariosis in the dog.

  19. Observational longitudinal study of symptom burden and time for recovery from community-acquired pneumonia reported by older adults surveyed nationwide using the CAP Burden of Illness Questionnaire

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    Wyrwich KW

    2015-07-01

    Full Text Available Kathleen W Wyrwich,1 Holly Yu,2 Reiko Sato,2 John H Powers31Evidera, Inc., Bethesda, MD, USA; 2Pfizer Inc., Collegeville, PA, USA; 3George Washington University School of Medicine and Health Sciences, Washington, DC, USABackground: Millions of older adults who develop community-acquired pneumonia (CAP each year survive, but there is a large knowledge gap on the burden of CAP and the recovery process in survivors from the patient perspective.Methods: The newly developed CAP Burden of Illness Questionnaire was administered through a Web survey to a nationwide sample of US adults aged ≥50 years who were recently diagnosed with CAP. Survey respondents with unresolved symptoms or other CAP-related health problems completed a second survey 30 days later; a third survey was completed another 30 days later by respondents with unresolved symptoms or problems. Nationally representative results describing the average time to recovery of symptoms and other CAP-related problems were achieved using post-stratification weights.Results: Five hundred participants completed the initial survey. The time to resolution for the CAP symptoms of weakness, shortness of breath, and tiredness exceeded 3 weeks on average. There was an average of 13 days of absenteeism, and 3 weeks (mean =21 days before achieving full work/activity productivity after CAP. For participants with health conditions that worsened from pneumonia, chronic emphysema and chronic obstructive pulmonary disease took the longest to return to baseline (mean =60 and 52.4 days, respectively.Conclusion: The results from this study demonstrate that older adults surviving a CAP episode experience a significant multi-symptom illness with long recovery periods to achieve pre-CAP health and productivity. These findings highlight the need for further research on effective clinician–patient communication, the need for patient-centered outcomes in clinical trials for CAP therapeutics, adequate home care during

  20. Reduction of porcine circovirus type 2 (PCV2 viremia by a reformulated inactivated chimeric PCV1-2 vaccine-induced humoral and cellular immunity after experimental PCV2 challenge

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    Seo Hwi

    2012-10-01

    Full Text Available Abstract Background The objective of the present study was to elucidate the humoral and cellular immune response mechanisms by which a reformulated inactivated chimeric PCV1-2 vaccine reduces the PCV2 viremia. Forty PCV2 seronegative 3-week-old pigs were randomly divided into the following four groups: vaccinated challenged (T01, vaccinated non-challenged (T02, non-vaccinated challenged (T03, and non-vaccinated non-challenged (T04 animals. The pigs in groups T01 and T02 were immunized with a reformulated inactivated chimeric PCV1-2 vaccine (Fostera™ PCV; Pfizer Animal Health administered as a 2.0 ml dose at 21 days of age. At 35 days of age (0 days post-challenge, the pigs in groups T01 and T03 were inoculated intranasally with 2 ml each of PCV2b. Results A reduction of PCV2 viremia coincided with the appearance of both PCV2-specific neutralizing antibodies (NA and interferon-γ-secreting cells (IFN-γ-SCs in the vaccinated animals. However, the presence of anti-PCV2 IgG antibodies did not correlate with the reduction of PCV2 viremia. Lymphocyte subset analysis indicated that the numbers of CD3+ and CD4+ cells increased in vaccinated animals but the numbers of CD4+ cells decreased transiently in non-vaccinated animals. The observation of a delayed type hypersensitivity response in only the vaccinated animals also supports a CD4+ cell-associated protective cellular immune response induced by the reformulated inactivated chimeric PCV1-2 vaccine. Conclusions The induction of PCV2-specific NA and IFN-γ-SCs, and CD4+ cells by the reformulated inactivated chimeric PCV1-2 vaccine is the important protective immune response leading to reduction of the PCV2 viremia and control of the PCV2 infection. To our knowledge this is the first demonstration of protective humoral and cellular immunity induced by the reformulated inactivated chimeric PCV1-2 vaccine and its effect on reduction of PCV2 viremia by vaccination.

  1. The burden of family caregiving in the United States: work productivity, health care resource utilization, and mental health among employed adults

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    Hopps M

    2017-12-01

    Full Text Available Markay Hopps, Laura Iadeluca, Margaret McDonald, Geoffrey T MakinsonPfizer Inc., New York, NY, USA Background: Family caregiving is an increasingly important component of care for patients and the elderly. Objective: The aim of this study is to characterize the burden of family caregiving among employed adults. Methods: Employed adults (≥18 years from the 2013 US National Health and Wellness Survey (NHWS were classified as family caregivers if they reported currently caring for at least one adult relative. Chi-square tests and one-way analyses of variance assessed whether employed caregivers, weighted to the US population, differed from employed non-caregivers on behavioral characteristics, workplace productivity, and health care resource utilization. Results: Eight million workers were family caregivers in the United States, more often female than male (51% vs. 49%, P < 0.05, and 53% were between 40 and 64 years of age. Eighteen percent of caregivers were Hispanic compared with 15% of non-caregivers (P < 0.05. Similar behavioral characteristics between caregivers and non-caregivers included daily alcohol consumption (6% vs. 5% and lack of vigorous exercise (25% vs. 29%, but caregivers had a higher prevalence of smoking (26% vs. 19%, P < 0.05. Caregivers reported a higher mean percentage of work time missed (8% vs. 4%, P < 0.05 and greater productivity impairment (24% vs. 14%, P < 0.05. Some form of depression was reported by 53% of caregivers compared with 32% of non-caregivers (P < 0.05, and more caregivers had self-reported insomnia than non-caregivers (46% vs. 37%, P < 0.05. The number of self-reported diagnosed comorbidities was higher among caregivers compared with that of non-caregivers (5.0 vs. 3.1, P < 0.05, as was the mean number of outpatient visits in the previous 6 months (4.1 vs. 2.7, P < 0.05. Conclusion: Family caregiving is associated with a multidimensional burden that impacts caregivers and has implications for

  2. Medicine as a corporate enterprise, patient welfare centered profession, or patient welfare centered professional enterprise?

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    Singh, Ajai; Singh, Shakuntala

    2005-11-01

    There is an alarming trend in the field of medicine, whose portents are ominous but do not seem to shake the complacency and merry making doing the rounds.The wants of the medical man have multiplied beyond imagination. The cost of organizing conferences is no longer possible on delegate fees. The bottom-line is: Crores for a Conference Millions for a Mid-Term. However, the problem is that sponsors keep a discreet but careful tab on docs. All in all, costs of medicines escalate, and quality medical care becomes a luxury. The whole brunt of this movement is borne by the patient.Companies like GlaxoSmithKline, Bayer, Pfizer, Bristol-Myers Squibb, AstraZeneca, Schering-Plough, Abbott Labs, TAP Pharmaceuticals, Wyeth and Merck have paid millions of dollars each as compensation in the last few years. The financial condition of many pharmaceutical majors is not buoyant either. Price deflation, increased Rand D spending, and litigation costs are the main reasons. In the future, the messy lawsuits situation would no longer be restricted to industry. It would involve academia and practising doctors as well. Indian pharma industry captains, who were busy raking in the profits at present, would also come under the scanner. If nothing else, it means industry and docs will have to sit down and do some soul searching.Both short and long-term measures will have to be put into place. Short-term measures involve reduction in i) pharma spending over junkets and trinkets; ii) hype over 'me too' drugs; iii) manipulation of drug trials; iv) getting pliant researchers into drug trials; iv) manipulation of Journal Editors to publish positive findings about their drug trials and launches; v) and for Indian Pharma, to conduct their own unbiased clinical trial of the latest drug projected as a blockbuster in the West, before pumping in their millions.The long-term measures are related to the way biomedical advance is to be charted. We have to decide whether medicine is to become a corporate

  3. Gold implant therapy of locomotory disorders in dogs - Case studies

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    Emilia Abrudean

    2016-06-01

    Full Text Available The case study was conducted between October and January 2015, on 7 dogs of different breeds and ages, which at clinical examination showed varying degrees of lameness. The dogs behavior and state of consciousness, their attitude in standing, decubitus and at walk and the presence of involuntary movements was assessed through inspection. Palpation was used to feel muscular tonus, local temperature and sensibility. Postural reactions were highlighted by carrying out forced positions of each limb, thus highlighting the proprioceptive sensitivity. By testing the spinal reflexes the reactions of the forelimbs and hind limbs were evaluated, seeking the state of normality, or the absence, diminution or exacerbation of these reflexes. Also, diagnostic imaging was performed consisting of simple radiographs, were performed for the cases that entered the clinic. In the case of digital X-rays, X-rays are passing through the subject being examined are filtered, then touch a plate of sensors able to convert signals generated into digital information with an image appear on the computer screen. Interpretation of results was done by assessing the degree of dysplasia, and the Norberg-Olson angle and stage. This study used digital radiography as imaging technique; the device was Rx-M EVO Fujifilm. On the basis of diagnostic imaging and computerized image, diagnosis was established for each case. The treatment protocol with gold implant was the same for all seven cases; the adopted procedure was the "Wiener" procedure, described by Kasper and Zohmann. The procedure began with establishing a set of points associated with the treatment of hip dysplasia, spondylosis, arthritis, and osteochondritis. For the therapeutic protocol to be performed correctly took the dogs were sedated. This was done with medetomidine hydrochloride (Dorbene vet, Pfizer, concentration 1 mg⁄ml, administered in a 0,1mg⁄kg body weight dose. The results were visible after a month from the

  4. Abnormal subchondral bone microstructure following steroid administration is involved in the early pathogenesis of steroid-induced osteonecrosis.

    Science.gov (United States)

    Wang, L; Zhang, L; Pan, H; Peng, S; Zhao, X; Lu, W W

    2016-01-01

    Loss of bone microstructure integrity is thought to be related to osteonecrosis. But the relationship between the time when bone microstructure integrity loss appears and the onset of osteonecrosis has not yet been determined. Our study demonstrated abnormal changes of subchondral bone microstructure involved in the early pathogenesis of osteonecrosis. Using a rabbit model, we investigated the changes of subchondral bone microstructure following steroid administration to identify the onset of abnormal bone microstructure development in steroid-induced osteonecrosis. Fifty-five adult female Japanese White rabbits (mean body weight 3.5 kg; mean age 24 months) were used and randomly divided among three time points (3, 7, and 14 days) consisting of 15 rabbits each, received a single intramuscular injection of methylprednisolone acetate (MP; Pfizer Manufacturing Belgium NV) at a dose of 4 mg/kg, and a control group consisting of 10 rabbits was fed and housed under identical conditions but were not given steroid injections. A micro-CT scanner was applied to detect changes in the trabecular region of subchondral bone of excised femoral head samples. Parameters including bone volume fraction (BV/TV), bone surface (BS), trabecular bone pattern factor (Tb.Pf), trabecular thickness/number/separation (Tb.Th, Tb.N, and Tb.Sp), and structure model index (SMI) were evaluated using the software CTAn (SkyScan). After micro-CT scans, bilateral femoral heads were cut in the coronal plane at a thickness of 4 μm. The sections were then stained with haematoxylin-eosin and used for the diagnosis of osteonecrosis and the rate of development of osteonecrosis. The BV/TV, BS, Tb.Th and Tb.N demonstrated a time-dependent decline from 3, 7, and 14 days compared with the control group, while the Tb.Pf, Tb.Sp and SMI demonstrated an increase at 3, 7, and 14 days compared with the control group. For the histopathology portion, osteonecrosis was not seen 3 days after steroid treatment, but was

  5. Persistent efficacy of a long acting injectable formulation of moxidectin against natural infestations of the sheep nasal bot (Oestrus ovis) in Spain.

    Science.gov (United States)

    Rugg, Douglas; Ferrer, Luis Miguel; Sarasola, Patxi; Figueras, Luis; Lacasta, Delia; Liu, Bo; Bartram, David

    2012-09-10

    Cydectin(®) 2% LA Solution for Injection for Sheep (Pfizer Animal Health) is a long-acting (LA) formulation of moxidectin for the treatment and prevention of mixed infections of gastro-intestinal nematodes, respiratory nematodes and certain arthropod parasites in sheep. To evaluate the duration of persistent efficacy against nasal bots (Oestrus ovis), a natural exposure study was conducted in Spain during the summer of 2011. One hundred and twenty nasal bot-free, Rasa Aragonesa sheep were randomly allocated to eight groups of 15 animals each. On Day 0, four groups were treated at the recommended dose rate of 1 mg moxidectin/kg bodyweight. Four groups remained untreated as negative controls. All animals were held in nasal bot-proof housing except for exposure to natural challenge when one group of treated sheep and one of group of control animals were transferred to a local pasture at either 0-20, 20-40, 40-60, or 60-80 days after treatment. Following challenge, sheep were scored for clinical signs of bot infestation, necropsied and the heads sectioned for larval recovery. Nasal bot larvae were retrieved from 7 to 11 control sheep following each exposure period indicating that adult bots were active throughout the study. In the first challenge up to 20 days after treatment, when sheep were slaughtered immediately after exposure, the majority of larvae were first instar (L1) and only 3 of the 15 control sheep were infested with second instars (L2). There was 100% efficacy against L2 and 38.1% reduction in the number of live L1 in the treated sheep but mean counts were not significantly different between treatment and control groups (P ≥ 0.05). For the subsequent exposure periods 20-80 days after treatment (necropsies 7-9 days after challenge), 6-10 sheep were infested with L1 and 9-11 control sheep were infested with L2 and third instars (L3). There was negligible efficacy against L1, but treatment with moxidectin resulted in 100% control of L2 and L3. These

  6. The burden of selected cancers in the US: health behaviors and health care resource utilization

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    Iadeluca L

    2017-11-01

    Full Text Available Laura Iadeluca,1 Jack Mardekian,1 Pratibha Chander,2 Markay Hopps,1 Geoffrey T Makinson1 1Pfizer Inc., 2Atrium Staffing, New York, NY, USA Objective: To characterize the disease burden among survivors of those cancers having the highest incidence in the US.Methods: Adult (≥18 years survivors of the 11 most frequently diagnosed cancers were identified from publically available data sources, including the Surveillance Epidemiology and End Results 9 1973–2012, National Health Interview Survey 2013, and the Medical Expenditure Panel Survey 2011. Chi-square tests and one-way analyses of variance were utilized to assess differences between cancer survivors and non-cancer controls in behavioral characteristics, symptoms and functions, preventative screenings, and health care costs.Results: Hematologic malignancies, melanoma, and breast, prostate, lung, colon/rectal, bladder, kidney/renal, uterine, thyroid, and pancreatic cancers had the highest incidence rates. Breast cancer had the highest incidence among women (156.4 per 100,000 and prostate cancer among men (167.2 per 100,000. The presence of pain (P=0.0003, fatigue (P=0.0005, and sadness (P=0.0012 was consistently higher in cancer survivors 40–64 years old vs. non-cancer controls. Cancer survivors ≥65 years old had higher rates of any functional limitations (P=0.0039 and reported a lack of exercise (P<0.0001 compared with the non-cancer controls. However, obesity rates were similar between cancer survivors and non-cancer controls. Among cancer survivors, an estimated 13.5 million spent $169.4 billion a year on treatment, with the highest direct expenditures for breast cancer ($39 billion, prostate cancer ($37 billion, and hematologic malignancies ($25 billion. Prescription medications and office-based visits contributed equally as the cost drivers of direct medical spending for breast cancer, while inpatient hospitalization was the driver for prostate (52.8% and lung (38.6% cancers

  7. Cost-effectiveness of routine measuring of serum drug concentrations and anti-drug antibodies in treatment of rheumatoid arthritis patients with TNF-α blockers

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    Laine J

    2016-04-01

    Full Text Available Juha Laine,1 T Sakari Jokiranta,2,3 Kari K Eklund,4,5 Merja Väkeväinen,1 Kari Puolakka6 1Pfizer Oy, Helsinki, 2United Medix Laboratories Ltd, Espoo, 3Research Programs Unit, Immunobiology, 4Department of Rheumatology, University of Helsinki, 5Helsinki University Central Hospital, Helsinki, 6Department of Medicine, South Karelia, Finland Abstract: Monitoring of anti-drug antibodies (ADAbs or serum concentrations of biologicals in treatment of rheumatoid arthritis could provide an explanation for a loss of efficacy and help in the choice of subsequent medication. Current clinical practices do not generally include such monitoring of tumor necrosis factor (TNF-α blockers on a routine basis. The main aims of this study were to estimate the probabilities of optimal and nonoptimal treatment decisions if infliximab or adalimumab drug trough level (DL and ADAbs are tested or not in rheumatoid arthritis, and to model cost-effectiveness of performing such monitoring on a routine basis. Data on DLs and ADAbs concentrations were obtained in Finland from clinically requested monitoring analyses of 486 and 1,137 samples from patients on adalimumab and infliximab, respectively. DL was within the target range in 42% of samples from adalimumab- and 50.4% of infliximab-treated patients. ADAbs were detected in approximately 20% and 13.5% of samples from adalimumab- and infliximab-treated patients, respectively. ADAbs were found in 52.3% and 41.3% of those with low adalimumab or infliximab DLs, respectively. The monitoring data were incorporated into probabilities for making the optimal treatment decision. Economic impact of clinical decision-making was modeled in a short-term (3–6 months scenario with 100 hypothetical patients. In the model, the combined measurement of DLs and ADAbs was cost-saving compared to the nontesting scenario when the monitoring results affected the treatment decision in at least 2–5 of 100 patients, a proportion which is easily

  8. Evaluation of Brazilian biotechnology patent activity from 1975 to 2010.

    Science.gov (United States)

    Dias, F; Delfim, F; Drummond, I; Carmo, A O; Barroca, T M; Horta, C C; Kalapothakis, E

    2012-08-01

    The analysis of patent activity is one methodology used for technological monitoring. In this paper, the activity of biotechnology-related patents in Brazil were analyzed through 30 International Patent Classification (IPC) codes published by the Organization for Economic Cooperation and Development (OECD). We developed a program to analyse the dynamics of the major patent applicants, countries and IPC codes extracted from the Brazilian Patent Office (INPI) database. We also identified Brazilian patent applicants who tried to expand protection abroad via the Patent Cooperation Treaty (PCT). We had access to all patents published online at the INPI from 1975 to July 2010, including 9,791 biotechnology patent applications in Brazil, and 163 PCTs published online at World Intellectual Property Organization (WIPO) from 1997 to December 2010. To our knowledge, there are no other online reports of biotechnology patents previous to the years analyzed here. Most of the biotechnology patents filed in the INPI (10.9%) concerned measuring or testing processes involving nucleic acids. The second and third places belonged to patents involving agro-technologies (recombinant DNA technology for plant cells and new flowering plants, i.e. angiosperms, or processes for obtaining them, and reproduction of flowering plants by tissue culture techniques). The majority of patents (87.2%) were filed by nonresidents, with USA being responsible for 51.7% of all biotechnology patents deposited in Brazil. Analyzing the resident applicants per region, we found a hub in the southeast region of Brazil. Among the resident applicants for biotechnology patents filed in the INPI, 43.5% were from São Paulo, 18.3% were from Rio de Janeiro, and 9.7% were from Minas Gerais. Pfizer, Novartis, and Sanofi were the largest applicants in Brazil, with 339, 288, and 245 biotechnology patents filed, respectively. For residents, the largest applicant was the governmental institution FIOCRUZ (Oswaldo Cruz

  9. Tranexamic acid for treatment of women with post-partum haemorrhage in Nigeria and Pakistan: a cost-effectiveness analysis of data from the WOMAN trial.

    Science.gov (United States)

    Li, Bernadette; Miners, Alec; Shakur, Haleema; Roberts, Ian

    2018-02-01

    -partum haemorrhage with tranexamic acid is highly cost-effective in Nigeria and Pakistan, and is likely to be cost-effective in countries in sub-Saharan Africa and southern Asia with a similar baseline risk of death due to bleeding. London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

  10. Prescription pain reliever misuse and levels of pain impairment: 3-year course in a nationally representative outpatient sample of US adults

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    Novak SP

    2016-06-01

    Full Text Available Scott P Novak,1 Cristie Glasheen,1 Carl L Roland,2 1Behavioral Health Epidemiology, RTI International, 2Clinical Sciences and Outcomes Evidence, Pfizer Inc., Durham, NC, USA Background: The primary aim of this work was to present the prevalence data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC, a representative 3-year longitudinal survey (ages 18+ years that captured information on patterns of self-reported pain interference and prescription pain reliever misuse. A second aim was to assess the degree to which the risk of various types of opioid misuse (onset, desistance, and incidence of dependence was related to the longitudinal course of self-reported pain interference over the 3-year period. Methods: We used a two-wave, nationally representative sample of adults (aged 18+ years in which the baseline data were collected during 2001–2002 and a single follow-up was obtained ~3 years later (2004–2005 with 34,332 respondents with complete data on study variables for both waves. Results: Our findings indicated that ~10% reported high pain interference in the past month at each wave. There was tremendous stability in levels of pain, with ~5% reporting consistent levels of high impairment over the 3-year study, a proxy for chronic pain. Levels of pain were more strongly associated with prescription pain reliever misuse concurrently rather than prospectively, and the association was largely linear, with the likelihood of misuse increasing with levels of pain. Finally, health service factors were also prominent predictors of onset, but not the outcomes, of desistance or transitions to problem use. Conclusion: This study is the first to use a nationally representative sample with measures of pain and drug use history collected over an extended period. These results may help provide clinicians with an understanding that the risk of misuse is greatest when pain is active and may help guide the selection of

  11. Health-resource use and costs associated with fibromyalgia in France, Germany, and the United States

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    Chandran A

    2013-04-01

    Full Text Available Tyler Knight,1 Caroline Schaefer,1 Arthi Chandran,2 Gergana Zlateva,2 Andreas Winkelmann,3 Serge Perrot4 1Health Economics and Outcomes Research, Covance Market Access Services, Gaithersburg, MD, USA; 2Primary Care Health Economics and Outcomes Research, Pfizer Global Health Economics, New York, NY, USA; 3Department of Physical Medicine and Rehabilitation, University Hospital Munich, Munich, Germany; 4Service de Médecine Interne et Thérapeutique, Université Paris Descartes, Paris, France Background: Fibromyalgia (FM is a chronic disorder characterized by widespread, persistent pain. Prospective and retrospective studies have demonstrated substantial health-care costs associated with FM in a number of countries. This study evaluated and compared health-resource use (HRU and associated costs related to FM in routine clinical practice across the US, France, and Germany. Methods: Two separate, cross-sectional, observational studies of subjects with FM were conducted: one in the US and one in France and Germany. HRU related to prescription medication, physician office visits, diagnostic tests, and hospitalizations was abstracted from chart review; patient out-of-pocket costs and lost productivity were collected via subject self-report. Costs were assigned to HRU based on standard algorithms. Direct and indirect costs were evaluated and compared by simple linear regression. Results: A total of 442 subjects (203 US, 70 France, 169 Germany with FM were analyzed. The mean (standard deviation age in the US, France, and Germany was 47.9 (10.9, 51.2 (9.5, and 49.2 (9.8, respectively (P = 0.085. Most subjects were female (95% US, 83% France, 80% Germany (P < 0.001. Adjusted annual direct costs per subject for FM were significantly higher in the US ($7087 than in France ($481, P < 0.001 or Germany ($2417, P < 0.001. Adjusted mean annual indirect costs per subject for FM were lower in the US ($6431 than in France ($8718 or Germany ($10,001, but represented

  12. Design, rationale, and baseline demographics of SEARCH I: a prospective cluster-randomized study

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    Albers F

    2012-07-01

    Full Text Available Frank Albers,1 Asif Shaikh,2 Ahmar Iqbal,31Medical Affairs Respiratory, 2Clinical Development and Medical Affairs, Field Based Medicine-Respiratory, Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT, USA; 3Respiratory Medical Affairs, Pfizer Inc, New York, NY, USAAbstract: Questionnaires are available to identify patients at risk for several chronic diseases, including COPD, but are infrequently utilized in primary care. COPD is often underdiagnosed, while at the same time the US Preventive Services Task Force recommends against spirometric screening for COPD in asymptomatic adults. Use of a symptom-based questionnaire and subsequent handheld spirometric device depending on the answers to the questionnaire is a promising approach to identify patients at risk for COPD. Screening, Evaluating and Assessing Rate CHanges of diagnosing respiratory conditions in primary care 1 (SEARCH I was a prospective cluster-randomized study in 168 US primary care practices evaluating the effect of the COPD-Population Screener (COPD-PS™ questionnaire. The effect of this questionnaire alone or sequentially with the handheld copd-6TM device was evaluated on new diagnoses of COPD and on respiratory diagnostic practice patterns (including referrals for pulmonary function testing, referrals to pulmonologists, new diagnoses of COPD, and new respiratory medication prescriptions. Participating practices entered a total of 9704 consecutive consenting subjects aged ≥ 40 years attending primary care clinics. Study arm results were compared for new COPD diagnosis rates between usual care and (1 COPD-PS plus copd-6 and (2 COPD-PS alone. A cluster-randomization design allowed comparison of the intervention effects at the practice level instead of individuals being the subjects of the intervention. Regional principal investigators controlled the flow of study information to sub-investigators at participating practices to reduce observation bias (Hawthorne effect. The

  13. Management of osteoporosis and menopausal symptoms: focus on bazedoxifene/conjugated estrogen combination

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    Mirkin S

    2013-08-01

    Full Text Available Sebastian Mirkin,1 James H Pickar21Pfizer Inc, Collegeville, PA, 2Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, NY, USAAbstract: Loss of estrogen production in women during menopause results in a state of estrogen deficiency which has been associated with multiple problems, including vasomotor symptoms, symptoms of vulvovaginal atrophy, bone loss, and difficulties with sleep, mood, memory, and sexual activity. The only treatment option currently available to address multiple postmenopausal symptoms in women with an intact uterus is estrogen/progestin-containing hormone therapy (HT. Concerns surrounding side effects and published data regarding the association of HT with the increased risk for breast cancer have induced a decrease in the number of women seeking, initiating, and continuing this type of therapy. A combination containing bazedoxifene and conjugated estrogens (BZA/CE maintains the established benefits of estrogen therapy for treatment of postmenopausal vasomotor symptoms, vulvovaginal atrophy, and osteoporosis, while certain estrogenic effects, such as stimulation of the uterus and breast, are antagonized without the side effects associated with HT. BZA/CE has been evaluated in a series of multicenter, randomized, double-blind, placebo-controlled, and active-controlled Phase III trials known as the Selective estrogens, Menopause, And Response to Therapy (SMART trials. BZA/CE demonstrated clinically meaningful improvements in vasomotor symptoms, vulvovaginal atrophy, and a protective effect on the skeleton. These clinical benefits were associated with an acceptable safety profile and an improved tolerability compared with HT. BZA/CE showed a favorable safety profile on the breast, endometrium, and ovaries. The incidence of venous thromboembolism was low and the risk does not appear to be any greater than for CE alone or BZA alone or greater than HT. The incidence of coronary heart disease and

  14. Tigecycline Susceptibility Trends Among Pathogens Isolated from Complicated Skin and Soft-Tissue Infections in North and Latin America: 2012–2016

    Science.gov (United States)

    Hoban, Daryl; Renteria, Martha; Leister-Tebbe, Heidi; Sahm, Dan

    2017-01-01

    surveillance monitoring is warranted. Disclosures M. Renteria, IHMA, Inc.: Employee, Salary. H. Leister-Tebbe, Pfizer: Employee, Salary

  15. A multicenter, primary-care-based, open-label study to assess the success of converting opioid-experienced patients with chronic moderate-to-severe pain to morphine sulfate and naltrexone hydrochloride extended-release capsules using a standardized conversion guide

    Directory of Open Access Journals (Sweden)

    Setnik B

    2015-07-01

    Full Text Available Beatrice Setnik,1 Carl L Roland,1 Kenneth W Sommerville,1,2 Glenn C Pixton,1 Robert Berke,3,4 Anne Calkins,5 Veeraindar Goli1,2 1Pfizer Inc, 2Duke University Medical Center, Durham, NC, USA; 3Family Health Medical Services PLLC, Mayville, 4Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, 5New York Spine & Wellness Center, Syracuse, NY, USA Objective: To evaluate the conversion of opioid-experienced patients with chronic moderate-to-severe pain to extended-release morphine sulfate with sequestered naltrexone hydrochloride (MSN using a standardized conversion guide. Methods: This open-label, single-arm study was conducted in 157 primary care centers in the United States. A total of 684 opioid-experienced adults with chronic moderate-to-severe pain were converted to oral administration of MSN from transdermal fentanyl and oral formulations of hydrocodone, hydromorphone, methadone, oxycodone, oxymorphone, and other morphine products using a standardized conversion guide. The primary endpoint was the percentage of patients achieving a stable MSN dose within a 6-week titration phase. Secondary endpoints included duration of time to stable dose, number of titration steps, safety and efficacy measures, and investigator assessment of conversion guide utility. Results: Of the 684 patients, 51.3% were converted to a stable dose of MSN (95% confidence interval: 47.5%, 55.1%. The mean (standard deviation number of days to stable dose was 20 (8.94, and number of titration steps to stable dose was 2.4 (1.37. The majority of adverse events were mild/moderate and consistent with opioid therapy. Mean pain scores at stable dose decreased from baseline. Investigators were generally satisfied with the conversion guide and, in 94% of cases, reported they would use it again. Conclusion: Conversion to MSN treatment using the standardized MSN conversion guide was an attainable goal in approximately half of the population of

  16. Study of the Effects of Total Modulation Transfer Function Changes on Observer Performance Using Clinical Mammograms.

    Science.gov (United States)

    Bencomo, Jose Antonio Fagundez

    The main goal of this study was to relate physical changes in image quality measured by Modulation Transfer Function (MTF) to diagnostic accuracy. One Hundred and Fifty Kodak Min-R screen/film combination conventional craniocaudal mammograms obtained with the Pfizer Microfocus Mammographic system were selected from the files of the Department of Radiology, at M.D. Anderson Hospital and Tumor Institute. The mammograms included 88 cases with a variety of benign diagnosis and 62 cases with a variety of malignant biopsy diagnosis. The average age of the patient population was 55 years old. 70 cases presented calcifications with 30 cases having calcifications smaller than 0.5mm. 46 cases presented irregular bordered masses larger than 1 cm. 30 cases presented smooth bordered masses with 20 larger than 1 cm. Four separated copies of the original images were made each having a different change in the MTF using a defocusing technique whereby copies of the original were obtained by light exposure through different thicknesses (spacing) of transparent film base. The mammograms were randomized, and evaluated by three experienced mammographers for the degree of visibility of various anatomical breast structures and pathological lesions (masses and calicifications), subjective image quality, and mammographic interpretation. 3,000 separate evaluations were anayzed by several statistical techniques including Receiver Operating Characteristic curve analysis, McNemar test for differences between proportions and the Landis et al. method of agreement weighted kappa for ordinal categorical data. Results from the statistical analysis show: (1) There were no statistical significant differences in the diagnostic accuracy of the observers when diagnosing from mammograms with the same MTF. (2) There were no statistically significant differences in diagnostic accuracy for each observer when diagnosing from mammograms with the different MTF's used in the study. (3) There statistical

  17. Adequacy of pharmacological information provided in pharmaceutical drug advertisements in African medical journals.

    Directory of Open Access Journals (Sweden)

    Oshikoya KA

    2009-06-01

    Full Text Available Pharmaceutical advertisement of drugs is a means of advocating drug use and their selling but not a substitute for drug formulary to guide physicians in safe prescribing. Objectives: To evaluate drug advertisements in Nigerian and other African medical journals for their adequacy of pharmacological information. Methods: Twenty four issues from each of West African Journal of Medicine (WAJM, East African Medical Journal (EAMJ, South African Medical Journal (SAMJ, Nigerian Medical Practitioner (NMP, Nigerian Quarterly Journal of Hospital Medicine (NQJHM and Nigerian Postgraduate Medical Journal (NPMJ were reviewed. While EAMJ, SAMJ and NMP are published monthly, the WAJM, NQJHM and NPMJ are published quarterly. The monthly journals were reviewed between January 2005 and December 2006, and the quarterly journals between January 2001 and December 2006. The drug information with regards to brand/non-proprietary name, pharmacological data, clinical information, pharmaceutical information and legal aspects was evaluated as per World Health Organisation (WHO criteria. Counts in all categories were collated for each advertiser.Results: Forty one pharmaceutical companies made 192 advertisements. 112 (58.3% of these advertisements were made in the African medical journals. Pfizer (20.3% and Swipha (12.5% topped the list of the advertising companies. Four (2.1% adverts mentioned generic names only, 157 (81.8% mentioned clinical indications. Adults and children dosage (39.6%, use in special situations such as pregnancy and renal or liver problems (36.5%, adverse effects (30.2%, average duration of treatment (26.0%, and potential for interaction with other drugs (18.7% were less discussed. Pharmaceutical information such as available dosage forms and product and package information {summary of the generic and proprietary names, the formulation strength, active ingredient, route of administration, batch number, manufactured and expiry dates, and the

  18. Improvement in pain severity category in clinical trials of pregabalin

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    Parsons B

    2016-10-01

    Full Text Available Bruce Parsons,1 Charles E Argoff,2 Andrew Clair,1 Birol Emir1 1Pfizer, New York, NY, USA; 2Albany Medical Center, Albany, NY, USA Background: Pregabalin is approved by the US Food and Drug Administration for the treatment of fibromyalgia (FM, diabetic peripheral neuropathy (DPN, postherpetic neuralgia (PHN, and neuropathic pain due to spinal cord injury (SCI. Approval was based on clinical trial data demonstrating statistically significant differences in pain scores versus placebo. However, statistically significant pain relief may not always equate to clinically meaningful pain relief. To further characterize the clinical benefit of pregabalin, this analysis examined shifts in pain severity categories in patients with FM, DPN/PHN (pooled in this analysis, and SCI treated with pregabalin.Methods: Data were pooled from 23 placebo-controlled trials in patients with FM (1,623 treated with pregabalin, 937 placebo, DPN/PHN (2,867 pregabalin, 1,532 placebo, or SCI (181 pregabalin, 175 placebo. Pain scores were assessed on an 11-point numeric rating scale and categorized as mild (0 to <4, moderate (4 to <7, or severe (7 to 10. Only patients with mean score ≥4 at baseline were randomized to treatment. The percentage of patients shifting pain category from baseline to endpoint for pregabalin and placebo was analyzed using a modified ridit transformation with the Cochran–Mantel–Haenszel procedure.Results: A higher proportion of patients shifted to a less severe pain category at endpoint with pregabalin compared with placebo. With flexible-dose pregabalin, the percentage of patients improving from: severe to mild (pregabalin versus placebo was 15.8 versus 13.4 in FM patients, 36.0 versus 16.6 in DPN/PHN patients, 14.3 versus 7.7 in SCI patients; severe to moderate was 28.7 versus 28.2 in FM patients, 32.5 versus 28.2 in DPN/PHN patients, 35.7 versus 28.2 in SCI patients; and moderate to mild was 38.3 versus 26.4 in FM patients, 59.5 versus 41.4 in

  19. Efficacy of imidacloprid + moxidectin and selamectin topical solutions against the KS1 Ctenocephalides felis flea strain infesting cats

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    Dryden Michael W

    2011-09-01

    Full Text Available Abstract Background Two studies were conducted to evaluate and compare the efficacy of imidacloprid + moxidectin and selamectin topical solutions against the KS1 flea strain infesting cats. In both studies the treatment groups were comprised of non-treated controls, 6% w/v selamectin (Revolution®; Pfizer Animal Health topical solution and 10% w/v imidacloprid + 1% w/v moxidectin (Advantage Multi® for Cats, Bayer Animal Health topical solution. All cats were infested with 100 fleas on Days -2, 7, 14, 21, and 28. The difference in the studies was that in study #1 efficacy evaluations were conducted at 24 and 48 hours post-treatment or post-infestation, and in study #2 evaluations were conducted at 12 and 24 hours. Results In study #1 imidacloprid + moxidectin and the selamectin formulation provided 99.8% and 99.0% efficacy at 24 hours post-treatment. On day 28, the 24 hour efficacy of the selamectin formulation dropped to 87.1%, whereas the imidacloprid + moxidectin formulation provided 98.9% efficacy. At the 48 hour assessments following the 28 day infestations, efficacy of the imidacloprid + moxidectin and selamectin formulations was 96.8% and 98.3% respectively. In study # 2 the efficacy of the imidacloprid + moxidectin and selamectin formulations 12 hours after treatment was 100% and 69.4%, respectively. On day 28, efficacy of the imidacloprid + moxidectin and selamectin formulations 12 hours after infestation was 90.2% and 57.3%, respectively. In study #2 both formulations provided high levels of efficacy at the 24 hour post-infestation assessments, with selamectin and imidacloprid + moxidectin providing 95.3% and 97.5% efficacy, following infestations on day 28. Conclusions At the 24 and 48 hour residual efficacy assessments, the imidacloprid + moxidectin and selamectin formulations were similarly highly efficacious. However, the imidacloprid + moxidectin formulation provided a significantly higher rate of flea kill against the KS1 flea

  20. Pain relief and functional improvement in patients with neuropathic pain associated with spinal cord injury: an exploratory analysis of pregabalin clinical trials

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    Sadosky A

    2016-06-01

    Full Text Available Alesia Sadosky,1 Bruce Parsons,1 Birol Emir,1 Edward C Nieshoff2 1Pfizer Inc., New York, NY, 2Rehabilitation Institute of Michigan, Detroit, MI, USA Background: Characterizing relationships between pain relief and function can inform patient management decisions. This analysis explored graphically the relationship between pain relief and functional improvement in patients with neuropathic pain associated with spinal cord injury in two clinical trials of pregabalin. Methods: This was a post hoc analysis of two randomized, double-blind, clinical trials in patients who were treated with pregabalin (n=181 or placebo (n=172 for neuropathic pain associated with spinal cord injury. The bivariate relationship between percent pain relief and absolute change in the functional outcomes with placebo and pregabalin was evaluated graphically using scatter plots, and loess curves illustrated the extent of the relationship between pain and function. Linear trend analysis evaluated the statistical significance of these relationships using Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT-based thresholds of pain reduction (<15%, 15% <30%, 30% to <50%, and ≥50%. Outcome measures included modified Brief Pain Inventory pain interference with function in one of the studies and the Medical Outcomes Study Sleep Scale (an 11-point Numeric Rating Scale and the Hospital Anxiety and Depression Scale (HADS for the pooled studies. Results: Data ellipses showed a shift with pregabalin relative to placebo toward greater improvement with increasing pain relief for all outcome measures except HADS. Loess curves suggested a relationship between increased pain relief and improved function except for HADS, with the clearest relationship observed for sleep. Linear trend analysis showed significant relationships between pain and Medical Outcomes Study Sleep Scale (P<0.0001 and between pain and function on the modified Brief Pain Inventory

  1. Secular Trends on Birth Parameters, Growth, and Pubertal Timing in Girls with Turner Syndrome

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    Joachim Woelfle

    2018-02-01

    Full Text Available BackgroundWhether children with chromosomal disorders of growth and puberty are affected by secular trends (STs as observed in the general population remains unanswered, but this question has relevance for expectations of spontaneous development and treatment responses.ObjectivesThe aim of the study was to evaluate STs in birth parameters, growth, and pubertal development in girls with Turner syndrome (TS.Study designRetrospective analysis of KIGS data (Pfizer International Growth Database. We included all TS patients who entered KIGS between 1987 and 2012 and were born from 1975 to 2004, who were prepubertal and growth treatment naïve at first entry (total number: 7,219. Pretreatment height and ages at the start of treatment were compared across 5-year birth year groups, with subgroup analyses stratified by induced or spontaneous puberty start.ResultsWe observed significant STs across the birth year groups for birth weight [+0.18 SD score (SDS, p < 0.001], pretreatment height at mean age 8 years (+0.73 SDS, p < 0.001, height at the start of growth hormone (GH therapy (+0.38 SDS, p < 0.001 and start of puberty (+0.42 SDS, p < 0.001. Spontaneous puberty onset increased from 15 to 30% (p < 0.001. Mean age at the start of GH treatment decreased from 10.8 to 7.4 years (−3.4 years; p < 0.001, and substantial declines were seen in ages at onset of spontaneous and induced puberty (−2.0 years; p < 0.001 and menarche (−2.1 years; p < 0.001.ConclusionEnvironmental changes leading to increased height and earlier and also more common, spontaneous puberty are applicable in TS as in normal girls. In addition, greater awareness for TS may underlie trends to earlier start of GH therapy and induction of puberty at a more physiological age.

  2. Exubera. Inhale therapeutic systems.

    Science.gov (United States)

    Bindra, Sanjit; Cefalu, William T

    2002-05-01

    Inhale, in colaboration with Pfizer and Aventis Pharma (formerly Hoechst Marion Roussel; HMR), is developing an insulin formulation utilizing its pulmonary delivery technology for macromolecules for the potential treatment of type I and II diabetes. By July 2001, the phase III program had been completed and the companies had begun to assemble data for MAA and NDA filings; however, it was already clear at this time that additional data might be required for filing. By December 2001, it had been decided that the NDA should include an increased level of controlled, long-term pulmonary safety data in diabetic patients and a major study was planned to be completed in 2002, with the NDA filed thereafter (during 2002). US-05997848 was issued to Inhale Therapeutic Systems in December 1999, and corresponds to WO-09524183, filed in February 1995. Equivalent applications have appeared to date in Australia, Brazil, Canada, China, Czech Republic, Europe, Finland, Hungary, Japan, Norway, New Zealand, Poland and South Africa. This family of applications is specific to pulmonary delivery of insulin. In February 1999, Lehman Brothers gave this inhaled insulin a 60% probability of reaching market, with a possible launch date of 2001. The analysts estimated peak sales at $3 billion in 2011. In May 2000, Aventis predicted that estimated peak sales would be in excess of $1 billion. In February 2000, Merrill Lynch expected product launch in 2002 and predicted that it would be a multibillion-dollar product. Analysts Merril Lynch predicted, in September and November 2000, that the product would be launched by 2002, with sales in that year of e75 million, rising to euro 500 million in 2004. In April 2001, Merrill Lynch predicted that filing for this drug would occur in 2001. Following the report of the potential delay in regulatory filing, issued in July 2001, Deutsche Banc Alex Brown predicted a filing would take place in the fourth quarter of 2002 and launch would take place in the first

  3. The dual kinase complex FAK-Src as a promising therapeutic target in cancer

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    Victoria Bolós

    2010-06-01

    Full Text Available Victoria Bolós1,*, Joan Manuel Gasent2,*, Sara López-Tarruella3, Enrique Grande1,#1Pfizer Oncology, Madrid, Spain; 2Hospital Gral. Universitario Marina Alta, Oncology Department, Denia Alicante, 3,#Hospital Clínico San Carlos, Oncology Department, ∗These authors contributed equally to this work, #Center affiliated to the Red Temática de Investigación Cooperativa (RD06/0020/0021. Instituto de Salud Carlos III (ISCIII, Spanish Ministry of Science and InnovationAbstract: Focal adhesion kinase (FAK and steroid receptor coactivator (Src are intracellular (nonreceptor tyrosine kinases that physically and functionally interact to promote a variety of cellular responses. Plenty of reports have already suggested an additional central role for this complex in cancer through its ability to promote proliferation and anoikis resistance in tumor cells. An important role for the FAK/Src complex in tumor angiogenesis has also been established. Furthermore, FAK and Src have been associated with solid tumor metastasis through their ability to promote the epithelial mesenchymal transition. In fact, a strong correlation between increased FAK/Src expression/phosphorylation and the invasive phenotype in human tumors has been found. Additionally, an association for FAK/Src with resistances to the current anticancer therapies has already been established. Currently, novel anticancer agents that target FAK or Src are under development in a broad variety of solid tumors. In this article we will review the normal cellular functions of the FAK/Src complex as an effector of integrin and/or tyrosine kinase receptor signaling. We will also collect data about their role in cancer and we will summarize the most recent data from the FAK and Src inhibitors under clinical and preclinical development. Furthermore, the association of both these proteins with chemotherapy and hormonal therapy resistances, as a rationale for new combined therapeutic approaches with these novel

  4. Carbon Management Brochure - Assessing and managing business responses to climate change

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-08-16

    The Carbon Management Programme, developed by the Carbon Trust and trialled with 50 leading companies, provides a systematic approach to managing the risks and realising the opportunities that climate change presents. In 2003-2004, the Carbon Trust successfully piloted the Carbon Management Programme with 50 leading UK companies including sixteen of the FTSE 100. The following sectors were represented: manufacturing, retail, finance, property and construction and food and drink. Alcan, Tesco, Pfizer, Royal Bank of Scotland, the companies that took part. For Scottish and Newcastle operational efficiency and reductions in cost base are vital to maintain competitive advantage. Moreover, as a branded goods company, Scottish and Newcastle has taken a leading position on its commitment to CSR and climate change mitigation. Carbon Management is a key part of this and has become a leading issue for investors, consumers and regulators. Scottish Courage undertook the Carbon Management Programme to explore further energy-efficiency potential, to seek CSR opportunities and to pilot ideas for potential international roll-out. The programme identified a wide range of opportunities and led to a plan to deliver annual energy cost savings of 15% as well as 13,000 tonnes of carbon emission reductions. The programme helped HBOS to understand the commercial implications of carbon issues on company activities, products, and services. It clarified the risk of climate change associated with property, lending and insurance portfolios; identified new product and service opportunities and facilitated internal engagement and raised the profile of Carbon Management issues within the company. The programme also highlighted opportunities for reputation and brand enhancement. For the Boots Group Carbon Management activities were aligned with corporate objectives for CSR, energy and transport. Site surveys were used to identify a list of specific carbon abatement projects. From this a 5-10 year

  5. Ability of Bottle Cap Color to Facilitate Accurate Patient-Physician Communication Regarding Medication Identity in Patients with Glaucoma.

    Science.gov (United States)

    Dave, Pujan; Villarreal, Guadalupe; Friedman, David S; Kahook, Malik Y; Ramulu, Pradeep Y

    2015-12-01

    To determine the accuracy of patient-physician communication regarding topical ophthalmic medication use based on bottle cap color, particularly among individuals who may have acquired color vision deficiency from glaucoma. Cross-sectional, clinical study. Patients aged ≥18 years with primary open-angle, primary angle-closure, pseudoexfoliation, or pigment dispersion glaucoma, bilateral visual acuity of ≥20/400, and no concurrent conditions that may affect color vision. A total of 100 patients provided color descriptions of 11 distinct medication bottle caps. Color descriptors were then presented to 3 physicians. Physicians matched each color descriptor to the medication they thought the descriptor was describing. Frequency of patient-physician agreement, occurring when all 3 physicians accurately matched the color descriptor to the correct medication. Multivariate regression models evaluated whether patient-physician agreement decreased with degree of better-eye visual field (VF) damage, color descriptor heterogeneity, or color vision deficiency, as determined by the Hardy-Rand-Rittler (HRR) score and Lanthony D15 color confusion index (D15 CCI). Subjects had a mean age of 69 (±11) years, with VF mean deviation of -4.7 (±6.0) and -10.9 (±8.4) decibels (dB) in the better- and worse-seeing eyes, respectively. Patients produced 102 unique color descriptors to describe the colors of the 11 bottle caps. Among individual patients, the mean number of medications demonstrating agreement was 6.1/11 (55.5%). Agreement was less than 15% for 4 medications (prednisolone acetate [generic], betaxolol HCl [Betoptic; Alcon Laboratories Inc., Fort Worth, TX], brinzolamide/brimonidine [Simbrinza; Alcon Laboratories Inc.], and latanoprost [Xalatan; Pfizer, Inc., New York, NY]). Lower HRR scores and higher D15 CCI (both indicating worse color vision) were associated with greater VF damage (P communication using bottle cap color alone may be common and could lead to confusion

  6. Reduction in cardiovascular risk using a proactive multifactorial intervention is consistent among patients residing in Pacific Asian and non-Pacific Asian regions: a CRUCIAL trial subanalysis

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    Cho EJ

    2014-03-01

    Full Text Available Eun Joo Cho,1 Jae Hyung Kim,1 Santosh Sutradhar,2 Carla Yunis,2 Mogens Westergaard2On behalf of the CRUCIAL trial investigators1Department of Cardiology, St Paul's Hospital, The Catholic University of Korea, Seoul, Korea; 2Pfizer Inc., New York, NY, USABackground: Few trials have compared different approaches to cardiovascular disease prevention among Pacific Asian (PA populations. The Cluster Randomized Usual Care versus Caduet Investigation Assessing Long-term-risk (CRUCIAL trial demonstrated that a proactive multifactorial intervention (PMI approach (based on single-pill amlodipine/atorvastatin resulted in a greater reduction in calculated Framingham 10-year coronary heart disease (CHD risk compared with usual care (UC among hypertensive patients with additional risk factors. One-third of CRUCIAL patients resided in the PA region. The aim of this subanalysis was to compare two approaches to cardiovascular risk factor management (PMI versus UC among patients residing in PA and non-PA regions.Methods: This subanalysis of the CRUCIAL trial compared treatment-related changes in calculated CHD risk among patients residing in PA and non-PA regions. Sensitivity analyses were conducted among men and women and those with and without diabetes.Results: Overall, 448 patients (31.6% resided in the PA region and 969 patients (68.4% resided in non-PA regions. The PMI approach was more effective in reducing calculated CHD risk versus UC in both PA (−37.1% versus −3.5%; P<0.001 and non-PA regions (−31.1% versus −4.2%; P<0.001; region interaction P=0.131. PA patients had slightly greater reductions in total cholesterol compared with non-PA patients. PA patients without diabetes had slightly greater reductions in CHD risk compared with non-PA patients. Treatment effects were similar in men and women and those with diabetes.Conclusion: The PMI approach was more effective in reducing calculated Framingham 10-year CHD risk compared with UC among men and

  7. Health care and social care costs of pneumonia in Denmark: a register-based study of all citizens and patients with COPD in three municipalities

    Directory of Open Access Journals (Sweden)

    Brogaard SL

    2015-10-01

    Full Text Available Susanne Lausten Brogaard,1 Maj Britt Dahl Nielsen,1 Lars Ulrik Nielsen,2 Trine Mosegaard Albretsen,3 Morten Bundgaard,4 Niels Anker,1 Maja Appel,1 Kim Gustavsen,1 Rose-Marie Lindkvist,5 Anne Skjoldan,2 Grete Breinhild,3 Peter Bo Poulsen5 1COWI AS, Management - Health, Kongens Lyngby, 2Seniors and Health Department, Gladsaxe Municipality, Welfare Technology, Søborg, 3Elderly and Health Care Department, Lolland Municipality, Maribo, 4Department of Public Health, Holbaek Municipality, Holbaek, 5Pfizer Denmark ApS, Health & Value, Ballerup, Denmark Background: Pneumonia is a frequent lung infection and a serious illness, which is often diagnosed among patients hospitalized with acute exacerbations of COPD. The aim of this study was to estimate the attributable costs due to pneumonia among patients hospitalized with pneumonia compared to a matched general population control group without pneumonia hospitalization.Methods: This study includes citizens older than 18 years from three municipalities (n=142,344. Based on national registers and municipal data, the health and social care costs of pneumonia in the second half of 2013 are estimated and compared with propensity score-matched population controls.Results: The average health care costs of 383 patients hospitalized with pneumonia in the second half of 2013 were US$34,561 per patient. Among pneumonia patients with COPD, the costs were US$35,022. The attributable costs of patients with pneumonia compared to the population control group for the 6-month period were US$24,155 per case. Overall, the attributable costs for the 383 pneumonia cases amounted to US$9.25 million. Subgroup analyses showed that costs increased with age. The attributable costs due to pneumonia were highest among the 18–59-year-old and the 70–79-year-old patients. This difference is likely to reflect an increased risk of mortality among the pneumonia patients. Men have higher costs than women in the pneumonia group

  8. Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy.

    Science.gov (United States)

    Ravaud, Alain; Motzer, Robert J; Pandha, Hardev S; George, Daniel J; Pantuck, Allan J; Patel, Anup; Chang, Yen-Hwa; Escudier, Bernard; Donskov, Frede; Magheli, Ahmed; Carteni, Giacomo; Laguerre, Brigitte; Tomczak, Piotr; Breza, Jan; Gerletti, Paola; Lechuga, Mariajose; Lin, Xun; Martini, Jean-Francois; Ramaswamy, Krishnan; Casey, Michelle; Staehler, Michael; Patard, Jean-Jacques

    2016-12-08

    Sunitinib, a vascular endothelial growth factor pathway inhibitor, is an effective treatment for metastatic renal-cell carcinoma. We sought to determine the efficacy and safety of sunitinib in patients with locoregional renal-cell carcinoma at high risk for tumor recurrence after nephrectomy. In this randomized, double-blind, phase 3 trial, we assigned 615 patients with locoregional, high-risk clear-cell renal-cell carcinoma to receive either sunitinib (50 mg per day) or placebo on a 4-weeks-on, 2-weeks-off schedule for 1 year or until disease recurrence, unacceptable toxicity, or consent withdrawal. The primary end point was disease-free survival, according to blinded independent central review. Secondary end points included investigator-assessed disease-free survival, overall survival, and safety. The median duration of disease-free survival was 6.8 years (95% confidence interval [CI], 5.8 to not reached) in the sunitinib group and 5.6 years (95% CI, 3.8 to 6.6) in the placebo group (hazard ratio, 0.76; 95% CI, 0.59 to 0.98; P=0.03). Overall survival data were not mature at the time of data cutoff. Dose reductions because of adverse events were more frequent in the sunitinib group than in the placebo group (34.3% vs. 2%), as were dose interruptions (46.4% vs. 13.2%) and discontinuations (28.1% vs. 5.6%). Grade 3 or 4 adverse events were more frequent in the sunitinib group (48.4% for grade 3 events and 12.1% for grade 4 events) than in the placebo group (15.8% and 3.6%, respectively). There was a similar incidence of serious adverse events in the two groups (21.9% for sunitinib vs. 17.1% for placebo); no deaths were attributed to toxic effects. Among patients with locoregional clear-cell renal-cell carcinoma at high risk for tumor recurrence after nephrectomy, the median duration of disease-free survival was significantly longer in the sunitinib group than in the placebo group, at a cost of a higher rate of toxic events. (Funded by Pfizer; S-TRAC Clinical

  9. A placebo-controlled, double-blind clinical trial to evaluate the efficacy of Imedeen® Time Perfection® for improving the appearance of photodamaged skin

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    Stephens TJ

    2016-03-01

    Full Text Available Thomas J Stephens,1 Monya L Sigler,1 James H Herndon Jr,2 Lisa Dispensa,3 Anne Le Moigne3 1Thomas J. Stephens and Associates, Inc., Richardson, TX, 2Dermatology Center of Dallas, Dallas, TX, 3Pfizer Consumer Healthcare, Madison, NJ, USA Objective: To assess the efficacy of Imedeen Time Perfection for improving the appearance and condition of photoaged skin in healthy women. Methods: This randomized, double-blind, placebo-controlled clinical trial enrolled healthy women, 35–60 years of age, with Fitzpatrick I–III and Glogau II–III skin types and mild-to-moderate facial fine lines/wrinkles. The eligible subjects were randomized to receive two tablets daily of either Imedeen Time Perfection (Imedeen or a matching placebo for 12 weeks. Efficacy assessments included investigator rating of 16 photoaging parameters (ie, global facial appearance and 15 individual facial parameters and the average of all parameters, instrumentation (ie, ultrasound dermal density, moisture level of the stratum corneum, transepidermal water loss, cutometry, and subjects' self-assessment. Differences in the mean change from baseline to week 12 values on these outcomes were compared between Imedeen and placebo using analysis of variance or a paired t-test. Results: Seventy-four subjects with primarily Fitzpatrick skin type III (78%–79% and Glogau type III (53%–58% completed the study (Imedeen: n=36; placebo: n=38. The mean difference in change from baseline to week 12 for global facial assessment significantly favored Imedeen over placebo (−0.52; P=0.0017. Additionally, the mean differences in the average of all facial photoaging parameters (−0.29, mottled hyperpigmentation (−0.25, tactile laxity (−0.24, dullness (−0.47, and tactile roughness (−0.62 significantly favored Imedeen over placebo (P≤0.05. Significantly greater increases in ultrasound dermal density (+11% vs +1%; P≤0.05 and stratum corneum moisturization (+30% vs +6%; P≤0.05 were also

  10. Short communication: Evaluation of vaginal discharge following treatment with a progesterone insert.

    Science.gov (United States)

    Fischer-Tenhagen, C; von Krueger, X; Heuwieser, W

    2012-08-01

    Yellowish discharge after application of intravaginal progesterone releasing inserts is frequently observed in cows. The objective of this study was to compare the bacteriological contamination of the vagina and uterus before and after a treatment with a progesterone insert in heifers. Forty-two Holstein heifers received a progesterone releasing insert [Eazi-Breed controlled internal drug release (CIDR) insert; Pfizer Animal Health, Berlin, Germany] for 7d. The protruding tail had been removed from half of the inserts (no tail group: n=21; tail group: n=21). Nine heifers from the tail group lost the insert within the 7-d treatment interval and were excluded. Heifers identified in estrus were artificially inseminated on d 9 or 10. Vaginal discharge was scored on a 4-point scale [vaginal discharge score (VDS) 0 to 3] and vaginal swabs were taken for bacteriological examination on d 0 and 7 and the day of artificial insemination (AI). Furthermore, cytological and bacteriological samples were obtained from the uterus on d 7 and the day of AI. On d 0, coliforms and Streptococcus spp. were found in vaginal swabs of 21 heifers (64%). On d 7, all heifers showed purulent vaginal discharge (VDS 2 to 3). The VDS was higher in the tail group compared with the no tail group. Arcanobacterium pyogenes, coliforms, and Streptococcus spp. were isolated from the vaginal swabs in 32 of 33 (96%) heifers on d 7. On the day of AI, VDS had improved to 0 or 1 in 96% of the heifers. However, A. pyogenes, coliforms, and Streptococcus spp. were still isolated in 17 of 33 (53%) heifers from the vagina and in 32 of 33 (96%) heifers from the endometrium. Endometrial cytology revealed polymorphonuclear neutrophils (PMN) in 11 heifers (6 to 32% PMN). Five samples exceeded the threshold of 5% PMN, and 2 samples exceeded the 10% PMN threshold, indicative of subclinical endometritis. In conclusion, pyogenic bacteria were found in the vagina and uterus on d 7 and the day of AI after intravaginal

  11. Tyrosine kinase receptor inhibitor-targeted combined chemotherapy for metastatic bladder cancer

    Directory of Open Access Journals (Sweden)

    Chia-Lun Wu

    2012-04-01

    Full Text Available Overexpression of hypoxia-inducible factor-1 alpha is noted during the invasive and metastatic process of transitional cell carcinoma. It will upregulate vascular endothelial growth factor (VEGF and drive proliferation, invasiveness, metastasis, and antiapoptotic ability of cancer cells. We proposed that tyrosine kinase receptor inhibitor, sunitinib malate—(Sutent; Pfizer Inc., Taiwan, combined with chemotherapeutic drug may present synergistic cytotoxic enhancement to transitional cell carcinoma cells with subsequent inhibition of their cellular behaviors, including proliferation, invasiveness, and metastatic activity. The contents of VEGF-A in mouse bladder tumor cells (MBT-2 and culture medium were detected by quantification-polymerase chain reaction and Western blot individually. The inhibitory concentrations of various chemotherapeutic drugs, sunitinib, and their combination treatment in MBT-2 were determined by 3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide (MTT assay. Microchamber transmembrane migration assay was applied in evaluation of the inhibitory effects of different dosages of sunitinib and combination treatment on tumor cells. The cell cycle and apoptosis were analyzed after combination therapy by flow cytometry. Variation in apoptotic pathway was elucidated by Western blot using specific antibodies with cleaved PARP and caspase-3. Metastatic animal model mimicked by tail vein injection of MBT-2 cells was used to evaluate the treatment efficiency in tumor weight and survival rate. The mRNA and protein level of VEGF-A in MBT-2 cells increased by 70% at 48 hours interval under hypoxia stress condition. In MTT assay, MBT-2 cells had shown the highest sensitivity to epirubicin. Sunitinib combined with epirubicin had shown a synergistic cytotoxic effect to MBT-2 cells. Sunitinib and its combination with epirubicin showed significant inhibition on MBT-2 cells migration in microchambers. G2/M phase arrest and

  12. Perspectives on future Alzheimer therapies: amyloid-β protofibrils - a new target for immunotherapy with BAN2401 in Alzheimer's disease.

    Science.gov (United States)

    Lannfelt, Lars; Möller, Christer; Basun, Hans; Osswald, Gunilla; Sehlin, Dag; Satlin, Andrew; Logovinsky, Veronika; Gellerfors, Pär

    2014-01-01

    The symptomatic drugs currently on the market for Alzheimer's disease (AD) have no effect on disease progression, and this creates a large unmet medical need. The type of drug that has developed most rapidly in the last decade is immunotherapy: vaccines and, especially, passive vaccination with monoclonal antibodies. Antibodies are attractive drugs as they can be made highly specific for their target and often with few side effects. Data from recent clinical AD trials indicate that a treatment effect by immunotherapy is possible, providing hope for a new generation of drugs. The first anti-amyloid-beta (anti-Aβ) vaccine developed by Elan, AN1792, was halted in phase 2 because of aseptic meningoencephalitis. However, in a follow-up study, patients with antibody response to the vaccine demonstrated reduced cognitive decline, supporting the hypothesis that Aβ immunotherapy may have clinically relevant effects. Bapineuzumab (Elan/Pfizer Inc./Johnson & Johnson), a monoclonal antibody targeting fibrillar Aβ, was stopped because the desired clinical effect was not seen. Solanezumab (Eli Lilly and Company) was developed to target soluble, monomeric Aβ. In two phase 3 studies, Solanezumab did not meet primary endpoints. When data from the two studies were pooled, a positive pattern emerged, revealing a significant slowing of cognitive decline in the subgroup of mild AD. The Arctic mutation has been shown to specifically increase the formation of soluble Aβ protofibrils, an Aβ species shown to be toxic to neurons and likely to be present in all cases of AD. A monoclonal antibody, mAb158, was developed to target Aβ protofibrils with high selectivity. It has at least a 1,000-fold higher selectivity for protofibrils as compared with monomers of Aβ, thus targeting the toxic species of the peptide. A humanized version of mAb158, BAN2401, has now entered a clinical phase 2b trial in a collaboration between BioArctic Neuroscience and Eisai without the safety concerns seen

  13. Real-life efficacy of pregabalin for the treatment of peripheral neuropathic pain in daily clinical practice in Denmark: the NEP-TUNE study

    Directory of Open Access Journals (Sweden)

    Crawford ME

    2016-05-01

    Full Text Available Michael E Crawford,1 Peter Bo Poulsen,2 Berit Schiøttz-Christensen,3 Andreas Habicht,4 Mette Strand,2 Flemming W Bach5 1Copenhagen City Pain Clinic, Copenhagen K, 2Pfizer Denmark ApS, Ballerup, 3Spine Center Southern Denmark, Lillebælt Hospital, Middelfart, 4Signifikans ApS, Vedbæk, 5Department of Neurology, Aalborg University Hospital, Aalborg, Denmark Objective: The aim of this study was to provide evidence regarding the real-life efficacy of pregabalin in the treatment of peripheral neuropathic pain (NeP in Denmark. Methods: In this prospective, observational, noninterventional study, pregabalin (Lyrica® was prescribed following usual clinical practice. Compared with baseline, the primary study end points after 3 months of observation were changes in 1 the average level of pain during the past week, 2 the worst level of pain during the past week, and 3 the least level of pain during the past week. The Wilcoxon signed-rank test was used to perform paired analyses, and a multivariate regression analysis investigated factors driving change in pain. Results: A total of 86 of the 128 patients included were regarded as efficacy evaluable (those completing 3 months of pregabalin treatment. Patients (59 years were long-time sufferers of peripheral NeP, and 38% of them had comorbidities. The majority had previously been treated with tricyclic antidepressants or gabapentin. The average dose of pregabalin was 81.5 mg/d at baseline and 240 mg/d after 3 months. A clinically and statistically significant improvement of 2.2 points in the average level of pain intensity was found after 3 months. The higher the pain intensity at baseline, the higher was the reduction of the pain score. Positive results were also found for pain-related sleep interference, patients’ global impression of change, quality of life, and work and productivity impairment. Twenty-one patients reported 28 adverse events. Conclusion: This real-life study indicates that for some

  14. Patient preference and ease of use for different coagulation factor VIII reconstitution device scenarios: a cross-sectional survey in five European countries

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    Cimino E

    2014-12-01

    Full Text Available Ernesto Cimino,1 Silvia Linari,2 Mara Malerba,3 Susan Halimeh,4 Francesca Biondo,5 Martina Westfeld5 1Dipartimento Medicina Clinica e Sperimentale, Universita’ degli Studi di Napoli Federico II, Naples, Italy; 2Agenzia per l’ Emofilia, AOU Careggi di Firenze, Florence, Italy; 3Fondazione Cà Granda Ospedale Maggiore Policlinico, Centro Emofilia e Trombosi “A Bianchi Bonomi”, Milan, Italy; 4CRC Coagulation Research Centre GmbH, Duisburg, Germany; 5Pfizer Italia, Rome, Italy Introduction: Hemophilia A treatment involves replacing the deficient coagulation factor VIII. This process may involve multiple steps that might create a barrier to adherence. A new dual-chamber syringe (DCS; FuseNGo® was recently introduced with the aim of simplifying reconstitution. Aim: This study aimed to identify factors associated with adult patients’ preferences for different coagulation factor VIII reconstitution systems and to test ease of use and patient preference for the DCS. Methods: A cross-sectional survey of adults with hemophilia A in five European countries was conducted; a subset of subjects also participated in a practical testing session of the DCS. Results: Among the 299 survey participants, the device scenario requiring the least equipment and reconstitution steps (the DCS received a median preference rating of 71 out of 100 (0 being “the least desirable” and 100 “the most desirable” rating. This was significantly higher than the other scenarios (the next highest achieved a median of 50 points; P<0.001. Participants would be more likely to use this device prophylactically (P<0.001. Among the 98 participants who tested the DCS, 57% preferred this device over their current device, 26% preferred their current device, and 17% had no preference. The DCS was rated as easier to use than current treatment devices (median score 9/10 versus 7/10 for current treatment, P=0.001. Conclusion: The survey indicates that the prefilled DCS, Fuse

  15. Tofacitinib for Psoriatic Arthritis in Patients with an Inadequate Response to TNF Inhibitors.

    Science.gov (United States)

    Gladman, Dafna; Rigby, William; Azevedo, Valderilio F; Behrens, Frank; Blanco, Ricardo; Kaszuba, Andrzej; Kudlacz, Elizabeth; Wang, Cunshan; Menon, Sujatha; Hendrikx, Thijs; Kanik, Keith S

    2017-10-19

    was more effective than placebo over 3 months in reducing disease activity. Adverse events were more frequent with tofacitinib than with placebo. (Funded by Pfizer; OPAL Beyond ClinicalTrials.gov number, NCT01882439 .).

  16. Reversibility of peripheral blood leukocyte phenotypic and functional changes after exposure to and withdrawal from tofacitinib, a Janus kinase inhibitor, in healthy volunteers.

    Science.gov (United States)

    Weinhold, Kent J; Bukowski, Jack F; Brennan, Todd V; Noveck, Robert J; Staats, Janet S; Lin, Liwen; Stempora, Linda; Hammond, Constance; Wouters, Ann; Mojcik, Christopher F; Cheng, John; Collinge, Mark; Jesson, Michael I; Hazra, Anasuya; Biswas, Pinaki; Lan, Shuping; Clark, James D; Hodge, Jennifer A

    2018-06-01

    . Copyright © 2018 Pfizer Inc. Published by Elsevier Inc. All rights reserved.

  17. Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis.

    Science.gov (United States)

    Sandborn, William J; Su, Chinyu; Sands, Bruce E; D'Haens, Geert R; Vermeire, Séverine; Schreiber, Stefan; Danese, Silvio; Feagan, Brian G; Reinisch, Walter; Niezychowski, Wojciech; Friedman, Gary; Lawendy, Nervin; Yu, Dahong; Woodworth, Deborah; Mukherjee, Arnab; Zhang, Haiying; Healey, Paul; Panés, Julian

    2017-05-04

    active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo. (Funded by Pfizer; OCTAVE Induction 1, OCTAVE Induction 2, and OCTAVE Sustain ClinicalTrials.gov numbers, NCT01465763 , NCT01458951 , and NCT01458574 , respectively.).

  18. Tofacitinib or Adalimumab versus Placebo for Psoriatic Arthritis.

    Science.gov (United States)

    Mease, Philip; Hall, Stephen; FitzGerald, Oliver; van der Heijde, Désirée; Merola, Joseph F; Avila-Zapata, Francisco; Cieślak, Dorota; Graham, Daniela; Wang, Cunshan; Menon, Sujatha; Hendrikx, Thijs; Kanik, Keith S

    2017-10-19

    infections, and four cases of herpes zoster in patients who received tofacitinib during the trial. The efficacy of tofacitinib was superior to that of placebo at month 3 in patients with psoriatic arthritis who had previously had an inadequate response to conventional synthetic DMARDs. Adverse events were more frequent with tofacitinib than with placebo. (Funded by Pfizer; OPAL Broaden ClinicalTrials.gov number, NCT01877668 .).

  19. Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial.

    Science.gov (United States)

    Fleischmann, Roy; Mysler, Eduardo; Hall, Stephen; Kivitz, Alan J; Moots, Robert J; Luo, Zhen; DeMasi, Ryan; Soma, Koshika; Zhang, Richard; Takiya, Liza; Tatulych, Svitlana; Mojcik, Christopher; Krishnaswami, Sriram; Menon, Sujatha; Smolen, Josef S

    2017-07-29

    [-14 to 3]) or tofacitinib and methotrexate (-8 [-16 to 1]). In total, 23 (6%) of 384 patients receiving tofacitinib monotherapy, 26 (7%) of 376 patients receiving tofacitinib plus methotrexate, and 36 (9%) of 386 patients receiving adalimumab plus methotrexate discontinued due to adverse events. Two (1%) of the 384 patients receiving tofacitinib monotherapy died. No new or unexpected safety issues were reported for either treatment in this study for up to 1 year. Tofacitinib and methotrexate combination therapy was non-inferior to adalimumab and methotrexate combination therapy in the treatment of rheumatoid arthritis in patients with an inadequate response to methotrexate in this trial. Tofacitinib monotherapy was not shown to be non-inferior to either combination. Pfizer Inc. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Consensus on Recording Deep Endometriosis Surgery: the CORDES statement.

    Science.gov (United States)

    Vanhie, A; Meuleman, C; Tomassetti, C; Timmerman, D; D'Hoore, A; Wolthuis, A; Van Cleynenbreugel, B; Dancet, E; Van den Broeck, U; Tsaltas, J; Renner, S P; Ebert, A D; Carmona, F; Abbott, J; Stepniewska, A; Taylor, H; Saridogan, E; Mueller, M; Keckstein, J; Pluchino, N; Janik, G; Zupi, E; Minelli, L; Cooper, M; Dunselman, G; Koh, C; Abrao, M S; Chapron, C; D'Hooghe, T

    2016-06-01

    recommendations presented here. This international expert consensus for standardized reporting of surgical treatment in women with DE, based on a systematic literature review and international consensus, can be used as a guideline to record and report surgical management of patients with DE and as a guideline to design, execute, interpret and compare clinical trials in this patient population. None of the authors received funding for the development of this paper. M.A. reports personal fees and non-financial support from Bayer Pharma outside the submitted work; H.T. reports a grant from Pfizer and personal fees for being on the advisory board of Perrigo, Abbvie, Allergan and SPD. N/A. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. The Zodiak workshop: an innovative model for teaching financial management through partnership with industry.

    Science.gov (United States)

    Lloyd, James W; Frawley, Suzanne L; Neer, Charles A; Merle, Christine; Goebel, Richard

    2004-01-01

    The National Commission on Veterinary Economic Issues (NCVEI) is working to enhance the non-technical skills, knowledge, aptitudes, and attitudes (SKAs) of veterinarians. This report describes the development of an innovative model for teaching the principles of financial management as they apply to the veterinary practice. Zodiak: The Game of Business Finance and Strategy is a "business literacy" game in which players work together in small teams (generally four people) to run a fictional multi-million-dollar company called Zodiak Industries for three "years" in order to learn principles of business finance and strategy. After finishing the 4.5-hour game, participants spend the rest of the workshop making the right "Connections"-exercises designed to connect what they have learned to business strategies, financial statements, and operational tactics drawn from veterinary practice. Issues addressed for the veterinary practice, with parallels drawn to Zodiak, included return on owner investment in a veterinary practice (vs. salary drawn by owner veterinarians); pricing (setting prices, price elasticity of demand, and relationships between volume, quality, and price); human resources and operations management as they relate to profitability and efficiency; cash flow and management of accounts receivable; and commonly used financial benchmarks. Workshop venues have included Michigan State University, The Ohio State University, the University of Illinois, and Purdue University. Financial and in-kind support were provided through partnership with Pharmacia Animal Health (now Pfizer Animal Health) and Hill's Pet Nutrition, Inc. Through course evaluations, participants generally rated the workshop high as an educational experience and indicated that the most important things learned were related to financial management (principles, terminology, and methods). The most enjoyable aspects of the workshop tended to be group discussions, teamwork, the dynamic

  2. Health Economic Data Requirements and Availability in the European Union: Results of a Survey Among 10 European Countries.

    Science.gov (United States)

    Skoupá, Jana; Annemans, Lieven; Hájek, Petr

    2014-09-01

    To compare data requirements and their availability for health economic (HE) evaluations in five countries in Central/Eastern Europe (CEE) (Poland, the Czech Republic, Slovakia, Hungary, and Romania) and five countries in Western Europe (WE) (the United Kingdom, France, Germany, The Netherlands, and Sweden). A questionnaire was developed and distributed to market access personnel from Pfizer who were asked to complete the questionnaire either from their own knowledge or with support of external experts. The questionnaire focused on the obligation to conduct HE assessment for reimbursement submissions, local HE guidelines, applied discount rates for future costs and effects, willingness-to-pay thresholds, and available data sources. HE is mandatory in all CEE and three WE participating countries for reimbursement applications of innovative drugs. Usually, cost-effectiveness analysis and budget-impact analyses are required. The preferred outcome of cost-effectiveness analysis is quality-adjusted-life years. In Romania, France, and the Czech Republic, guidelines could not be identified at the time of the survey. The applicant usually prepares HE evaluations; in Sweden, the United Kingdom, The Netherlands, and Poland, unlocked models have to be presented for scrutiny. Discount rates vary from 1.5% to 5%, and, usually, is the same for costs and outcomes (except in The Netherlands and Poland). Only the United Kingdom, Poland, and Slovakia have an explicit willingness-to-pay threshold. In Poland, it is based on the gross domestic product per capita, and in Slovakia, it is based on multiples of average monthly salary. Differences were found on data availability. In WE, data can be acquired easier than in CEE. Health insurance funds do not provide their data unless they were published. Patient registries are either not available in CEE or difficult to access, so applicants mostly rely on retrospective medical chart data, hospital information systems, or expert panels. We

  3. A randomized direct comparison of the pharmacokinetics and pharmacodynamics of apixaban and rivaroxaban

    Directory of Open Access Journals (Sweden)

    Frost C

    2014-11-01

    Full Text Available Charles Frost,1 Yan Song,1 Yu Chen Barrett,1 Jessie Wang,2 Janice Pursley,3 Rebecca A Boyd,4 Frank LaCreta1 1Exploratory Clinical and Translational Research, 2Exploratory Development Global Biometric Sciences, 3Analytical and Bioanalytical Development, Bristol-Myers Squibb Company, Princeton, NJ, USA; 4Global Innovative Pharma Business Clinical Pharmacology, Pfizer Inc., Groton, CT, USA Background: Currently, there are no direct comparisons of apixaban and rivaroxaban, two new oral direct factor Xa inhibitors approved for management of thromboembolic disorders. Objective: Compare the pharmacokinetics and anti-factor Xa activity (AXA of apixaban and rivaroxaban. Methods: In this randomized, open-label, two-period, two-treatment crossover study, healthy subjects (N=14 received apixaban 2.5 mg twice daily (BID and rivaroxaban 10 mg once daily (QD for 4 days with a ≥4.5-day washout. Plasma samples were obtained for pharmacokinetic and AXA assessments; parameters were calculated using noncompartmental methods. Results: Median time-to-maximum concentration was 2 hours for both compounds, and the mean half-life was 8.7 and 7.9 hours for apixaban and rivaroxaban, respectively. Daily exposure, the area under the curve (AUC(0–24, appeared similar for rivaroxaban (1,094 ng · h/mL and apixaban (935 ng · h/mL, whereas mean peak-to-trough plasma concentration ratio was 3.6-fold greater for rivaroxaban (16.9 than apixaban (4.7. Coefficient of variation for exposure parameters (AUC0–24, Cmax, Cmin was 20%–24% for apixaban versus 29%–46% for rivaroxaban. Peak AXA, AXA AUC(0–24, and AXA fluctuation were ~2.5-, 1.3-, and 3.5-fold higher for rivaroxaban than apixaban, respectively. Trough concentrations and AXA were lower for rivaroxaban (10 ng/mL and 0.17 IU/mL vs 17 ng/mL and 0.24 IU/mL for apixaban, respectively. Rivaroxaban exhibited a steeper concentration–AXA response (slope: 0.0172 IU/ng vs 0.0134 IU/ng for apixaban, P<0.0001. Conclusion

  4. Multiple-level stakeholder engagement in malaria clinical trials: addressing the challenges of conducting clinical research in resource-limited settings.

    Science.gov (United States)

    Mtove, George; Kimani, Joshua; Kisinza, William; Makenga, Geofrey; Mangesho, Peter; Duparc, Stephan; Nakalembe, Miriam; Phiri, Kamija S; Orrico, Russell; Rojo, Ricardo; Vandenbroucke, Pol

    2018-03-22

    Multinational clinical trials are logistically complex and require close coordination between various stakeholders. They must comply with global clinical standards and are accountable to multiple regulatory and ethical bodies. In resource-limited settings, it is challenging to understand how to apply global clinical standards to international, national, and local factors in clinical trials, making multiple-level stakeholder engagement an important element in the successful conduct of these clinical trials. During the planning and implementation of a large multinational clinical trial for intermittent preventive treatment of malaria in pregnancy in resource-limited areas of sub-Saharan Africa, we encountered numerous challenges, which required implementation of a range of engagement measures to ensure compliance with global clinical and regulatory standards. These challenges included coordination with ongoing global malaria efforts, heterogeneity in national regulatory structures, sub-optimal healthcare infrastructure, local practices and beliefs, and perspectives that view healthcare providers with undue trust or suspicion. In addition to engagement with international bodies, such as the World Health Organization, the Malaria in Pregnancy Consortium, the Steve Biko Centre for Bioethics, and the London School of Hygiene and Tropical Medicine, in order to address the challenges just described, Pfizer Inc. and Medicines for Malaria Venture (the "Sponsoring Entities" for these studies) and investigators liaised with national- and district-level stakeholders such as health ministers and regional/local community health workers. Community engagement measures undertaken by investigators included local meetings with community leaders to explain the research aims and answer questions and concerns voiced by the community. The investigators also engaged with family members of prospective trial participants in order to be sensitive to local practices and beliefs. Engagement

  5. Assessment of clinical effects and safety of an oral supplement based on marine protein, vitamin C, grape seed extract, zinc, and tomato extract in the improvement of visible signs of skin aging in men

    Directory of Open Access Journals (Sweden)

    Costa A

    2015-06-01

    Full Text Available Adilson Costa,1,2 Elisangela Samartin Pegas Pereira,1 Elvira Cancio Assumpção,1 Felipe Borba Calixto dos Santos,1 Fernanda Sayuri Ota,1 Margareth de Oliveira Pereira,1 Maria Carolina Fidelis,1 Raquel Fávaro,1 Stephanie Selma Barros Langen,1 Lúcia Helena Favaro de Arruda,1 Eva Nydal Abildgaard3 1Department of Dermatology, Pontifícia Universidade Católica de Campinas, Campinas, São Paulo, Brazil; 2KOLderma Clinical Trials Institute, Campinas, São Paulo, Brazil; 3Pfizer Consumer Healthcare, Nutritional Sciences, Copenhagen, Denmark Background: Skin aging is a natural process that may be aggravated by environmental factors. Topical products are the conventional means to combat aging; however, the use of oral supplements is on the rise to assist in the management of aged skin.Objective: The purpose of this study was to assess the effects and safety of an oral supplement containing (per tablet marine protein (105 mg, vitamin C (27 mg, grape seed extract (13.75 mg, zinc (2 mg, and tomato extract (14.38 mg in the improvement of skin aging in men.Methods: This single-center, open-label, quasi-experimental clinical study enrolled 47 male subjects, aged 30–45 years, with phototypes I–IV on the Fitzpatrick scale. Subjects received two tablets of the oral supplement for 180 consecutive days. Each subject served as their own control. Clinical assessments were made by medical personnel and by the subjects, respectively. Objective assessments were carried out through pH measurements, sebumetry, corneometry, ultrasound scanning, skin biopsies, and photographic images.Results: Forty-one subjects (87% completed the study. Clinical improvements on both investigator- and subject-rated outcomes were found for the following parameters: erythema, hydration, radiance, and overall appearance (P<0.05. The objective measurements in the facial skin showed significant improvements from baseline in skin hydration (P<0.05, dermal ultrasound density (P<0.001, and

  6. Treatments for chronic myeloid leukemia: a qualitative systematic review

    Directory of Open Access Journals (Sweden)

    Ferdin

    2012-08-01

    Full Text Available Roxanne Ferdinand,1 Stephen A Mitchell,2 Sarah Batson,2 Indra Tumur11Pfizer, Tadworth, UK; 2Abacus International, Bicester, UKBackground: Chronic myeloid leukemia (CML is a myeloproliferative disorder of blood stem cells. The tyrosine kinase inhibitor (TKI imatinib was the first targeted therapy licensed for patients with chronic-phase CML, and its introduction was associated with substantial improvements in response and survival compared with previous therapies. Clinical trial data are now available for the second-generation TKIs (nilotinib, dasatinib, and bosutinib in the first-, second-, and third-line settings. A qualitative systematic review was conducted to qualitatively compare the clinical effectiveness, safety, and effect on quality of life of TKIs for the management of chronic-, accelerated-, or blast-phase CML patients.Methods: Included studies were identified through a search of electronic databases in September 2011, relevant conference proceedings and the grey literature.Results: In the first-line setting, the long-term efficacy (up to 8 years of imatinib has been confirmed in a single randomized controlled trial (International Randomized Study of Interferon [IRIS]. All second-generation TKIs reported lower rates of transformation, and comparable or superior complete cytogenetic response (CCyR, major molecular response (MMR, and complete molecular response rates compared with imatinib by 2-year follow-up. Each of the second-generation TKIs was associated with a distinct adverse-event profile. Bosutinib was the only second-generation TKI to report quality-of-life data (no significant difference compared with imatinib treatment. Data in the second- and third-line setting confirmed the efficacy of the second-generation TKIs in either imatinib-resistant or -intolerant patients, as measured by CCyR and MMR rates.Conclusion: Data from first-line randomized controlled trials reporting up to 2-year follow-up indicate superior response

  7. Non-invasive assessment of the reproductive cycle in free-ranging female African elephants (Loxodonta africana) treated with a gonadotropin-releasing hormone (GnRH) vaccine for inducing anoestrus.

    Science.gov (United States)

    Benavides Valades, Gabriela; Ganswindt, Andre; Annandale, Henry; Schulman, Martin L; Bertschinger, Henk J

    2012-08-25

    In southern Africa, various options to manage elephant populations are being considered. Immunocontraception is considered to be the most ethically acceptable and logistically feasible method for control of smaller and confined populations. In this regard, the use of gonadotropin-releasing hormone (GnRH) vaccine has not been investigated in female elephants, although it has been reported to be safe and effective in several domestic and wildlife species. The aims of this study were to monitor the oestrous cycles of free-ranging African elephant cows using faecal progestagen metabolites and to evaluate the efficacy of a GnRH vaccine to induce anoestrus in treated cows. Between May 2009-June 2010, luteal activity of 12 elephant cows was monitored non-invasively using an enzyme immunoassay detecting faecal 5alpha-reduced pregnanes (faecal progestagen metabolites, FPM) on a private game reserve in South Africa. No bulls of breeding age were present on the reserve prior to and for the duration of the study. After a 3-month control period, 8 randomly-selected females were treated twice with 600 micrograms of GnRH vaccine (Improvac®, Pfizer Animal Health, Sandton, South Africa) 5-7 weeks apart. Four of these females had been treated previously with the porcine zona pellucida (pZP) vaccine for four years (2004-2007). All 12 monitored females (8 treated and 4 controls) showed signs of luteal activity as evidenced by FPM concentrations exceeding individual baseline values more than once. A total of 16 oestrous cycles could be identified in 8 cows with four of these within the 13 to 17 weeks range previously reported for captive African elephants. According to the FPM concentrations the GnRH vaccine was unable to induce anoestrus in the treated cows. Overall FPM levels in samples collected during the wet season (mean 4.03 micrograms/gram dry faeces) were significantly higher (Pelephants. These results indicate that irregular oestrous cycles occur amongst free

  8. Non-invasive assessment of the reproductive cycle in free-ranging female African elephants (Loxodonta africana treated with a gonadotropin-releasing hormone (GnRH vaccine for inducing anoestrus

    Directory of Open Access Journals (Sweden)

    Benavides Valades Gabriela

    2012-08-01

    Full Text Available Abstract Background In southern Africa, various options to manage elephant populations are being considered. Immunocontraception is considered to be the most ethically acceptable and logistically feasible method for control of smaller and confined populations. In this regard, the use of gonadotropin-releasing hormone (GnRH vaccine has not been investigated in female elephants, although it has been reported to be safe and effective in several domestic and wildlife species. The aims of this study were to monitor the oestrous cycles of free-ranging African elephant cows using faecal progestagen metabolites and to evaluate the efficacy of a GnRH vaccine to induce anoestrus in treated cows. Methods Between May 2009 - June 2010, luteal activity of 12 elephant cows was monitored non-invasively using an enzyme immunoassay detecting faecal 5alpha-reduced pregnanes (faecal progestagen metabolites, FPM on a private game reserve in South Africa. No bulls of breeding age were present on the reserve prior to and for the duration of the study. After a 3-month control period, 8 randomly-selected females were treated twice with 600 micrograms of GnRH vaccine (Improvac®, Pfizer Animal Health, Sandton, South Africa 5-7 weeks apart. Four of these females had been treated previously with the porcine zona pellucida (pZP vaccine for four years (2004-2007. Results All 12 monitored females (8 treated and 4 controls showed signs of luteal activity as evidenced by FPM concentrations exceeding individual baseline values more than once. A total of 16 oestrous cycles could be identified in 8 cows with four of these within the 13 to 17 weeks range previously reported for captive African elephants. According to the FPM concentrations the GnRH vaccine was unable to induce anoestrus in the treated cows. Overall FPM levels in samples collected during the wet season (mean 4.03 micrograms/gram dry faeces were significantly higher (P Conclusions The GnRH vaccination protocol failed

  9. Patient considerations in the management of menopausal symptoms: role of conjugated estrogens with bazedoxifene

    Directory of Open Access Journals (Sweden)

    Kagan R

    2016-04-01

    Full Text Available Risa Kagan,1,2 Steven R Goldstein,3 James H Pickar,4 Barry S Komm5 1Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, 2East Bay Physicians Medical Group, Berkeley, CA, 3Department of Obstetrics and Gynecology, New York University School of Medicine, 4Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, NY, 5Global Medical Affairs, Pfizer Inc., Collegeville, PA, USA Abstract: Menopausal symptoms (eg, hot flushes and vaginal symptoms are common, often bothersome, and can adversely impact women’s sexual functioning, relationships, and quality of life. Estrogen–progestin therapy was previously considered the standard care for hormone therapy (HT for managing these symptoms in nonhysterectomized women, but has a number of safety and tolerability concerns (eg, breast cancer, stroke, pulmonary embolism, breast pain/tenderness, and vaginal bleeding and its use has declined dramatically in the past decade since the release of the Women’s Health Initiative trial results. Conjugated estrogens paired with bazedoxifene (CE/BZA represent a newer progestin-free alternative to traditional HT for nonhysterectomized women. CE/BZA has demonstrated efficacy in reducing the frequency and severity of vasomotor symptoms and preventing loss of bone mineral density in postmenopausal women. CE/BZA provides an acceptable level of protection against endometrial hyperplasia and does not increase mammographic breast density. Compared with traditional estrogen–progestin therapy, it is associated with lower rates of breast pain/tenderness and vaginal bleeding. Patient-reported outcomes indicate that CE/BZA improves menopause-specific quality of life, sleep, some measures of sexual function (especially ease of lubrication, and treatment satisfaction. This review looks at the rationale for selection and combination of CE with BZA at the dose ratio in the approved product and provides

  10. An open-label, long-term study examining the safety and tolerability of pregabalin in Japanese patients with central neuropathic pain

    Directory of Open Access Journals (Sweden)

    Onouchi K

    2014-07-01

    Full Text Available Kenji Onouchi,1 Hiroaki Koga,2 Kazumasa Yokoyama,3 Tamotsu Yoshiyama4 1Aida Memorial Rehabilitation Hospital, Moriya, Japan; 2Kumamoto Rehabilitation Hospital, Kikuchi-Gun, Japan; 3Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan; 4Pfizer Japan Inc., Tokyo, Japan Purpose: Studies of pregabalin for the treatment of central neuropathic pain have been limited to double-blind trials of 4–17 weeks in duration. The purpose of this study was to assess the long-term safety and tolerability of pregabalin in Japanese patients with central neuropathic pain. The efficacy of pregabalin was also assessed as a secondary measure. Patients and methods: This was a 53-week, multicenter, open-label trial of pregabalin (150–600 mg/day in Japanese patients with central neuropathic pain due to spinal cord injury, multiple sclerosis, or cerebral stroke. Results: A total of 103 patients received pregabalin (post-stroke =60; spinal cord injury =38; and multiple sclerosis =5. A majority of patients (87.4% experienced one or more treatment-related adverse events, most commonly somnolence, weight gain, dizziness, or peripheral edema. The adverse event profile was similar to that seen in other indications of pregabalin. Most treatment-related adverse events were mild (89.1% or moderate (9.2% in intensity. Pregabalin treatment improved total score, sensory pain, affective pain, visual analog scale (VAS, and present pain intensity scores on the Short-Form McGill Pain Questionnaire (SF-MPQ and ten-item modified Brief Pain Inventory (mBPI-10 total score at endpoint compared with baseline. Improvements in SF-MPQ VAS and mBPI-10 total scores were evident in all patient subpopulations. Mean changes from baseline in SF-MPQ VAS and mBPI-10 scores at endpoint were –20.1 and –1.4, respectively. Conclusion: These findings demonstrate that pregabalin is generally well tolerated and provides sustained efficacy over a 53-week treatment period in

  11. Antimicrobial resistance patterns of colonizing Streptococcus pneumoniae among young child-mother pairs in the rural highlands of the Peruvian Andes

    Science.gov (United States)

    Howard, Leigh; Edwards, Kathryn; Griffin, Marie; Gil, Ana; Minaya, Gina; Mercado, Erik; Ochoa, Theresa; Lanata, Claudio; Grijalva, Carlos G

    2017-01-01

    tetracyclines was common despite very little reported use of these antibiotics in people. Additional studies should evaluate whether this high prevalence of resistance is a result of local prescribing practices or unintentional environmental exposures. ADDIN EN.REFLIST Disclosures K. Edwards, Novartis: Grant Investigator, Research grant. M. Griffin, MedImmune: Grant Investigator, Grant recipient. C. Lanata, Takeda: Scientific Advisor, Consulting fee. C. G. Grijalva, Pfizer: Consultant, Consulting fee.

  12. Erectile function and assessments of erection hardness correlate positively with measures of emotional well-being, sexual satisfaction, and treatment satisfaction in men with erectile dysfunction treated with sildenafil citrate (Viagra).

    Science.gov (United States)

    Montorsi, Francesco; Padma-Nathan, Harin; Glina, Sidney

    2006-09-01

    We aimed to determine whether erectile function (EF) and assessments of erection hardness correlate positively with measures of psychosocial outcomes (ie, emotional well-being, sexual satisfaction, and satisfaction with erectile dysfunction [ED] treatment) in men treated with sildenafil citrate (Viagra; Pfizer Inc, New York, NY). Data were collected from 33 worldwide phase 2, 3, and 4 sildenafil clinical trials, which included almost 10,000 men with ED. Most of these trials were randomized, double-blind, and placebo-controlled (n = 27) and were undertaken to assess doses of 50 mg adjustable to 25 mg or 100 mg, depending on efficacy and tolerability (n = 32). Doses were taken approximately 1 hour before anticipated sexual activity but not more often than once daily. EF was assessed with use of the EF domain of the International Index of Erectile Function (IIEF) and with assessments of erection hardness (Erection Hardness Grading Scale [EHGS] and IIEF Q2 [the frequency of erections hard enough for penetration]). Change (baseline to end point) in emotional well-being in men treated for ED was assessed with the Self-Esteem and Relationship (SEAR) questionnaire, which consisted of the Confidence domain (ie, the Self-Esteem subscale and Overall Relationship subscale) and the Sexual Relationship domain. End point treatment satisfaction (overall, speed of onset, and duration of action) was assessed with the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS). The IIEF was used to assess change and end point sexual satisfaction by means of the Intercourse Satisfaction domain, Q7 (frequency of satisfactory sexual intercourse), and the Overall Satisfaction domain (ie, Q13, satisfaction with sex life, and Q14, satisfaction with sexual relationship). In men treated with sildenafil for ED, scores for measures of EF (IIEF EF domain, IIEF Q2) and the percentage of erections graded completely hard and fully rigid (EHGS grade 4) correlated positively with scores for

  13. Safety, pharmacokinetics, and preliminary activity of the anti-IGF-1R antibody figitumumab (CP-751,871) in patients with sarcoma and Ewing's sarcoma: a phase 1 expansion cohort study.

    Science.gov (United States)

    Olmos, David; Postel-Vinay, Sophie; Molife, L Rhoda; Okuno, Scott H; Schuetze, Scott M; Paccagnella, M Luisa; Batzel, Gretchen N; Yin, Donghua; Pritchard-Jones, Kathryn; Judson, Ian; Worden, Francis P; Gualberto, Antonio; Scurr, Michelle; de Bono, Johann S; Haluska, Paul

    2010-02-01

    synovial sarcoma, and one with fibrosarcoma) lasting 4 months or longer. Figitumumab is well tolerated and has antitumour activity in Ewing's sarcoma, warranting further investigation in this disease. Pfizer Global Research and Development. Copyright 2010 Elsevier Ltd. All rights reserved.

  14. Cognitive and neuroimaging features and brain β-amyloidosis in individuals at risk of Alzheimer's disease (INSIGHT-preAD): a longitudinal observational study.

    Science.gov (United States)

    Dubois, Bruno; Epelbaum, Stephane; Nyasse, Francis; Bakardjian, Hovagim; Gagliardi, Geoffroy; Uspenskaya, Olga; Houot, Marion; Lista, Simone; Cacciamani, Federica; Potier, Marie-Claude; Bertrand, Anne; Lamari, Foudil; Benali, Habib; Mangin, Jean-François; Colliot, Olivier; Genthon, Remy; Habert, Marie-Odile; Hampel, Harald

    2018-04-01

    deposition and the remainder did not. The amyloid β subgroups did not differ for any psychobehavioural, cognitive, actigraphy, and structural and functional neuroimaging results after adjustment for age, sex, and level of education More participants positive for amyloid β deposition had the APOE ε4 allele (33 [38%] vs 29 [13%], pCerveau et de la Moelle Epinière (IHU-A-ICM), Ministry of Research, Fondation Plan Alzheimer, Pfizer, and Avid. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Patterns of Adherence to Oral Atypical Antipsychotics Among Patients Diagnosed with Schizophrenia.

    Science.gov (United States)

    MacEwan, Joanna P; Forma, Felicia M; Shafrin, Jason; Hatch, Ainslie; Lakdawalla, Darius N; Lindenmayer, Jean-Pierre

    2016-11-01

    abuse (OR = 1.46; 95% CI = 1.26-1.66; P aged 35-54 years (OR = 0.66; 95% CI = 0.46-0.85; P different groups may warrant different types of clinical interventions to prevent hospitalizations, longer hospital stays, and increased clinical complexity. For example, clinicians may consider regular home visits, assertive community treatment, and other related interventions for patients at high risk of immediate discontinuation. Health plans should consider supplementing claims-based adherence measures with new technologies that are able to track patient adherence patterns over time. Otsuka Pharmaceutical Development & Commercialization provided support for this research. MacEwan and Shafrin are employees of Precision Health Economics, which was contracted by Otsuka Pharmaceutical Development & Commercialization to conduct this study. Lakdawalla is the Chief Scientific Officer and a founding partner of Precision Health Economics. Forma is an employee of Otsuka Pharmaceutical Development & Commercialization. Hatch is a former employee of Otsuka Pharmaceutical Development & Commercialization and is a current employee of ODH, Inc. Lindenmayer has received grant/research support from Janssen, Lilly, AstraZeneca, Johnson & Johnson, Pfizer, BMS, Otsuka, Dainippon, and Roche and is a consultant for Janssen, Lilly, Merck, Shire, and Lundbeck. Portions of this study were presented as a poster at the American Society of Clinical Psychopharmacology Annual Meeting in Miami Beach, Florida; June 23, 2015; and at the 28th Annual U.S. Psychiatric and Mental Health Congress; San Diego, California; September 12, 2015. Study concept and design were contributed by Forma, Ladkawalla, MacEwan, and Shafrin, along with Hatch and Lindenmayer. MacEwan, Shafrin, Forma, and Lakdawalla collected the data, along with Hatch and Lindenmayer. Data interpretation was performed by Hatch, Lindenmayer, MacEwan, and Shafrin, assisted by Forma and Lakdawalla. The manuscript was written and revised by MacEwan, Forma

  16. Crizotinib in patients with advanced, inoperable inflammatory myofibroblastic tumours with and without anaplastic lymphoma kinase gene alterations (European Organisation for Research and Treatment of Cancer 90101 CREATE): a multicentre, single-drug, prospective, non-randomised phase 2 trial.

    Science.gov (United States)

    Schöffski, Patrick; Sufliarsky, Jozef; Gelderblom, Hans; Blay, Jean-Yves; Strauss, Sandra J; Stacchiotti, Silvia; Rutkowski, Piotr; Lindner, Lars H; Leahy, Michael G; Italiano, Antoine; Isambert, Nicolas; Debiec-Rychter, Maria; Sciot, Raf; Van Cann, Thomas; Marréaud, Sandrine; Nzokirantevye, Axelle; Collette, Sandra; Wozniak, Agnieszka

    2018-06-01

    an objective response (ie, a complete or partial response) as per RECIST 1.1, with response confirmation assessed by the local investigator every other cycle. Activity and safety endpoints were analysed in the per-protocol population. This trial is registered with ClinicalTrials.gov, number NCT01524926. Between Oct 3, 2012, and April 12, 2017, we recruited and treated 20 eligible participants, 19 of whom were assessable for the primary endpoint. Median follow-up was 863 days (IQR 358-1304). Six of 12 ALK-positive patients (50%, 95% CI 21·1-78·9) and one of seven ALK-negative patients (14%, 0·0-57·9) achieved an objective response. The most common treatment-related adverse events in the 20 participants were nausea (11 [55%]), fatigue (9 [45%]), blurred vision (nine [45%]), vomiting (seven [35%]), and diarrhoea (seven [35%]). Eight serious adverse events occurred in five patients: pneumonia, fever of unknown cause, a heart attack with increased creatinine and possible sepsis, an abdominal abscess with acute renal insufficiency, and a QT prolongation. With 50% of participants with ALK-positive tumours achieving an objective response, crizotinib met the prespecified criteria for success in this trial. The results presented here support the rationale for inhibiting ALK in patients with IMFT. Crizotinib could be considered as the standard of care for patients with locally advanced or metastatic ALK-positive IMFT who do not qualify for curative surgery. The European Organisation for Research and Treatment of Cancer and Pfizer. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Presence of human papillomavirus in semen in relation to semen quality.

    Science.gov (United States)

    Luttmer, Roosmarijn; Dijkstra, Maaike G; Snijders, Peter J F; Hompes, Peter G A; Pronk, Divera T M; Hubeek, Isabelle; Berkhof, Johannes; Heideman, Daniëlle A M; Meijer, Chris J L M

    2016-02-01

    on the speakers bureau of Qiagen and has been a consultant for Roche, DDL Diagnostic Laboratory, GlaxoSmithKline and Merck. D.A.M.H. has been member of the scientific advisory boards of Amgen and Pfizer, and has been on the speakers bureau of Hologic/Gen-Probe. C.J.L.M.M. has been on the speakers bureau of GlaxoSmithKline, Qiagen, Merck, Roche, Menarini and Seegene, has served occasionally on the scientific advisory board of GlaxoSmithKline, Qiagen, Merck, Roche and Genticel, and has occasionally been a consultant for Qiagen. Formerly, C.J.L.M.M. was a minority shareholder of Delphi Biosciences, which bankrupted in 2014. C.J.L.M.M. is a minority shareholder of Diassay B.V. P.J.F.S., D.A.M.H. and C.J.L.M.M. have minority stake in Self-Screen B.V., a spin-off company of VU University Medical Center. R.L., M.G.D., P.G.A.H., D.T.M.P., and I.H. do not have any conflicts of interest to disclose. Not applicable. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Neo-angiogenesis metabolic biomarker of tumor-genesis tracking by infrared joystick contact imaging in personalized homecare system

    Science.gov (United States)

    Szu, Harold; Hoekstra, Philip; Landa, Joseph; Vydelingum, Nadarajen A.

    2014-05-01

    We describe an strong>affordable, harmless, and administrative (AHA) metabolic biomarker (MBM)strong> for homecare cancer screening. It may save hundreds of thousands of women's and thousands of men's lives every year from breast cancer and melanoma. The goal is to increase the specificity ofstrong> infrared (IR)strong> imagery to reduce the strong>false alarm rate (FAR). strong>The patient's hands are immersed in icy cold water, about 11oC, for 30 seconds. We then compare two IR images, taken before and after the cold stimulus, and the difference reveals an enhanced signal and noise ratio (SNR) at tumorigenesis sites since the contraction of capillaries under cold challenge is natural to healthy capillaries, except those newly built capillaries during angiogenesis (Folkman, Nature 1995). Concomitant with the genome and the phenome (molecular signaling by phosphor-mediate protein causing inflammation by strong>platelet activating factor (PAF)strong> that transform cells from benign to malignant is the amplification of strong>nitric oxide (NO)strong> syntheses, a short-lived reactive oxygen species (ROS) that dilates regional blood vessels; superseding normal autonomic nervous system regulation. A rapidly growing tumor site might implicate accumulation of strong>ROSstrong>, for which strong>NOstrong> can rapidly stretch the capillary bed system usually having thinning muscular lining known as strong>Neo-Angiogenesis (NA)strong> that could behave like strong>Leaky In-situ Faucet Effect (LIFE)strong> in response to cold challenge. To emphasize the state of art knowledge of strong>NAstrong>, we mentioned in passing the first generation of an anticapillary growth drug, strong>Avastinstrong> by Genetech; it is an antibody protein that is injected for metastasis, while the second generation drug; strong>Sorafenibstrong> by Bayers (2001) and strong>Sutentstrong> by Pfizer (2000) both target molecular signaling loci to block receptor associated tyrosine kinase induced

  19. Burden of illness associated with painful diabetic peripheral neuropathy among adults seeking treatment in the US: results from a retrospective chart review and cross-sectional survey

    Directory of Open Access Journals (Sweden)

    Sadosky A

    2013-02-01

    Full Text Available Alesia Sadosky,1 Caroline Schaefer,2 Rachael Mann,3 Felicia Bergstrom,2 Rebecca Baik,2 Bruce Parsons,1 Srinivas Nalamachu,4 Edward Nieshoff,5 Brett R Stacey,6 Alan Anschel,7 Michael Tuchman81Pfizer Inc, New York, NY, 2Covance Market Access Services Inc, Gaithersburg, MD, 3Covance Market Access Services Inc, San Diego, CA, 4International Clinical Research Institute, Overland Park, KS, 5Rehabilitation Institute of Michigan/Wayne State University, Detroit, MI, 6Oregon Health and Science University, Portland, OR, 7Rehabilitation Institute of Chicago, Chicago, IL, 8Palm Beach Neurological Center, Palm Beach Gardens, FL, USABackground: The purpose of this study was to characterize the burden of illness among adult subjects with painful diabetic peripheral neuropathy (pDPN seeking treatment in the US.Methods: This observational study recruited 112 subjects with pDPN during routine visits from general practitioner and specialist sites. Subjects completed a one-time questionnaire, which included demographics, symptom duration, health care resource use, out-of-pocket costs, employment status, and validated measures that assessed pain, functioning, sleep, anxiety and depression, health status, and productivity. Investigators completed a case report form based on a 6-month retrospective chart review to capture clinical information, pDPN-related treatments, and other pDPN-related health care resource use over the past 6 months. Annualized costs were extrapolated based on reported 6-month health care resource use.Results: The mean age of the subjects was 61.1 years, 52.7% were female, and 17.9% were in paid employment. The most common comorbid conditions were sleep disturbance/insomnia (43.8%, depressive symptoms (41.1%, and anxiety (35.7%. The mean pain severity score was 5.2 (0–10 scale, and 79.5% reported moderate or severe pain. The mean pain interference with function score was 5.0 (0–10 scale overall, with 2.0 among mild, 5.1 among moderate, and 7

  20. Carboxyl-modified single-wall carbon nanotubes improve bone tissue formation in vitro and repair in an in vivo rat model

    Directory of Open Access Journals (Sweden)

    Barrientos-Durán A

    2014-09-01

    Full Text Available Antonio Barrientos-Durán,1,5,* Ellen M Carpenter,2 Nicole I zur Nieden,3 Theodore I Malinin,4 Juan Carlos Rodríguez-Manzaneque,5 Laura P Zanello1,* 1Department of Biochemistry, University of California Riverside, Riverside, CA, USA; 2Department of Psychiatry and Biobehavioral Sciences, UCLA School of Medicine, South Los Angeles, CA, USA; 3Department of Cell Biology and Neuroscience, Stem Cell Center, College of Natural and Agricultural Sciences, University of California Riverside, Riverside, CA, USA; 4Tissue Bank, Department of Orthopedics, University of Miami Miller School of Medicine, Miami, FL, USA; 5Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (GENYO, Granada, Spain *These authors contributed equally to this workAbstract: The clinical management of bone defects caused by trauma or nonunion fractures remains a challenge in orthopedic practice due to the poor integration and biocompatibility properties of the scaffold or implant material. In the current work, the osteogenic properties of carboxyl-modified single-walled carbon nanotubes (COOH–SWCNTs were investigated in vivo and in vitro. When human preosteoblasts and murine embryonic stem cells were cultured on coverslips sprayed with COOH–SWCNTs, accelerated osteogenic differentiation was manifested by increased expression of classical bone marker genes and an increase in the secretion of osteocalcin, in addition to prior mineralization of the extracellular matrix. These results predicated COOH–SWCNTs’ use to further promote osteogenic differentiation in vivo. In contrast, both cell lines had difficulties adhering to multi-walled carbon nanotube-based scaffolds, as shown by scanning electron microscopy. While a suspension of SWCNTs caused cytotoxicity in both cell lines at levels >20 µg/mL, these levels were never achieved by release from sprayed SWCNTs, warranting the approach taken. In vivo, human allografts formed by the

  1. Health Care Resource Utilization and Costs in Patients with Chronic Myeloid Leukemia with Better Adherence to Tyrosine Kinase Inhibitors and Increased Molecular Monitoring Frequency.

    Science.gov (United States)

    Latremouille-Viau, Dominick; Guerin, Annie; Gagnon-Sanschagrin, Patrick; Dea, Katherine; Cohen, Benjamin G; Joseph, George J

    2017-02-01

    and medical service costs. Managed care initiatives to increase qPCR test frequency and TKI adherence might benefit from an enhanced reduction because of the interaction between both factors. This study was funded by Novartis Pharmaceuticals, which was involved in all stages of the study and in the decision to submit the report for publication. Latremouille-Viau, Guerin, Gagnon-Sanschagrin, and Dea are employees of Analysis Group, which received consulting fees from Novartis Pharmaceuticals for work on this study. Joseph is an employee of Novartis Pharmaceuticals and owns stock in Amgen and Pfizer. Cohen was an employee of Novartis Pharmaceuticals at the time of this study. Portions of this study were presented online (beginning May 20, 2016) as part of the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois, on June 3-7, 2016, and as a poster at the American Society of Hematology (ASH) Annual Meeting in San Diego, California, on December 3-6, 2016. Study concept and design were contributed by Latremouille-Viau and Guerin, along with the other authors. Gagnon-Sanschagrin and Dea took the lead in data collection, assisted by the other authors, and data interpretation was performed by Cohen and Joseph, along with the other authors. The manuscript was written by Latremouille-Viau, along with the other authors, and revised by Joseph, along with the other authors.

  2. BICLUSTERING METHODS FOR RE-ORDERING DATA MATRICES IN SYSTEMS BIOLOGY, DRUG DISCOVERY AND TOXICOLOGY

    Directory of Open Access Journals (Sweden)

    Christodoulos A. Floudas

    2010-12-01

    substituent reordering as a special high-dimensional rearrangement clustering problem, eliminating the need for functional approximation and enhancing computational efficiency [4, 5]. Deterministic optimization approaches based on mixed-integer linear programming can provide guaranteed convergence to the optimal substituent ordering. The proposed approach is demonstrated on a sparse data matrix (about 29% dense of inhibition values for 14,043 unknown compounds provided by Pfizer Inc. It is shown that an iterative synthesis strategy is able to uncover a significant percentage of the lead molecules while using only a fraction of total compound library, even when starting from a mere 3\\% of the total library space. In the third part of the presentation, we combine the strengths of integer linear optimization and machine learning to predict in vivo toxicities for a library of pesticide chemicals using only in vitro data. Our approach utilizes a biclustering method based on iterative optimal re-ordering [1,2] to identify biclusters corresponding to subsets of chemicals that have similar responses over distinct subsets of the in vitro assays. This enables us to determine subsets of experimental assays that are most likely to be correlated with toxicity, according to the in vivo data set. An optimal method based on integer linear optimization (ILP for re-ordering sparse data matrices [3] is also applied to the in vivo dataset (21.3% sparse in order to cluster endpoints that have similar lowest effect level (LEL values, where it is observed that endpoints are grouped according to similar physiological attributes. Based upon the clustering results of the in vitro and in vivo data sets, logistic regression is then utilized to (a learn the correlation between the subsets of in vitro data and the in vivo responses, and (b subsequently predict the toxicity signatures of the chemicals. Our approach aims to find the highest prediction accuracy using the minimum number of in vitro

  3. Pregabalin versus SSRIs and SNRIs in benzodiazepine-refractory outpatients with generalized anxiety disorder: a post hoc cost-effectiveness analysis in usual medical practice in Spain

    Directory of Open Access Journals (Sweden)

    De Salas-Cansado M

    2012-06-01

    Full Text Available Marina De Salas-Cansado,1 José M Olivares,2 Enrique Álvarez,3 Jose L Carrasco,4 Andoni Barrueta,5 Javier Rejas,51Trial Form Support Spain, Madrid; 2Department of Psychiatry, Hospital Meixoeiro, Complejo Hospitalario Universitario, Vigo; 3Department of Psychiatry, Hospital de la Santa Creu i San Pau, Barcelona; 4Department of Psychiatry, Hospital Clínico San Carlos, Madrid; 5Health Outcomes Research Department, Medical Unit, Pfizer Spain, Alcobendas, Madrid, SpainBackground: Generalized anxiety disorder (GAD is a prevalent health condition which seriously affects both patient quality of life and the National Health System. The aim of this research was to carry out a post hoc cost-effectiveness analysis of the effect of pregabalin versus selective serotonin reuptake inhibitors (SSRIs/serotonin norepinephrine reuptake inhibitors (SNRIs in treated benzodiazepine-refractory outpatients with GAD.Methods: This post hoc cost-effectiveness analysis used secondary data extracted from the 6-month cohort, prospective, noninterventional ADAN study, which was conducted to ascertain the cost of illness in GAD subjects diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. Benzodiazepine-refractory subjects were those who claimed persistent symptoms of anxiety and showed a suboptimal response (Hamilton Anxiety Rating Scale ≥16 to benzodiazepines, alone or in combination, over 6 months. Patients could switch to pregabalin (as monotherapy or addon or to an SSRI or SNRI, alone or in combination. Effectiveness was expressed as quality-adjusted life years gained, and the perspective was that of the National Health System in the year 2008. A sensitivity analysis was performed using bootstrapping techniques (10,000 resamples were obtained in order to obtain a cost-effectiveness plane and a corresponding acceptability curve.Results: A total of 282 subjects (mean Hamilton Anxiety Rating Scale score 25.8 were

  4. A Bivalent Meningococcal B Vaccine in Adolescents and Young Adults.

    Science.gov (United States)

    Ostergaard, Lars; Vesikari, Timo; Absalon, Judith; Beeslaar, Johannes; Ward, Brian J; Senders, Shelly; Eiden, Joseph J; Jansen, Kathrin U; Anderson, Annaliesa S; York, Laura J; Jones, Thomas R; Harris, Shannon L; O'Neill, Robert; Radley, David; Maansson, Roger; Prégaldien, Jean-Louis; Ginis, John; Staerke, Nina B; Perez, John L

    2017-12-14

    B-FHbp reported mild or moderate pain at the vaccination site. MenB-FHbp elicited bactericidal responses against diverse meningococcal B strains after doses 2 and 3 and was associated with more reactions at the injection site than the hepatitis A virus vaccine and saline. (Funded by Pfizer; ClinicalTrials.gov numbers, NCT01830855 and NCT01352845 ).

  5. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial.

    Science.gov (United States)

    Shaw, Alice T; Felip, Enriqueta; Bauer, Todd M; Besse, Benjamin; Navarro, Alejandro; Postel-Vinay, Sophie; Gainor, Justin F; Johnson, Melissa; Dietrich, Jorg; James, Leonard P; Clancy, Jill S; Chen, Joseph; Martini, Jean-François; Abbattista, Antonello; Solomon, Benjamin J

    2017-12-01

    -related adverse events among the 54 patients were hypercholesterolaemia (39 [72%] of 54 patients), hypertriglyceridaemia (21 [39%] of 54 patients), peripheral neuropathy (21 [39%] of 54 patients), and peripheral oedema (21 [39%] of 54 patients). One dose-limiting toxicity occurred at 200 mg (the patient did not take at least 16 of 21 prescribed total daily doses in cycle 1 because of toxicities attributable to study drug, which were grade 2 neurocognitive adverse events comprising slowed speech and mentation and word-finding difficulty). No maximum tolerated dose was identified. The recommended phase 2 dose was selected as 100 mg once daily. For ALK-positive patients, the proportion of patients who achieved an objective response was 19 (46%) of 41 patients (95% CI 31-63); for those who had received two or more TKIs, the proportion of patients with an objective response was 11 (42%) of 26 patients (23-63). In ROS1-positive patients, including seven crizotinib-pretreated patients, an objective response was achieved by six (50%) of 12 patients (95% CI 21-79). In this phase 1, dose-escalation study, lorlatinib showed both systemic and intracranial activity in patients with advanced ALK-positive or ROS1-positive NSCLC, most of whom had CNS metastases and had previously had two or more TKI treatments fail. Therefore, lorlatinib might be an effective therapeutic strategy for patients with ALK-positive NSCLC who have become resistant to currently available TKIs, including second-generation ALK TKIs, and is being investigated in a phase 3 randomised controlled trial comparing lorlatinib to crizotinib (ClinicalTrials.gov, NCT03052608). Pfizer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Adalimumab, etanercept and ustekinumab for treating plaque psoriasis in children and young people: systematic review and economic evaluation.

    Science.gov (United States)

    Duarte, Ana; Mebrahtu, Teumzghi; Goncalves, Pedro Saramago; Harden, Melissa; Murphy, Ruth; Palmer, Stephen; Woolacott, Nerys; Rodgers, Mark; Rothery, Claire

    2017-11-01

    Psoriasis is a chronic inflammatory disease that predominantly affects the skin. Adalimumab (HUMIRA ® , AbbVie, Maidenhead, UK), etanercept (Enbrel ® , Pfizer, New York, NY, USA) and ustekinumab (STELARA ® , Janssen Biotech, Inc., Titusville, NJ, USA) are the three biological treatments currently licensed for psoriasis in children. To determine the clinical effectiveness and cost-effectiveness of adalimumab, etanercept and ustekinumab within their respective licensed indications for the treatment of plaque psoriasis in children and young people. Searches of the literature and regulatory sources, contact with European psoriasis registries, company submissions and clinical study reports from manufacturers, and previous National Institute for Health and Care Excellence (NICE) technology appraisal documentation. Included studies were summarised and subjected to detailed critical appraisal. A network meta-analysis incorporating adult data was developed to connect the effectiveness data in children and young people and populate a de novo decision-analytic model. The model estimated the cost-effectiveness of adalimumab, etanercept and ustekinumab compared with each other and with either methotrexate or best supportive care (BSC), depending on the position of the intervention in the management pathway. Of the 2386 non-duplicate records identified, nine studies (one randomised controlled trial for each drug plus six observational studies) were included in the review of clinical effectiveness and safety. Etanercept and ustekinumab resulted in significantly greater improvements in psoriasis symptoms than placebo at 12 weeks' follow-up. The magnitude and persistence of the effects beyond 12 weeks is less certain. Adalimumab resulted in significantly greater improvements in psoriasis symptoms than methotrexate for some but not all measures at 16 weeks. Quality-of-life benefits were inconsistent across different measures. There was limited evidence of excess short

  7. Medicinal chemistry of antischistosomal drugs: Praziquantel and oxamniquine.

    Science.gov (United States)

    da Silva, Vinícius Barros Ribeiro; Campos, Bruna Rafaella Koresch Leiva; de Oliveira, Jamerson Ferreira; Decout, Jean-Luc; do Carmo Alves de Lima, Maria

    2017-07-01

    Neglected tropical diseases (NTDs) are a group of diseases that, besides prevailing in poverty conditions, contribute to the maintenance of social inequality, being a strong barrier to a country development. Schistosomiasis, a NTD, is a tropical and subtropical disease caused by the trematode Schistosoma mansoni (Africa, Middle East, Caribbean, Brazil, Venezuela, Suriname), japonicum (China, Indonesia, the Philippines), mekongi (several districts of Cambodia and the Lao People's Democratic Republic), intercalatum and guianensis (areas of tropical rainforests in Central Africa) and hematobium (Middle East Africa, Corsica, France) whose adult forms inhabit the mesenteric vessels of the host, while the intermediate forms are found in the aquatic gastropod snails of the genus Biomphalaria. Currently, praziquantel (PZQ) is the first line drug chosen for the treatment of schistosomiasis according to the World Health Organization (WHO) Model List of Essential Medicines, 2015. PZQ chemotherapy is considered to be the most important development for decades in the treatment of schistosomiasis. Beside the PZQ, oxamniquine (OXA) has been first described in 1969 and launched in Brazil by Pfizer under the name of Mansil® for oral administration. It has a lower cost when compared to PZQ, being active in the intestinal and hepatosplenic infections caused exclusively by S. mansoni, single species in Brazil. Both PZQ and OXA have limitations, as low efficacy in the treatment of acute schistosomiasis, low activity against S. mansoni in immature stages and resistance or tolerance, which is the reason why further research are still necessary for the development of a second generation of antischistosomal drugs. For the development of new PZQ analogs, three main strategies can be adopted: (a) synthesis and evaluation of PZQ analogues; (b) rational design of new pharmacophores; (c) discovery of new active compounds from screening programs on a large scale. Such (b) approach is difficult

  8. Paying for Cures: How Can We Afford It? Managed Care Pharmacy Stakeholder Perceptions of Policy Options to Address Affordability of Prescription Drugs.

    Science.gov (United States)

    Yeung, Kai; Suh, Kangho; Basu, Anirban; Garrison, Louis P; Bansal, Aasthaa; Carlson, Josh J

    2017-10-01

    policy. As high-cost curative drugs reach the market, managed care stakeholders need information from a balanced education source regarding alternative policies to address affordability. We found that after the AMCP CPE session, risk-sharing payments over time and HealthCoin were the most favorable options. No funding was provided for this research. Carlson reports consulting fees from Genentech, Pfizer, and Seattle Genetics. The other authors have nothing to disclose. Study concept and design were contributed by Yeung, Garrison, and Carlson. Yeung collected the data, which were interpreted by Yeung and Basu. The manuscript was written by Yeung, Suh, and Bansal and revised by Yeung. A portion of this research was presented at the Academy of Managed Care & Specialty Pharmacy Annual Meeting as a continuing education session entitled "Paying for Cures: How Can We Afford It?" on April 20, 2016, in San Francisco, California.

  9. Patent Pooling for Promoting Access to Antiretroviral Drugs (ARVs) - A Strategic Option for India.

    Science.gov (United States)

    Satyanarayana, Kanikaram; Srivastava, Sadhana

    2010-01-19

    The current HIV/AIDS scenario in India is quite grim with an estimated 2.4 million people living with HIV/AIDS (PLHA) in 2008, just behind South Africa and Nigeria. The anti-retroviral drugs (ARVs) remain the main stay of global HIV/AIDS treatment. Over 30 ARVs (single and FDCs) available under six categories viz., NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), Protease inhibitors, the new Fusion inhibitors, Entry inhibitors-CCR5 co-receptor antagonists and HIV integrase strand transfer inhibitors. The major originator companies for these ARVs are: Abbott, Boehringer Ingelheim (BI), Bristol-Myers Squibb (BMS), Gilead, GlaxoSmithKline (GSK), Merck, Pfizer, Roche, and Tibotec. Beginning with zidovidine in 1987, all the drugs are available in the developed countries. In India, about 30 ARVs are available as generics manufactured by Aurobindo, Hyderabad, Andhra Pradesh; Cipla Limited, Goa; Emcure Pharmaceuticals, Pune, Maharashtra; Hetero Drugs, Hyderabad, Andhra Pradesh; Macleods Pharmaceuticals, Daman; Matrix Laboratories, Nashik, Maharashtra; Ranbaxy, Sirmour, Himachal Pradesh; and Strides Arcolab, Bangalore, Karnataka. The National AIDS Control Organization (NACO) set up in 1992 by the Govt. of India provides free ARVs to HIV positive patients in India since 2004. The drugs available in India include both single drugs and FDCs covering both first line and second line ARVs. Even while there are claims of stabilization of the disease load, there is still huge gap of those who require ARVs as only about 150,000 PLHA receive the ARVs from the Govt. and other sources. Access to ARVs therefore is still a cause of serious concern ever since India became fully Trade Related Aspects of Intellectual Property Rights (TRIPS)-complaint in 2005. Therefore, the Indian pharmaceutical companies cannot make generics for those for drugs introduced post-2005 due to product patent regime. Other concerns include heat stable

  10. Analysis of treatment patterns and persistence on branded and generic medications in major depressive disorder using retrospective claims data

    Directory of Open Access Journals (Sweden)

    Solem CT

    2016-10-01

    Full Text Available Caitlyn T Solem,1 Ahmed Shelbaya,2,3 Yin Wan,1 Chinmay G Deshpande,1 Jose Alvir,2 Elizabeth Pappadopulos2 1Pharmerit International, Real World Evidence/Data Analytics, Bethesda, MD, 2Pfizer, Inc., Global Health Outcomes, New York, NY, 3Epidemiology Department of Mailman’s School of Public Health, Columbia University Mailman School of Public Health, New York, NY, USA Background: In major depressive disorder (MDD, treatment persistence is critical to optimize symptom remission, functional recovery, and health care costs. Desvenlafaxine tends to have fewer drug interactions and better tolerability than other MDD drugs; however, its use has not been assessed in the real world.Objective: The aim of the present study is to compare medication persistence and concomitant MDD drug use with branded desvenlafaxine (Pristiq® compared with antidepressant drug groups classified as 1 branded selective serotonin reuptake inhibitors (SSRIs; ie, escitalopram [Lexapro™] and selective serotonin–norepinephrine reuptake inhibitors (SNRIs; ie, venlafaxine [Effexor®], duloxetine [Cymbalta®] and 2 generic SSRIs/SNRIs (ie, escitalopram, citalopram, venlafaxine, fluvoxamine, fluoxetine, sertraline, paroxetine, and duloxetine.Patients and methods: MDD patients (ICD-9-CM codes 296.2, 296.3, with ≥2 prescription fills for study drugs and 12-month preindex continuous enrollment from the MarketScan Commercial Claims and Encounters Database (2009–2013, were included. Time-to-treatment discontinuation (prescription gap ≥45 days was assessed using the Kaplan–Meier curve and Cox model. Concomitant MDD drug use was compared.Results: Of the 273,514 patients included, 14,379 patients were initiated with branded desvenlafaxine, 50,937 patients with other branded SSRIs/SNRIs, and 208,198 patients with generic SSRIs/SNRIs. The number of weeks for treatment discontinuation for branded desvenlafaxine were longer (40.7 [95% CI: 39.3, 42.0] compared with other branded

  11. Cost-effectiveness of sunitinib as second-line treatment for gastrointestinal stromal tumor in the People’s Republic of China

    Directory of Open Access Journals (Sweden)

    Li J

    2017-01-01

    Full Text Available Jian Li,1 Hong Ye Ren,2 Juanjuan Zhang,2 Peng Dong,2 Yan Wang,3 Andrea L Stevens,3 Yi Han,3 Min Huang4 1Laboratory of Carcinogenesis and Translational Research for the Ministry of National Education, Department of GI Oncology, Peking University School of Oncology, Beijing Cancer Hospital & Institute, 2Pfizer Inc., Beijing, People’s Republic of China; 3WG Consulting, New York, NY, USA; 4School of Pharmacy, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China Objective: To evaluate the cost-effectiveness of sunitinib as a second-line treatment in patients with advanced gastrointestinal stromal tumors that no longer respond to imatinib 400 mg/d, compared with imatinib 600 mg/d, 800 mg/d, or best supportive care (BSC in the People’s Republic of China. Methods: This study was conducted from the government payer’s perspective with a time horizon of 5 years. Three health states were considered: progression-free survival, disease progression survival, and death, with a cycle length of 6 weeks. Probabilities of disease progression and death were estimated based on survival functions using exponential distribution and progression survival data in the clinical trials. Drug costs were based on drug retail prices and the patient assistance program in the People’s Republic of China, and adverse event management costs were based on published data and/or expert opinion. Uncertainties for parameters in the study were addressed through one-way deterministic and probabilistic sensitivity analysis. Results: When sunitinib was compared with imatinib 600 mg/d and BSC, the incremental cost-effectiveness ratio was RMB75,715 with RMB121,080 per quality-adjusted life-year (QALY gained. Sunitinib demonstrated lower costs and higher QALYs than imatinib 800 mg/d. In the probabilistic sensitivity analysis, the willingness-to-pay per QALY gained was set to be three times the per capita gross domestic product of the People’s Republic of

  12. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial.

    Science.gov (United States)

    Martin, Miguel; Holmes, Frankie A; Ejlertsen, Bent; Delaloge, Suzette; Moy, Beverly; Iwata, Hiroji; von Minckwitz, Gunter; Chia, Stephen K L; Mansi, Janine; Barrios, Carlos H; Gnant, Michael; Tomašević, Zorica; Denduluri, Neelima; Šeparović, Robert; Gokmen, Erhan; Bashford, Anna; Ruiz Borrego, Manuel; Kim, Sung-Bae; Jakobsen, Erik Hugger; Ciceniene, Audrone; Inoue, Kenichi; Overkamp, Friedrich; Heijns, Joan B; Armstrong, Anne C; Link, John S; Joy, Anil Abraham; Bryce, Richard; Wong, Alvin; Moran, Susan; Yao, Bin; Xu, Feng; Auerbach, Alan; Buyse, Marc; Chan, Arlene

    2017-12-01

    group had significantly fewer invasive disease-free survival events than those in the placebo group (116 vs 163 events; stratified hazard ratio 0·73, 95% CI 0·57-0·92, p=0·0083). The 5-year invasive disease-free survival was 90·2% (95% CI 88·3-91·8) in the neratinib group and 87·7% (85·7-89·4) in the placebo group. Without diarrhoea prophylaxis, the most common grade 3-4 adverse events in the neratinib group, compared with the placebo group, were diarrhoea (561 [40%] grade 3 and one [neratinib vs 23 [2%] grade 3 with placebo), vomiting (grade 3: 47 [3%] vs five [neratinib group and 85 (6%) women in the placebo group. No evidence of increased risk of long-term toxicity or long-term adverse consequences of neratinib-associated diarrhoea were identified with neratinib compared with placebo. At the 5-year follow-up, 1 year of extended adjuvant therapy with neratinib, administered after chemotherapy and trastuzumab, significantly reduced the proportion of clinically relevant breast cancer relapses-ie, those that might lead to death, such as distant and locoregional relapses outside the preserved breast-without increasing the risk of long-term toxicity. An analysis of overall survival is planned after 248 events. Wyeth, Pfizer, and Puma Biotechnology. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

    Science.gov (United States)

    Chan, Arlene; Delaloge, Suzette; Holmes, Frankie A; Moy, Beverly; Iwata, Hiroji; Harvey, Vernon J; Robert, Nicholas J; Silovski, Tajana; Gokmen, Erhan; von Minckwitz, Gunter; Ejlertsen, Bent; Chia, Stephen K L; Mansi, Janine; Barrios, Carlos H; Gnant, Michael; Buyse, Marc; Gore, Ira; Smith, John; Harker, Graydon; Masuda, Norikazu; Petrakova, Katarina; Zotano, Angel Guerrero; Iannotti, Nicholas; Rodriguez, Gladys; Tassone, Pierfrancesco; Wong, Alvin; Bryce, Richard; Ye, Yining; Yao, Bin; Martin, Miguel

    2016-03-01

    invasive disease-free survival events had occurred in patients in the neratinib group versus 109 events in those in the placebo group (stratified hazard ratio 0·67, 95% CI 0·50-0·91; p=0·0091). The 2-year invasive disease-free survival rate was 93·9% (95% CI 92·4-95·2) in the neratinib group and 91·6% (90·0-93·0) in the placebo group. The most common grade 3-4 adverse events in patients in the neratinib group were diarrhoea (grade 3, n=561 [40%] and grade 4, n=1 [neratinib and 93 (7%) patients given placebo, and decreases in left ventricular ejection fraction (≥grade 2) in 19 (1%) and 15 (1%) patients, respectively. We recorded serious adverse events in 103 (7%) patients in the neratinib group and 85 (6%) patients in the placebo group. Seven (neratinib group and three patients in the placebo group) unrelated to disease progression occurred after study drug discontinuation. The causes of death in the neratinib group were unknown (n=2), a second primary brain tumour (n=1), and acute myeloid leukaemia (n=1), and in the placebo group were a brain haemorrhage (n=1), myocardial infarction (n=1), and gastric cancer (n=1). None of the deaths were attributed to study treatment in either group. Neratinib for 12 months significantly improved 2-year invasive disease-free survival when given after chemotherapy and trastuzumab-based adjuvant therapy to women with HER2-positive breast cancer. Longer follow-up is needed to ensure that the improvement in breast cancer outcome is maintained. Wyeth, Pfizer, Puma Biotechnology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Pain severity and the economic burden of neuropathic pain in the United States: BEAT Neuropathic Pain Observational Study

    Directory of Open Access Journals (Sweden)

    Schaefer C

    2014-10-01

    Full Text Available Caroline Schaefer,1 Alesia Sadosky,2 Rachael Mann,3 Shoshana Daniel,4 Bruce Parsons,2 Michael Tuchman,5 Alan Anschel,6 Brett R Stacey,7 Srinivas Nalamachu,8 Edward Nieshoff9 1Covance Market Access Services Inc., Gaithersburg, MD, 2Pfizer, Inc., New York, NY, 3Covance Market Access Services Inc., San Diego, CA, 4Covance Market Access Services Inc., Conshohocken, PA, 5Palm Beach Neurological Center, Palm Beach Gardens, FL, 6Rehabilitation Institute of Chicago, Chicago, IL, 7Oregon Health and Science University, Portland, OR, 8International Clinical Research Institute, Overland Park, KS, 9Rehabilitation Institute of Michigan/Wayne State University, Detroit, MI, USABackground: As with many chronic conditions, patients with neuropathic pain (NeP are high consumers of health care resources. However, limited literature exists on the economic burden of NeP, including its impact on productivity. The aim of this study was to characterize health care resource utilization, productivity, and costs associated with NeP by pain severity level in US adults.Methods: Subjects (n=624 with painful diabetic peripheral neuropathy, human immunodeficiency virus-related peripheral NeP, post-trauma/post-surgical NeP, spinal cord injury with NeP, chronic low back pain with NeP, and small fiber neuropathy were recruited during routine office visits to US community-based general practitioners and specialists. Clinicians captured clinical characteristics, NeP-related medications, and health care resource utilization based on 6-month retrospective medical chart review. Subjects completed questionnaires on demographics, pain/symptoms, costs, and productivity. Brief Pain Inventory pain severity scores were used to classify subjects by mild, moderate, or severe pain. Annualized NeP-related costs (adjusted for covariates were estimated, and differences across pain severity groups were evaluated.Results: In total, 624 subjects were recruited (mean age 55.5±13.7 years; 55.4% male

  15. Indian vaccine innovation: the case of Shantha Biotechnics

    Directory of Open Access Journals (Sweden)

    Heys Jennifer

    2011-04-01

    Full Text Available Abstract Background Although the World Health Organization had recommended that every child be vaccinated for Hepatitis B by the early 1980s, large multinational pharmaceutical companies held monopolies on the recombinant Hepatitis B vaccine. At a price as high as USD$23 a dose, most Indians families could not afford vaccination. Shantha Biotechnics, a pioneering Indian biotechnology company founded in 1993, saw an unmet need domestically, and developed novel processes for manufacturing Hepatitis B vaccine to reduce prices to less than $1/dose. Further expansion enabled low-cost mass vaccination globally through organizations such as UNICEF. In 2009, Shantha sold over 120 million doses of vaccines. The company was recently acquired by Sanofi-Aventis at a valuation of USD$784 million. Methods The case study and grounded research method was used to illustrate how the globalization of healthcare R&D is enabling private sector companies such as Shantha to address access to essential medicines. Sources including interviews, literature analysis, and on-site observations were combined to conduct a robust examination of Shantha's evolution as a major provider of vaccines for global health indications. Results Shantha's ability to become a significant global vaccine manufacturer and achieve international valuation and market success appears to have been made possible by focusing first on the local health needs of India. How Shantha achieved this balance can be understood in terms of a framework of four guiding principles. First, Shantha identified a therapeutic area (Hepatitis B in which cost efficiencies could be achieved for reaching the poor. Second, Shantha persistently sought investments and partnerships from non-traditional and international sources including the Foreign Ministry of Oman and Pfizer. Third, Shantha focused on innovation and quality - investing in innovation from the outset yielded the crucial process innovation that allowed Shantha

  16. Indian vaccine innovation: the case of Shantha Biotechnics.

    Science.gov (United States)

    Chakma, Justin; Masum, Hassan; Perampaladas, Kumar; Heys, Jennifer; Singer, Peter A

    2011-04-20

    Although the World Health Organization had recommended that every child be vaccinated for Hepatitis B by the early 1980s, large multinational pharmaceutical companies held monopolies on the recombinant Hepatitis B vaccine. At a price as high as USD$23 a dose, most Indians families could not afford vaccination. Shantha Biotechnics, a pioneering Indian biotechnology company founded in 1993, saw an unmet need domestically, and developed novel processes for manufacturing Hepatitis B vaccine to reduce prices to less than $1/dose. Further expansion enabled low-cost mass vaccination globally through organizations such as UNICEF. In 2009, Shantha sold over 120 million doses of vaccines. The company was recently acquired by Sanofi-Aventis at a valuation of USD$784 million. The case study and grounded research method was used to illustrate how the globalization of healthcare R&D is enabling private sector companies such as Shantha to address access to essential medicines. Sources including interviews, literature analysis, and on-site observations were combined to conduct a robust examination of Shantha's evolution as a major provider of vaccines for global health indications. Shantha's ability to become a significant global vaccine manufacturer and achieve international valuation and market success appears to have been made possible by focusing first on the local health needs of India. How Shantha achieved this balance can be understood in terms of a framework of four guiding principles. First, Shantha identified a therapeutic area (Hepatitis B) in which cost efficiencies could be achieved for reaching the poor. Second, Shantha persistently sought investments and partnerships from non-traditional and international sources including the Foreign Ministry of Oman and Pfizer. Third, Shantha focused on innovation and quality - investing in innovation from the outset yielded the crucial process innovation that allowed Shantha to make an affordable vaccine. Fourth, Shantha

  17. Axitinib with or without dose titration for first-line metastatic renal-cell carcinoma: a randomised double-blind phase 2 trial

    Science.gov (United States)

    Rini, Brian I; Melichar, Bohuslav; Ueda, Takeshi; GrÜnwald, Viktor; Fishman, Mayer N; Arranz, José A; Bair, Angel H; Pithavala, Yazdi K; Andrews, Glen I; Pavlov, Dmitri; Kim, Sinil; Jonasch, Eric

    2014-01-01

    -randomised patients achieved an objective response. Common grade 3 or worse, all-causality adverse events in treated patients were hypertension (ten [18%] of 56 in the axitinib titration group vs five [9%] of 56 in the placebo titration group vs 45 [49%] of 91 in the non-randomised group), diarrhoea (seven [13%] vs two [4%] vs eight [9%]), and decreased weight (four [7%] vs three [5%] vs six [7%]). One or more all-causality serious adverse events were reported in 15 (27%) patients in the axitinib titration group, 13 (23%) patients in the placebo titration group, and 35 (38%) non-randomised patients. The most common serious adverse events in all 213 patients were disease progression and dehydration (eight each [4%]), and diarrhoea, vomiting, pneumonia, and decreased appetite (four each [2%]). Interpretation The greater proportion of patients in the axitinib titration group achieving an objective response supports the concept of individual axitinib dose titration in selected patients with metastatic renal-cell carcinoma. Axitinib shows clinical activity with a manageable safety profile in treatment-naive patients with this disease. Funding Pfizer Inc. PMID:24140184

  18. Collagenase injections for the treatment of single cords in cases of Dupuytren’s contracture – a prospective intervention study of long-term experience with Xiapex

    Directory of Open Access Journals (Sweden)

    Fischer, Lisa Maria

    2017-04-01

    Full Text Available Introduction: The gold standard in the treatment of Dupuytren’s contracture is surgical therapy. Alternatives are percutaneous needle fasciotomy and radiation in exceptional cases. Injection treatments with Xiapex (Pfizer are a new therapy option. This collagenase, extracted from clostridium histolyticum, is used to break down the affected tissue cords. The objective of this study is to examine the effect and long-term success of treatment with Xiapex.Methods: In this study, Xiapex treatment was conducted on a sample group of 19 patients with Dupuytren’s contracture. The injection was placed either on the cord at the level of the metacarpophalangeal (MCP joint (n=17 or of the proximal interphalangeal (PIP joint (n=7. Break-up of the cord occurred 24 hours after the injection. The neutral zero method was used to assess the extent of movement. The Michigan Hand Outcomes Questionnaire (MHQ was selected for evaluation of the general hand function in 16 patients. The WHO-5 and the EQ-5D VAS Score were used as a measure of the patients’ satisfaction and their state of health. All values were collected both pre-injection as well as 1 year post-injection.Results: Out of 19 patients in our sample group, 16 patients (≈84% benefitted in terms of improvement in mobility. Overall, the range of movement increased by Ø 26° in the affected finger. A separate assessment demonstrated that:The range of movement increased by 77% in the MCP joint. The extent of movement pre-injection was Ø (0-28-78 and post-injection it was Ø (0-9-81 with an improvement of Ø 22°. In the PIP joint, only slight improvement was observed (Ø pre (0-27-93; post (0-24-95.The MHQ increased from Ø 76% (R: 32–97% to 81% (R: 39–100%.The painfulness decreased from Ø 19% (R: 0–55% to Ø11% (R: 0–55%, corresponding to Ø 43%. Satisfaction increased in 72% of patients by Ø 21%.According to WHO-5, patient satisfaction pre-injection was Ø 20 (R: 11–25, and 1 year after

  19. Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial.

    Science.gov (United States)

    Gulley, James L; Rajan, Arun; Spigel, David R; Iannotti, Nicholas; Chandler, Jason; Wong, Deborah J L; Leach, Joseph; Edenfield, W Jeff; Wang, Ding; Grote, Hans Juergen; Heydebreck, Anja von; Chin, Kevin; Cuillerot, Jean-Marie; Kelly, Karen

    2017-05-01

    increased lipase level (three [2%]). 16 (9%) of 184 patients had a serious adverse event related to treatment with avelumab, with infusion-related reaction (in four [2%] patients) and dyspnoea (in two [1%]) occurring in more than one patient. Serious adverse events irrespective of cause occurred in 80 (44%) of 184 patients. Those occurring in more than five patients (≥3%) were dyspnoea (ten patients [5%]), pneumonia (nine [5%]), and chronic obstructive pulmonary disease (six [3%]). Immune-related treatment-related events occurred in 22 patients (12%). Of 184 patients, 22 (12% [95% CI 8-18]) achieved a confirmed objective response, including one complete response and 21 partial responses. 70 (38%) had stable disease. Overall, 92 (50%) of 184 patients achieved disease control (they had a confirmed response or stable disease as their best overall response). One patient was initially thought to have died from grade 5 radiation pneumonitis during the study; however, this adverse event was subsequently regraded to grade 3 and the death was attributed to disease progression. Avelumab showed an acceptable safety profile and antitumour activity in patients with progressive or treatment-resistant NSCLC, providing a rationale for further studies of avelumab in this disease setting. Merck KGaA and Pfizer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial.

    Science.gov (United States)

    Patel, Manish R; Ellerton, John; Infante, Jeffrey R; Agrawal, Manish; Gordon, Michael; Aljumaily, Raid; Britten, Carolyn D; Dirix, Luc; Lee, Keun-Wook; Taylor, Mathew; Schöffski, Patrick; Wang, Ding; Ravaud, Alain; Gelb, Arnold B; Xiong, Junyuan; Rosen, Galit; Gulley, James L; Apolo, Andrea B

    2018-01-01

    , 2014, and March 15, 2016, 329 patients with advanced metastatic urothelial carcinoma were screened for enrolment into this study; 249 patients were eligible and received treatment with avelumab for a median of 12 weeks (IQR 6·0-19·7) and followed up for a median of 9·9 months (4·3-12·1). Safety and antitumour activity were evaluated at data cutoff on June 9, 2016. In 161 post-platinum patients with at least 6 months of follow-up, a best overall response of complete or partial response was recorded in 27 patients (17%; 95% CI 11-24), including nine (6%) complete responses and 18 (11%) partial responses. The most frequent treatment-related adverse events (any grade in ≥10% patients) were infusion-related reaction (73 [29%]; all grade 1-2) and fatigue (40 [16%]). Grade 3 or worse treatment-related adverse events occurred in 21 (8%) of 249 patients, the most common of which were fatigue (four [2%]), and asthenia, elevated lipase, hypophosphataemia, and pneumonitis in two (1%) patients each. 19 (8%) of 249 patients had a serious adverse event related to treatment with avelumab, and one treatment-related death occurred (pneumonitis). Avelumab showed antitumour activity in the treatment of patients with platinum-refractory metastatic urothelial carcinoma; a manageable safety profile was reported in all avelumab-treated patients. These data provide the rationale for therapeutic use of avelumab in metastatic urothelial carcinoma and it has received accelerated US FDA approval in this setting on this basis. Merck KGaA, and Pfizer Inc. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN Renal 100): an open-label, dose-finding and dose-expansion, phase 1b trial.

    Science.gov (United States)

    Choueiri, Toni K; Larkin, James; Oya, Mototsugu; Thistlethwaite, Fiona; Martignoni, Marcella; Nathan, Paul; Powles, Thomas; McDermott, David; Robbins, Paul B; Chism, David D; Cho, Daniel; Atkins, Michael B; Gordon, Michael S; Gupta, Sumati; Uemura, Hirotsugu; Tomita, Yoshihiko; Compagnoni, Anna; Fowst, Camilla; di Pietro, Alessandra; Rini, Brian I

    2018-04-01

    dose-expansion phase of the study. One dose-limiting toxicity of grade 3 proteinuria due to axitinib was reported among the six patients treated during the dose-finding phase. At the cutoff date (April 13, 2017), six (100%, 95% CI 54-100) of six patients in the dose-finding phase and 26 (53%, 38-68) of 49 patients in the dose-expansion phase had confirmed objective responses (32 [58%, 44-71] of all 55 patients). 32 (58%) of 55 patients had grade 3 or worse treatment-related adverse events, the most frequent being hypertension in 16 (29%) patients and increased concentrations of alanine aminotransferase, amylase, and lipase, and palmar-plantar erythrodysaesthesia syndrome in four (7%) patients each. Six (11%) of 55 patients died before data cutoff, five (9%) due to disease progression and one (2%) due to treatment-related autoimmune myocarditis. At the end of the dose-finding phase, the maximum tolerated dose established for the combination was avelumab 10 mg/kg every 2 weeks and axitinib 5 mg twice daily. The safety profile of the combination avelumab plus axitinib in treatment-naive patients with advanced renal-cell carcinoma seemed to be manageable and consistent with that of each drug alone, and the preliminary data on antitumour activity are encouraging. A phase 3 trial is assessing avelumab and axitinib compared with sunitinib monotherapy. Pfizer and Merck. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Efficacy and safety of prostaglandin analogues in patients with predominantly primary open-angle glaucoma or ocular hypertension: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Oghenowede Eyawo

    2009-07-01

    Full Text Available Oghenowede Eyawo1, Jean Nachega2,3, Pierre Lefebvre4, David Meyer5, Beth Rachlis6, Chia-Wen Lee7, Steven Kelly7, Edward Mills81Faculty of Health Sciences, Simon Fraser University, Vancouver, Canada; 2Division of Clinical Pharmacology and Medicine, University of Cape Town, Cape Town, South Africa; 3Johns Hopkins Bloomberg School of Public Health, Baltimore, USA; 4Department of Ophthalmology, Moorfields Eye Hospital, London, United Kingdom; 5Department of Ophthalmology, Stellenbosch University, Cape Town, South Africa; 6Department of Public Health, University of Toronto, Toronto, Canada; 7Outcome Research and Evidence Based Medicine, Pfizer Ltd UK. Tadworth, UK; 8Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, CanadaBackground: First-line therapy for primary open-angle glaucoma and ocular hypertension generally involves prostaglandin analogue therapy. The relative efficacy of differing prostaglandin therapy is disputed.Methods: A meta-analysis was conducted of head-to-head randomized trials of prostaglandin therapies. We included randomized trials assessing head-to-head evaluations of prostaglandin analogues travoprost, latanoprost and bimatoprost in patients with predominantly primary open-angle glaucoma or ocular hypertension. Findings were interpreted in light of equivalence margins.Results: Our search identified 16 eligible trials, of which 15 were included in the meta-analysis. Trials were, in general, poorly reported. We pooled 9 trials assessing IOP-lowering effects of travoprost vs latanoprost (total n = 1098, weighted mean difference [WMD], –0.24 mmHg, 95% CI, –0.87 to 0.38, P = 0.45, I2 = 56%, 95% CI, 0 to 0.77, heterogeneity P = 0.01. Eight trials assessed travoprost vs bimatoprost (total n = 714, WMD, 0.88 mmHg, 95% CI, 0.13 to 1.63, P = 0.02, I2 = 56%, 95% CI, 0% to 78%, heterogeneity P = 0.02. And 8 trials assessed latanoprost vs bimatoprost (total n = 943, WMD, 0.73 mmHg, 95% CI, 0.10 to 1

  3. AMCP Partnership Forum: FDAMA Section 114-Improving the Exchange of Health Care Economic Data.

    Science.gov (United States)

    2016-07-01

    & Co., National Pharmaceutical Council, Pharmaceutical Research and Manufacturers of America, Precision for Value, Pfizer, Takeda Pharmaceuticals, U.S.A., and Xcenda. All sponsors participated in the forum and participated in revising and approving the manuscript.

  4. Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: a non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial.

    Science.gov (United States)

    Atkins, Michael B; Plimack, Elizabeth R; Puzanov, Igor; Fishman, Mayer N; McDermott, David F; Cho, Daniel C; Vaishampayan, Ulka; George, Saby; Olencki, Thomas E; Tarazi, Jamal C; Rosbrook, Brad; Fernandez, Kathrine C; Lechuga, Mariajose; Choueiri, Toni K

    2018-03-01

    observed. Three dose-limiting toxicities were reported in the 11 patients treated during the 6-week observation period (dose-finding phase): one patient had a transient ischaemic attack and two patients were only able to complete less than 75% of the planned axitinib dose because of treatment-related toxicity. At the data cutoff date (March 31, 2017), 25 (48%) patients were still receiving study treatment. Grade 3 or worse treatment-related adverse events occurred in 34 (65%) patients; the most common included hypertension (n=12 [23%]), diarrhoea (n=5 [10%]), fatigue (n=5 [10%]), and increased alanine aminotransferase concentration (n=4 [8%]). The most common potentially immune-related adverse events (probably related to pembrolizumab) included diarrhoea (n=15 [29%]), increased alanine aminotransferase concentration (n=9 [17%]) or aspartate aminotransferase concentration (n=7 [13%]), hypothyroidism (n=7 [13%]), and fatigue (n=6 [12%]). 28 (54%) patients had treatment-related serious adverse events. At data cutoff, 38 (73%; 95% CI 59·0-84·4) patients achieved an objective response (complete or partial response). The treatment combination of axitinib plus pembrolizumab is tolerable and shows promising antitumour activity in patients with treatment-naive advanced renal cell carcinoma. Whether or not the combination works better than a sequence of VEGF pathway inhibition followed by an anti-PD-1 therapy awaits the completion of a phase 3 trial comparing axitinib plus pembrolizumab with sunitinib monotherapy (NCT02853331). Pfizer Inc. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Dr. Alberto Albornoz Plata

    Directory of Open Access Journals (Sweden)

    Zoilo Cuellar Montoya

    2009-01-01

    Full Text Available

    A pesar de la diferencia de edades que nos separaba generacionalmente existió, entre Alberto y quien esto escribe, una estrecha amistad, que sobrepasa, en el momento de su dolorosa desaparición, los cuarenta y siete años, pues se originó, al impulso de vínculos familiares con su primera esposa, Doña Cecilia Ucrós de Albornoz, en la época en que yo culminaba mi carrera de medicina, cuando se inició la gran amistad que nos ha unido, desde entonces, con su hija Margarita y algo después, cuando él ocupaba el cargo de Director Científico de PFIZER de Colombia.

    En el año de 1963, en virtud de mi interés por realizar, como trabajo de tesis, un estudio de investigación sobre hepatitis experimental en perros, estudio respaldado por dicho laboratorio, debí ponerme en contacto con Alberto, en varias oportunidades, con el fin de planear el proyecto, de común acuerdo.

    Desafortunadamente, el trabajo se frustró y pasaron varios años antes de que nos volviéramos a ver. Fue con ocasión de la muerte de Cecilia que nos vimos de nuevo y, algo más tarde, en la Academia Nacional de Medicina, a partir de 1980, cuando volvimos a compartir intereses y a reafianzar nuestra amistad. Siempre admiré la distinción de Alberto, su impecable pulcritud, tanto en el vestir como, fundamentalmente, en su actuar, en sus maneras y en su trato, clásico de un caballero a carta cabal, como lo era él, porte que se mantenía constante, en su ejercicio profesional igual que en su relación con los colegas, con los pacientes, con sus discípulos, con los amigos y con los íntimos. Cómo admiré su ciencia, su alto profesionalismo, que le imprimían carácter a todas sus actuaciones en el ejercicio médico y que habían modelado, durante los años de generosa dedicación a sus pacientes, esa personalidad de quien no debió hacer el menor esfuerzo para inspirar confianza, en todos los que nos acercamos a él, bien se tratara de disc

  6. The Problem with the Low-Tax Backlash: Rethinking Corporate Tax Policies to Adjust for Uneven Reputational Risks

    Directory of Open Access Journals (Sweden)

    Jack M. Mintz

    2015-05-01

    Full Text Available When a major corporation is found to be paying little or no taxes, public backlash and media furor over the issue may ensue. Some governments may well be just fine with it, while others like U.S. may take steps to ensure companies pay more tax. Sometimes, companies being in a non-taxpaying position properly reflects appropriate tax policy. That explanation, however, does not sell lattés, which is why in 2012, after the British public grew outraged over the discovery that Starbucks was paying no corporate taxes in the U.K., the coffee retailer actually volunteered to just write a cheque to the government. The reputational damage to Starbucks’ brand, the company calculated, was not worth the money it was saving in avoiding taxes, even if it was doing so perfectly legally. The fear of this kind of reputational damage can foil the very taxation policies that governments design specifically as a means to tax corporations fairly, efficiently and competitively. It may be good tax policy to allow corporations various deductions, or the ability to carry forward or carry back losses, but it can be politically vexatious. U.S. President Barack Obama demonstrated that explicitly when he suggested certain American companies using so-called tax inversions to relocate their headquarters to low-tax jurisdictions, were failing in their “economic patriotism.” Yet more multinationals than ever are legally and quite appropriately using tax strategies to minimize their taxes in various jurisdictions to the point where they are paying little to no corporate tax. For some corporations, the risk of public backlash is greater than it is for others: Starbucks and Facebook, being consumer-facing companies with a great deal of brand goodwill, have a lot more at risk than do Pfizer and Oracle. This risk makes the playing field for taxation less level, jeopardizing the fundamental tax principle of horizontal equity — that those of similar means should pay similar

  7. Proceedings of Synthetic Biology: Engineering, Evolution and Design (SEED) Conference 2015

    Energy Technology Data Exchange (ETDEWEB)

    Silver, Pamela [Harvard Univ., Cambridge, MA (United States); SEED 2015 Conference Chair; Flach, Evan [American Institute of Chemical Engineers; SEED 2015 Conference Organizer

    2016-10-27

    Synthetic Biology is an emerging discipline that seeks to accelerate the process of engineering biology. As such, the tools are broadly applicable to application areas, including chemicals and biofuels, materials, medicine and agriculture. A characteristic of the field is to look holistically at cellular design, from sensing and genetic circuitry to the manipulation of cellular processes and actuators, to controlling metabolism, to programming multicellular behaviors. Further, the types of cells that are manipulated are broad, from in vitro systems to microbes and fungi to mammalian and plant cells and living animals. Many of the projects in synthetic biology seek to move biochemical functions across organisms. The field is highly interdisciplinary with faculty and students spread across departments that focus on engineering (biological, chemical, electrical, mechanical, civil, computer science) and basic science (biology and systems biology, chemistry, physics). While there have been many one-off workshops and meeting on synthetic biology, the 2014 Synthetic Biology: Engineering, Evolution and Design (SEED) was the first of an annual conference series that serves as a reliable place to pull together the involved disciplines in order to organize and exchange advances in the science and technology in the field. Further, the SEED conferences have a strong focus on industry, with many companies represented and actively participating. A number of these companies have started major efforts in synthetic biology including large companies (e.g., Pfizer, Novartis, Dow, Dupont, BP, Total), smaller companies have recently gone public (e.g., Amyris, Gevo, Intrexon), and many start-ups (e.g., Teslagen, Refactored Materials, Pivot, Genomatica). There are a number of loosely affiliated Synthetic Biology Centers, including ones at MIT, Boston University, UCSD, UCSF, UC-Berkeley, Imperial College, Oxford, and ETH. SEED 2015 will serve as the primary meeting at which international

  8. The innovative use of a large-scale industry biomedical consortium to research the genetic basis of drug induced serious adverse events.

    Science.gov (United States)

    Holden, Arthur L

    2007-01-01

    communities about issues related to severe adverse drug reactions and about issues related to the Consortium's research.The SAEC was launched in late September of 2007 with the scientific, technical and financial support of eight founding industrial research-funding members (i.e. Abbott, GSK, J & J, Novartis, Pfizer, Roche, Sanofi-Aventis and Wyeth). Additional members are being added as the consortium executes its phase one research program and develops its future plans.The Consortium's will focus initially on two research projects. It will attempt to identify DNA variants associated with drug-induced liver-disease and serious skin rashes [e.g. Stevens-Johnson syndrome ('SJS') and toxic epidermal necrolysis ('TEN')]. These two projects, while important in their own right, will also allow the SAEC to generate initial results in a reasonable time frame (owing to the availability of established case-control DNA sample collections) and build its core operations. Simultaneous with the Phase 1 research activities, the SAEC will plan follow on, hypothesis driven studies (post whole genome association studies) for DILI and SJS and explore the feasibility of whole genome research on additional SAEs. Our long term goal is to discover and validate genetic markers predictive of the major drug induced, rare SAEs and make these available at no cost at the same time, unencumbered by any intellectual property constraints, to all researchers and developers of clinical diagnostics. � 2007 Published by Elsevier Ltd.

  9. Assessment of dexrazoxane as a cardioprotectant in doxorubicin-treated children with high-risk acute lymphoblastic leukaemia: long-term follow-up of a prospective, randomised, multicentre trial.

    Science.gov (United States)

    Lipshultz, Steven E; Scully, Rebecca E; Lipsitz, Stuart R; Sallan, Stephen E; Silverman, Lewis B; Miller, Tracie L; Barry, Elly V; Asselin, Barbara L; Athale, Uma; Clavell, Luis A; Larsen, Eric; Moghrabi, Albert; Samson, Yvan; Michon, Bruno; Schorin, Marshall A; Cohen, Harvey J; Neuberg, Donna S; Orav, E John; Colan, Steven D

    2010-10-01

    between groups: 0·47, 0·46-0·48) and thickness-to-dimension ratio (0·66, 0·64-0·68) were the only statistically significant characteristics at 5 years. Subgroup analysis showed dexrazoxane protection (p=0·04) for left ventricular fractional shortening at 5 years in girls (1·17, 0·24-2·11), but not in boys (-0·10, -0·87 to 0·68). Similarly, subgroup analysis showed dexrazoxane protection (p=0·046) for the left ventricular thickness-to-dimension ratio at 5 years in girls (1·15, 0·44-1·85), but not in boys (0·19, -0·42 to 0·81). With a median follow-up for recurrence and death of 8·7 years (range 1·3-12·1), event-free survival was 77% (95% CI 67-84) for children in the doxorubicin-alone group, and 76% (67-84) for children in the doxorubicin plus dexrazoxane group (p=0·99). Dexrazoxane provides long-term cardioprotection without compromising oncological efficacy in doxorubicin-treated children with high-risk ALL. Dexrazoxane exerts greater long-term cardioprotective effects in girls than in boys. US National Institutes of Health, Children's Cardiomyopathy Foundation, University of Miami Women's Cancer Association, Lance Armstrong Foundation, Roche Diagnostics, Pfizer, and Novartis. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. Effects of adjuvant exemestane versus anastrozole on bone mineral density for women with early breast cancer (MA.27B): a companion analysis of a randomised controlled trial.

    Science.gov (United States)

    Goss, Paul E; Hershman, Dawn L; Cheung, Angela M; Ingle, James N; Khosla, Sundeep; Stearns, Vered; Chalchal, Haji; Rowland, Kendrith; Muss, Hyman B; Linden, Hannah M; Scher, Judite; Pritchard, Kathleen I; Elliott, Catherine R; Badovinac-Crnjevic, Tanja; St Louis, Jessica; Chapman, Judith-Anne W; Shepherd, Lois E

    2014-04-01

    =0·08). Respective mean loss in the hip was -1·93% (95% CI -2·93 to -0·93) versus -2·71% (95% CI -4·32 to -1·11; p=0·10). Likewise for those who started with T-scores of less than -2·0, mean change of spine bone mineral density at 2 years did not differ significantly between the exemestane and anastrozole treatment groups (2·11%, 95% CI -0·84 to 5·06 vs 3·72%, 95% CI 1·54 to 5·89; p=0·26), nor did hip bone mineral density (2·09%, 95% CI -1·45 to 5·63 vs 0·0%, 95% CI -3·67 to 3·66; p=0·28). Patients with baseline T-score of -2·0 or more taking exemestane had two fragility fractures and two other fractures, those taking anastrozole had three fragility fractures and five other fractures. For patients who had baseline T-scores of less than -2·0 taking exemestane, one had a fragility fracture and four had other fractures, whereas those taking anastrozole had five fragility fractures and one other fracture. Our results demonstrate that adjuvant treatment with aromatase inhibitors can be considered for breast cancer patients who have T-scores less than -2·0. Canadian Cancer Society Research Institute, Pfizer, Canadian Institutes of Health Research. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Use of low-density lipoprotein cholesterol gene score to distinguish patients with polygenic and monogenic familial hypercholesterolaemia: a case-control study.

    Science.gov (United States)

    Talmud, Philippa J; Shah, Sonia; Whittall, Ros; Futema, Marta; Howard, Philip; Cooper, Jackie A; Harrison, Seamus C; Li, Kawah; Drenos, Fotios; Karpe, Frederik; Neil, H Andrew W; Descamps, Olivier S; Langenberg, Claudia; Lench, Nicholas; Kivimaki, Mika; Whittaker, John; Hingorani, Aroon D; Kumari, Meena; Humphries, Steve E

    2013-04-13

    familial hypercholesterolaemia without a known mutation, their raised LDL-C concentrations might have a polygenic cause, which could compromise the efficiency of cascade testing. In patients with a detected mutation, a substantial polygenic contribution might add to the variable penetrance of the disease. British Heart Foundation, Pfizer, AstraZeneca, Schering-Plough, National Institute for Health Research, Medical Research Council, Health and Safety Executive, Department of Health, National Heart Lung and Blood Institute, National Institute on Aging, Agency for Health Care Policy Research, John D and Catherine T MacArthur Foundation Research Networks on Successful Midlife Development and Socio-economic Status and Health, Unilever, and Departments of Health and Trade and Industry. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Alpha-2 agonists for sedation of mechanically ventilated adults in intensive care units: a systematic review.

    Science.gov (United States)

    Cruickshank, Moira; Henderson, Lorna; MacLennan, Graeme; Fraser, Cynthia; Campbell, Marion; Blackwood, Bronagh; Gordon, Anthony; Brazzelli, Miriam

    2016-03-01

    Care of critically ill patients in intensive care units (ICUs) often requires potentially invasive or uncomfortable procedures, such as mechanical ventilation (MV). Sedation can alleviate pain and discomfort, provide protection from stressful or harmful events, prevent anxiety and promote sleep. Various sedative agents are available for use in ICUs. In the UK, the most commonly used sedatives are propofol (Diprivan(®), AstraZeneca), benzodiazepines [e.g. midazolam (Hypnovel(®), Roche) and lorazepam (Ativan(®), Pfizer)] and alpha-2 adrenergic receptor agonists [e.g. dexmedetomidine (Dexdor(®), Orion Corporation) and clonidine (Catapres(®), Boehringer Ingelheim)]. Sedative agents vary in onset/duration of effects and in their side effects. The pattern of sedation of alpha-2 agonists is quite different from that of other sedatives in that patients can be aroused readily and their cognitive performance on psychometric tests is usually preserved. Moreover, respiratory depression is less frequent after alpha-2 agonists than after other sedative agents. To conduct a systematic review to evaluate the comparative effects of alpha-2 agonists (dexmedetomidine and clonidine) and propofol or benzodiazepines (midazolam and lorazepam) in mechanically ventilated adults admitted to ICUs. We searched major electronic databases (e.g. MEDLINE without revisions, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE and Cochrane Central Register of Controlled Trials) from 1999 to 2014. Evidence was considered from randomised controlled trials (RCTs) comparing dexmedetomidine with clonidine or dexmedetomidine or clonidine with propofol or benzodiazepines such as midazolam, lorazepam and diazepam (Diazemuls(®), Actavis UK Limited). Primary outcomes included mortality, duration of MV, length of ICU stay and adverse events. One reviewer extracted data and assessed the risk of bias of included trials. A second reviewer cross-checked all the data extracted. Random-effects meta

  13. Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study.

    Science.gov (United States)

    O'Donnell, Martin J; Chin, Siu Lim; Rangarajan, Sumathy; Xavier, Denis; Liu, Lisheng; Zhang, Hongye; Rao-Melacini, Purnima; Zhang, Xiaohe; Pais, Prem; Agapay, Steven; Lopez-Jaramillo, Patricio; Damasceno, Albertino; Langhorne, Peter; McQueen, Matthew J; Rosengren, Annika; Dehghan, Mahshid; Hankey, Graeme J; Dans, Antonio L; Elsayed, Ahmed; Avezum, Alvaro; Mondo, Charles; Diener, Hans-Christoph; Ryglewicz, Danuta; Czlonkowska, Anna; Pogosova, Nana; Weimar, Christian; Iqbal, Romaina; Diaz, Rafael; Yusoff, Khalid; Yusufali, Afzalhussein; Oguz, Aytekin; Wang, Xingyu; Penaherrera, Ernesto; Lanas, Fernando; Ogah, Okechukwu S; Ogunniyi, Adesola; Iversen, Helle K; Malaga, German; Rumboldt, Zvonko; Oveisgharan, Shahram; Al Hussain, Fawaz; Magazi, Daliwonga; Nilanont, Yongchai; Ferguson, John; Pare, Guillaume; Yusuf, Salim

    2016-08-20

    -2·67 for high or heavy episodic intake vs never or former drinker; 5·8%, 3·4-9·7 for current alcohol drinker vs never or former drinker), and diabetes mellitus (1·16, 1·05-1·30; 3·9%, 1·9-7·6) were associated with all stroke. Collectively, these risk factors accounted for 90·7% of the PAR for all stroke worldwide (91·5% for ischaemic stroke, 87·1% for intracerebral haemorrhage), and were consistent across regions (ranging from 82·7% in Africa to 97·4% in southeast Asia), sex (90·6% in men and in women), and age groups (92·2% in patients aged ≤55 years, 90·0% in patients aged >55 years). We observed regional variations in the importance of individual risk factors, which were related to variations in the magnitude of ORs (rather than direction, which we observed for diet) and differences in prevalence of risk factors among regions. Hypertension was more associated with intracerebral haemorrhage than with ischaemic stroke, whereas current smoking, diabetes, apolipoproteins, and cardiac causes were more associated with ischaemic stroke (pworld, among ethnic groups, in men and women, and in all ages. However, we found important regional variations in the relative importance of most individual risk factors for stroke, which could contribute to worldwide variations in frequency and case-mix of stroke. Our findings support developing both global and region-specific programmes to prevent stroke. Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland (Sweden), AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Effect of ADRB2 polymorphisms on the efficacy of salmeterol and tiotropium in preventing COPD exacerbations: a prespecified substudy of the POET-COPD trial.

    Science.gov (United States)

    Rabe, Klaus F; Fabbri, Leonardo M; Israel, Elliot; Kögler, Harald; Riemann, Kathrin; Schmidt, Hendrik; Glaab, Thomas; Vogelmeier, Claus F

    2014-01-01

    exacerbation risk compared with patients with Arg16Gly (p=0·0130) and Gly16Gly (p=0·0018) genotypes (proportion of patients with at least one exacerbation was 32·3% in Arg16Arg, 39·8% in Arg16Gly, and 42·1% in Gly16Gly). By contrast, exacerbation risk was not modified by polymorphisms at aminoacid 16 in the tiotropium group. The effect of the Arg16Gly polymorphism on treatment response to salmeterol was dependent on the use of inhaled corticosteroids (ICS). In patients untreated with ICS at baseline, Arg16Gly and Arg16Arg genotypes were associated with significantly prolonged time to first exacerbation compared with Gly16Gly (vs Arg16Gly p=0·0164; Arg16Arg p=0·0316; proportion of patients with at least one exacerbation was 28·3% in Arg16Arg, 31·6% in Arg16Gly, and 39·2% in Gly16Gly), whereas in patients on ICS at baseline, only the Arg16Arg genotype was associated with significantly prolonged time to first exacerbation compared with Gly16Gly (p=0·0198; not Arg16Gly p=0·64; proportion of patients with at least one exacerbation was 35·9% in Arg16Arg, 46·7% in Arg16Gly, and 44·8% in Gly16Gly). The respiratory disorders, in particular worsening of COPD, were the most common serious adverse events. Patients with the Arg16Arg genotype had better exacerbation outcomes in response to salmeterol than Gly16Gly and Arg16Gly genotypes, suggesting a potential differential Arg16Gly genotype effect on treatment response to longacting β-agonists (LABAs). However, the use of ADRB2 polymorphisms for predicting LABA treatment response is still limited and further prospective validation will be needed to advance the mechanistic understanding of β-adrenergic polymorphisms and their association with clinical features of COPD. Boehringer Ingelheim and Pfizer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial.

    Science.gov (United States)

    Cristofanilli, Massimo; Turner, Nicholas C; Bondarenko, Igor; Ro, Jungsil; Im, Seock-Ah; Masuda, Norikazu; Colleoni, Marco; DeMichele, Angela; Loi, Sherene; Verma, Sunil; Iwata, Hiroji; Harbeck, Nadia; Zhang, Ke; Theall, Kathy Puyana; Jiang, Yuqiu; Bartlett, Cynthia Huang; Koehler, Maria; Slamon, Dennis

    2016-04-01

    randomly assigned, 347 to fulvestrant plus palbociclib and 174 to fulvestrant plus placebo. Study enrolment is closed and overall survival follow-up is in progress. By March 16, 2015, 259 progression-free-survival events had occurred (145 in the fulvestrant plus palbociclib group and 114 in the fulvestrant plus placebo group); median follow-up was 8·9 months (IQR 8·7-9·2). Median progression-free survival was 9·5 months (95% CI 9·2-11·0) in the fulvestrant plus palbociclib group and 4·6 months (3·5-5·6) in the fulvestrant plus placebo group (hazard ratio 0·46, 95% CI 0·36-0·59, p<0·0001). Grade 3 or 4 adverse events occurred in 251 (73%) of 345 patients in the fulvestrant plus palbociclib group and 38 (22%) of 172 patients in the fulvestrant plus placebo group. The most common grade 3 or 4 adverse events were neutropenia (223 [65%] in the fulvestrant plus palbociclib group and one [1%] in the fulvestrant plus placebo group), anaemia (ten [3%] and three [2%]), and leucopenia (95 [28%] and two [1%]). Serious adverse events (all causalities) occurred in 44 patients (13%) of 345 in the fulvestrant plus palbociclib group and 30 (17%) of 172 patients in the fulvestrant plus placebo group. PIK3CA mutation was detected in the plasma DNA of 129 (33%) of 395 patients for whom these data were available. Neither PIK3CA status nor hormone-receptor expression level significantly affected treatment response. Fulvestrant plus palboci