ERM immersion vaccination and adjuvants

DEFF Research Database (Denmark)

Skov, J.; Chettri, J. K.; Jaafar, R. M.

2015-01-01

Two candidate adjuvants were tested with a commercial ERM dip vaccine (AquaVac™ Relera, MSD Animal Health) for rainbow trout in an experimental design compatible with common vaccination practices at farm level, i.e. immersion of fish in vaccine (±adjuvant) for 30 s. The adjuvants were...... the commercial product Montanide™ IMS 1312 VG PR (SEPPIC), and a soluble and ≥98% pure β-glucan from yeast (Saccharomyces cerevisiae) (Sigma-Aldrich). Hence, five experimental groups in duplicate were established and exposed to vaccine and adjuvants in the following combinations: AquaVac™ Relera (alone); Aqua......Vac™ Relera + Montanide™; AquaVac™ Relera + β-glucan; Montanide™ (alone); and β-glucan (alone). Approximately 450 degree days post-vaccination, the fish were bath-challenged with live Yersinia ruckeri to produce survival curves. Blood, skin and gills were sampled at selected time points during the course...

Endogenous and Exogenous Natural Adjuvants for Vaccine Development.

Science.gov (United States)

Bolhassani, Azam; Talebi, Somayeh; Anvar, Ali

2017-01-01

Objective & Background: Various adjuvants are usually co-injected with an antigen for stimulation of effective immune responses. Adjuvants are able to elicit innate immune responses at the injection site. Depending on the activated type of innate responses, adjuvants can modify the quality and quantity of adaptive immune responses. Their mechanisms of action in vaccine development include: a) enhancement of the total antibody titers; b) reduction of the antigen dose; c) induction of potent cell-mediated immunity; d) increase in the speed and duration of the protective response; e) stimulation of mucosal immunity; and f) cross-protection. Up to now, different exogenous adjuvants have been identified to boost immune responses including inorganic compounds, mineral oil, bacterial products, non-bacterial organics, detergents or Quil A, plant saponins, Freund's complete or incomplete adjuvants, and delivery systems. However, some immune responses can be generated in the absence of the exogenous adjuvants. Indeed, endogenous adjuvants released from the cells were known as the danger signals and immunogenic compounds. Several main endogenous adjuvants contain cytokines, chemokines, alarmins, dendritic cells (DCs), toll like receptor (TLR) ligands or agonists, and antibodies. In this review, the immune activities of the natural adjuvants especially endogenous adjuvants and their mechanisms of action are discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Proteoliposome derived cochleate as novel adjuvant.

Science.gov (United States)

Bracho, Gustavo; Lastre, Miriam; del Campo, Judith; Zayas, Caridad; González, Domingo; Gil, Danay; Acevedo, Reinaldo; Taboada, Carlos; Solís, Rosa L; Pérez, Oliver

2006-04-12

Cochleate structures (CS) consist in a highly stable lipid structures that have been reported to be a good antigen delivery system. The incorporation of pathogen associated molecular pattern (PAMP) from bacterial membranes into CS became in a promising approach to develop adjuvants, particularly mucosal adjuvants. Therefore, we prepare CS from proteoliposome (PL) obtained from Neisseria meningitidis B (PLCS) and evaluated it for its capability to stimulate the immune system as well as the adjuvant activity. The ability of PLCS to induce Thl polarization was also explored. The results and the easy capability for new antigen incorporation on CS support its use as adjuvant for immunization with a large variety of pathogen derived antigens and different routes of immunization.

Applications of nanomaterials as vaccine adjuvants

Science.gov (United States)

Zhu, Motao; Wang, Rongfu; Nie, Guangjun

2014-01-01

Vaccine adjuvants are applied to amplify the recipient's specific immune responses against pathogen infection or malignancy. A new generation of adjuvants is being developed to meet the demands for more potent antigen-specific responses, specific types of immune responses, and a high margin of safety. Nanotechnology provides a multifunctional stage for the integration of desired adjuvant activities performed by the building blocks of tailor-designed nanoparticles. Using nanomaterials for antigen delivery can provide high bioavailability, sustained and controlled release profiles, and targeting and imaging properties resulting from manipulation of the nanomaterials’ physicochemical properties. Moreover, the inherent immune-regulating activity of particular nanomaterials can further promote and shape the cellular and humoral immune responses toward desired types. The combination of both the delivery function and immunomodulatory effect of nanomaterials as adjuvants is thought to largely benefit the immune outcomes of vaccination. In this review, we will address the current achievements of nanotechnology in the development of novel adjuvants. The potential mechanisms by which nanomaterials impact the immune responses to a vaccine and how physicochemical properties, including size, surface charge and surface modification, impact their resulting immunological outcomes will be discussed. This review aims to provide concentrated information to promote new insights for the development of novel vaccine adjuvants. PMID:25483497

Alginate: Current Use and Future Perspectives in Pharmaceutical and Biomedical Applications

Directory of Open Access Journals (Sweden)

Marta Szekalska

2016-01-01

Full Text Available Over the last decades, alginates, natural multifunctional polymers, have increasingly drawn attention as attractive compounds in the biomedical and pharmaceutical fields due to their unique physicochemical properties and versatile biological activities. The focus of the paper is to describe biological and pharmacological activity of alginates and to discuss the present use and future possibilities of alginates as a tool in drug formulation. The recent technological advancements with using alginates, issues related to alginates suitability as matrix for three-dimensional tissue cultures, adjuvants of antibiotics, and antiviral agents in cell transplantation in diabetes or neurodegenerative diseases treatment, and an update on the antimicrobial and antiviral therapy of the alginate based drugs are also highlighted.

Pharmaceutical films made from the waste material from the preparation of propolis extracts: development and characterization

Directory of Open Access Journals (Sweden)

Lucas de Alcântara Sica de Toledo

2015-12-01

Full Text Available abstract This study investigated the development and characterized the physicochemical properties of films obtained from by-products (BP from the preparation of propolis extracts. Films were produced in the presence and absence of a polymeric adjuvant (gelatin or ethylcellulose and propylene glycol by a solvent casting method. Density, surface topography by scanning electron microscopy, mechanical properties (folding endurance, tensile strength and percentage elongation, water vapour permeability (WVP, moisture uptake capacity, thermogravimetry, differential scanning calorimetry and Fourier transform infrared spectroscopy (FTIR were determined. The films were a transparent, light greenish-yellow colour, with a uniform surface, and were flexible and easy to handle. The thickness and density of the preparations indicated that the compounds were homogeneously dispersed throughout the film. Mechanical properties were influenced by the film composition; films containing gelatin were more resistant to stress, while those containing ethylcellulose were more flexible. Increasing the adjuvant concentration decreased the elasticity and the rupture resistance, but increased the moisture uptake capacity and WVP of the formulations. BP was thermally stable as were the films. FTIR tests suggested interactions between BP and the adjuvants. This work could contribute to the utilization of BP to prepare films for food and pharmaceutical uses

Adjuvant chemo- and radiotherapy in gastrointestinal tumors

International Nuclear Information System (INIS)

Sendler, A.; Feldmann, H.J.; Fink, U.; Molls, M.; Siewert, J.R.

1995-01-01

In modern surgical oncology, adjuvant therapies are important complementary strategies. In local advanced carcinomas of the gastrointestinal tract, 5-year survival data are still disappointing despite standardized surgery. In this context, it has to be differentiated between adjuvant therapy following complete tumor exstirpation (so-called UICC R 0 resection) and additive therapies following incomplete tumor resections (UICC R 1 or R 2 resection). Modalities in the adjuvant setting are chemotherapy, radiotherapy or the combined radio-/chemotherapy. In esophageal and gastric cancer there is up to now no benefit of postoperative adjuvant therapy. In pancreatic cancer, there are studies indicating a benefit of combined radio-/chemotherapy after complete tumor resection. A standard adjuvant chemotherapeutic treatment is proven in colon cancer stage III (Dukes C) with levamisole and 5-FU. Completely resected rectal carcinoma should be treated postoperatively with combined radio-/chemotherapy. In the common clinical or practical setting, adjuvant therapy is indicated only in locally advanced gastrointestinal tumors following R 0 resection. Postoperative therapy following incomplete tumor resection has its reason only in a palliative intention. (orig.) [de

Adjuvant chemotherapy for rectal cancer: Is it needed?

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Milinis, Kristijonas; Thornton, Michael; Montazeri, Amir; Rooney, Paul S

2015-01-01

Adjuvant chemotherapy has become a standard treatment of advanced rectal cancer in the West. The benefits of adjuvant chemotherapy after surgery alone have been well established. However, controversy surrounds the use adjuvant chemotherapy in patients who received preoperative chemoradiotherapy, despite it being recommended by a number of international guidelines. Results of recent multicentre randomised control trials showed no benefit of adjuvant chemotherapy in terms of survival and rates of distant metastases. However, concerns exist regarding the quality of the studies including inadequate staging modalities, out-dated chemotherapeutic regimens and surgical approaches and small sample sizes. It has become evident that not all the patients respond to adjuvant chemotherapy and more personalised approach should be employed when considering the benefits of adjuvant chemotherapy. The present review discusses the strengths and weaknesses of the current evidence-base and suggests improvements for future studies. PMID:26677436

Synthetic Self-Adjuvanting Glycopeptide Cancer Vaccines

Science.gov (United States)

Payne, Richard; McDonald, David; Byrne, Scott

2015-10-01

Due to changes in glycosyltransferase expression during tumorigenesis, the glycoproteins of cancer cells often carry highly truncated carbohydrate chains compared to those on healthy cells. These glycans are known as tumor-associated carbohydrate antigens, and are prime targets for use in vaccines for the prevention and treatment of cancer. Herein, we review the state-of-the-art in targeting the immune system towards tumor-associated glycopeptide antigens via synthetic self adjuvanting vaccines, in which the antigenic and adjuvanting moieties of the vaccines are present in the same molecule. The majority of the self-adjuvanting glycopeptide cancer vaccines reported to date employ antigens from mucin 1, a protein which is highly over-expressed and aberrantly glycosylated in many forms of cancer. The adjuvants used in these vaccines predominantly include lipopeptide- or lipoamino acid-based TLR2 agonists, although studies investigating stimulation of TLR9 and TLR4 are also discussed. Most of these adjuvants are highly lipophilic, and, upon conjugation to antigenic peptides, provide amphiphilic vaccine molecules. The amphiphilic nature of these vaccine constructs can lead to the formation of higher-order structures by vaccines in solution, which are likely to be important for their efficacy in vivo.

BROMATOMATRIC ASSAY OF GATIFLOXACIN IN PHARMACEUTICALS

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KALSANG THARPA

2008-09-01

Full Text Available Three new, simple, and cost-effective visible spectrophotometric methods are proposed for determination of gatifloxacin (GTF using bromate-bromide mixture, and three dyes, methyl orange, indigocarmine and thymol blue, as reagents.The methods engross the addition of a known excess of bromate-bromide mixture to GTF in hydrochloric acid medium followed by determination of residual bromine by reacting with a fixed amount of either methyl orange andmeasuring the absorbance at 520 nm (method A or indigo carmine and measuring the absorbance at 610 nm (method B or thymol blue and measuring the absorbance at 550 nm (method C. In all the methods, the amount of brominereacted corresponds to the amount of GTF, and the absorbance is found to increase linearly with the concentration of GTF. Under the optimum conditions, GTF could be assayed in the concentration range 0.25-1.5, 0.5-6.0, and 0.5-10μg/mL by method A, method B and method C, respectively. The apparent molar absorptivities are calculated to be 1.6x105, 4.0x104 and 3.2x104 L mol-1 cm-1 for the method A, method B and method C, respectively, and the corresponding Sandell sensitivity values are 0.0025, 0.010 and 0.012 μg/cm2. The intra-day and inter-day precision, and the accuracy of the methods were evaluated as per the current ICH guidelines. The methods were successfully applied to the determination of GTF in pharmaceutical preparations without the interference from any of the pharmaceutical adjuvants.

Quantification of Multiple Components of Complex Aluminum-Based Adjuvant Mixtures by Using Fourier Transform Infrared Spectroscopy and Partial Least Squares Modeling.

Science.gov (United States)

Dowling, Quinton M; Kramer, Ryan M

2017-01-01

Fourier transform infrared (FTIR) spectroscopy is widely used in the pharmaceutical industry for process monitoring, compositional quantification, and characterization of critical quality attributes in complex mixtures. Advantages over other spectroscopic measurements include ease of sample preparation, quantification of multiple components from a single measurement, and the ability to quantify optically opaque samples. This method describes the use of a multivariate model for quantifying a TLR4 agonist (GLA) adsorbed onto aluminum oxyhydroxide (Alhydrogel ® ) using FTIR spectroscopy that may be adapted to quantify other complex aluminum based adjuvant mixtures.

Novel Adjuvants and Immunomodulators for Veterinary Vaccines.

Science.gov (United States)

Heegaard, Peter M H; Fang, Yongxiang; Jungersen, Gregers

2016-01-01

Adjuvants are crucial for efficacy of vaccines, especially subunit and recombinant vaccines. Rational vaccine design, including knowledge-based and molecularly defined adjuvants tailored for directing and potentiating specific types of host immune responses towards the antigens included in the vaccine is becoming a reality with our increased understanding of innate and adaptive immune activation. This will allow future vaccines to induce immune reactivity having adequate specificity as well as protective and recallable immune effector mechanisms in appropriate body compartments, including mucosal surfaces. Here we describe these new developments and, when possible, relate new immunological knowledge to the many years of experience with traditional, empirical adjuvants. Finally, some protocols are given for production of emulsion (oil-based) and liposome-based adjuvant/antigen formulations.

Adjuvant chemotherapy and cancer cure

International Nuclear Information System (INIS)

Bertino, J.R.

1983-01-01

The use of chemotherapy as an adjuvant to surgery and/or radiotherapy is well founded in experimental tumor systems and appears to be effective in patients in some circumstances. It is clear from both clinical and experimental studies that (1) the dose is important, (2) the earlier chemotherapy is started after primary therapy the better, and (3) combination chemotherapy may be more effective than single-agent treatment. The better the estimation of risk of recurrence, the better the assessment of the risk-benefit ratio with adjuvant therapy. Salvage therapy as well as relative risk of recurrence are considerations in the choice of patients to be treated. Finally, some evidence is presented to indicate that alkylating agents may not be necessary in combination regimens for adjuvant therapy if effective antimetabolite combinations are available

The Pharmaceutical Industry Beamline of Pharmaceutical Consortium for Protein Structure Analysis

International Nuclear Information System (INIS)

Nishijima, Kazumi; Katsuya, Yoshio

2002-01-01

The Pharmaceutical Industry Beamline was constructed by the Pharmaceutical Consortium for Protein Structure Analysis which was established in April 2001. The consortium is composed of 22 pharmaceutical companies affiliating with the Japan Pharmaceutical Manufacturers Association. The beamline is the first exclusive on that is owned by pharmaceutical enterprises at SPring-8. The specification and equipments of the Pharmaceutical Industry Beamline is almost same as that of RIKEN Structural Genomics Beamline I and II. (author)

Modern Vaccines/Adjuvants Formulation—Session 2 (Plenary II)

Science.gov (United States)

Collin, Nicolas

2013-01-01

On the 15–17th May 2013, the Fourth International Conference on Modern Vaccines/Adjuvants Formulation was organized in Lausanne, Switzerland, and gathered stakeholders from academics and from the industry to discuss several challenges, advances and promises in the field of vaccine adjuvants. Plenary session 2 of the meeting was composed of four different presentations covering: (1) the recent set-up of an adjuvant technology transfer and training platform in Switzerland, (2) the proposition to revisit existing paradigms of modern vaccinology, (3) the properties of polyethyleneimine as potential new vaccine adjuvant, and (4) the progresses in the design of HIV vaccine candidates able to induce broadly neutralizing antibodies. PMID:23966098

Adjuvant radiation for vulvar carcinoma: improved local control

International Nuclear Information System (INIS)

Faul, Clare M.; Mirmow, Dwight; Huang Qingshon; Gerszten, Kristina; Day, Roger; Jones, Mirka W.

1997-01-01

Purpose: Local recurrence is a significant problem following primary surgery for advanced vulva carcinoma. The objectives of this study were to evaluate the impact of adjuvant vulvar radiation on local control in high risk patients and the impact of local recurrence on overall survival. Methods and Materials: From 1980-1994, 62 patients with invasive vulva carcinoma and either positive or close (less 8 mm) margins of excision were retrospectively studied. Thirty-one patients were treated with adjuvant radiation therapy to the vulva and 31 patients were observed after surgery. Kaplan-Meier estimates and the Cox proportional hazard regression model were used to evaluate the effect of adjuvant radiation therapy on local recurrence and overall survival. Independent prognostic factors for local recurrence and survival were also assessed. Results: Local recurrence occurred in 58% of observed patients and 16% in patients treated with adjuvant radiation therapy. Adjuvant radiation therapy significantly reduced local recurrence rates in both the close margin and positive margin groups (p = 0.036, p = 0.0048). On both univariate and multivariate analysis adjuvant radiation and margins of excision were significant prognostic predictors for local control. Significant determinants of actuarial survival included International Federation of Gynecologists and Obstetricians (FIGO) stage, percentage of pathologically positive inguinal nodes and margins of excision. The positive margin observed group had a significantly poorer actuarial 5 year survival than the other groups (p = 0.0016) and adjuvant radiation significantly improved survival for this group. The 2 year actuarial survival after developing local recurrence was 25%. Local recurrence was a significant predictor for death from vulva carcinoma (risk ratio 3.54). Conclusion: Local recurrence is a common occurrence in high risk patients. In this study adjuvant radiation therapy significantly reduced local recurrence rates and

An update on safety and immunogenicity of vaccines containing emulsion-based adjuvants.

Science.gov (United States)

Fox, Christopher B; Haensler, Jean

2013-07-01

With the exception of alum, emulsion-based vaccine adjuvants have been administered to far more people than any other adjuvant, especially since the 2009 H1N1 influenza pandemic. The number of clinical safety and immunogenicity evaluations of vaccines containing emulsion adjuvants has correspondingly mushroomed. In this review, the authors introduce emulsion adjuvant composition and history before detailing the most recent findings from clinical and postmarketing data regarding the effects of emulsion adjuvants on vaccine immunogenicity and safety, with emphasis on the most widely distributed emulsion adjuvants, MF59® and AS03. The authors also present a summary of other emulsion adjuvants in clinical development and indicate promising avenues for future emulsion-based adjuvant development. Overall, emulsion adjuvants have demonstrated potent adjuvant activity across a number of disease indications along with acceptable safety profiles.

Overview of Vaccine Adjuvants: Introduction, History, and Current Status.

Science.gov (United States)

Shah, Ruchi R; Hassett, Kimberly J; Brito, Luis A

2017-01-01

Adjuvants are included in sub-unit or recombinant vaccines to enhance the potency of poorly immunogenic antigens. Adjuvant discovery is as complex as it is a multidiscplinary intersection of formulation science, immunology, toxicology, and biology. Adjuvants such as alum, which have been in use for the past 90 years, have illustrated that adjuvant research is a methodical process. As science advances, new analytical tools are developed which allows us to delve deeper into the various mechanisms that generates a potent immune response. Additionally, these new techniques help the field learn about our existing vaccines and what makes them safe, and effective, allowing us to leverage that in the next generation of vaccines. Our goal in this chapter is to define the concept, need, and mechanism of adjuvants in the vaccine field while describing its history, present use, and future prospects. More details on individual adjuvants and their formulation, development, mechanism, and use will be covered in depth in the next chapters.

Does lipophilicity per se induce adjuvant effects?

DEFF Research Database (Denmark)

Hansen, Jitka Stilund; Larsen, Søren Thor; Poulsen, Lars K.

2007-01-01

Anthopogenically introduced substances and pollutants are suspected to promote sensitization and development of allergic airway diseases, that is, acting as adjuvants. Lipophilicity may serve as an immunological warning signal, promoting adjuvant effects. Whether the lipophilicity of an inhaled...... respiratory patterns were significantly affected in the MP groups. The OVA + Al(OH)3 group had a significantly higher IgG1 and IgE production, as well as higher eosinophil infiltration in the BAL fluid. These studies showed that effects of adjuvants not are necessarily due to their lipophilicity; that is...

Novel Adjuvants and Immunomodulators for Veterinary Vaccines

DEFF Research Database (Denmark)

Heegaard, Peter M. H.; Fang, Yongxiang; Jungersen, Gregers

2016-01-01

Adjuvants are crucial for efficacy of vaccines, especially subunit and recombinant vaccines. Rational vaccine design, including knowledge-based and molecularly defined adjuvants tailored for directing and potentiating specific types of host immune responses towards the antigens included in the va...

Antibody-antigen-adjuvant conjugates enable co-delivery of antigen and adjuvant to dendritic cells in cis but only have partial targeting specificity.

Directory of Open Access Journals (Sweden)

Martin Kreutz

Full Text Available Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is paramount. However, co-administration of unlinked adjuvant cannot ensure that all cells targeted by the antibody conjugates are appropriately activated. Furthermore, antigen-presenting cells (APC that do not present the desired antigen are equally strongly activated and could prime undesired responses against self-antigens. We, therefore, were interested in exploring targeted co-delivery of antigen and adjuvant in cis in form of antibody-antigen-adjuvant conjugates for the induction of anti-tumour immunity. In this study, we report on the assembly and characterization of conjugates consisting of DEC205-specific antibody, the model antigen ovalbumin (OVA and CpG oligodeoxynucleotides (ODN. We show that such conjugates are more potent at inducing cytotoxic T lymphocyte (CTL responses than control conjugates mixed with soluble CpG. However, our study also reveals that the nucleic acid moiety of such antibody-antigen-adjuvant conjugates alters their binding and uptake and allows delivery of the antigen and the adjuvant to cells partially independently of DEC205. Nevertheless, antibody-antigen-adjuvant conjugates are superior to antibody-free antigen-adjuvant conjugates in priming CTL responses and efficiently induce anti-tumour immunity in the murine B16 pseudo-metastasis model. A better understanding of the role of the antibody moiety is required to inform future conjugate vaccination strategies for efficient induction of anti-tumour responses.

Towards an understanding of the adjuvant action of aluminium

Science.gov (United States)

Marrack, Philippa; McKee, Amy S.; Munks, Michael W.

2011-01-01

The efficacy of vaccines depends on the presence of an adjuvant in conjunction with the antigen. Of these adjuvants, the ones that contain aluminium, which were first discovered empirically in 1926, are currently the most widely used. However, a detailed understanding of their mechanism of action has only started to be revealed. In this Timeline article, we briefly describe the initial discovery of aluminium adjuvants and discuss historically important advances. We also summarize recent progress in the field and discuss their implications and the remaining questions on how these adjuvants work. PMID:19247370

Adjuvants for vaccines to drugs of abuse and addiction.

Science.gov (United States)

Alving, Carl R; Matyas, Gary R; Torres, Oscar; Jalah, Rashmi; Beck, Zoltan

2014-09-22

Immunotherapeutic vaccines to drugs of abuse, including nicotine, cocaine, heroin, oxycodone, methamphetamine, and others are being developed. The theoretical basis of such vaccines is to induce antibodies that sequester the drug in the blood in the form of antibody-bound drug that cannot cross the blood brain barrier, thereby preventing psychoactive effects. Because the drugs are haptens a successful vaccine relies on development of appropriate hapten-protein carrier conjugates. However, because induction of high and prolonged levels of antibodies is required for an effective vaccine, and because injection of T-independent haptenic drugs of abuse does not induce memory recall responses, the role of adjuvants during immunization plays a critical role. As reviewed herein, preclinical studies often use strong adjuvants such as complete and incomplete Freund's adjuvant and others that cannot be, or in the case of many newer adjuvants, have never been, employed in humans. Balanced against this, the only adjuvant that has been included in candidate vaccines in human clinical trials to nicotine and cocaine has been aluminum hydroxide gel. While aluminum salts have been widely utilized worldwide in numerous licensed vaccines, the experience with human responses to aluminum salt-adjuvanted vaccines to haptenic drugs of abuse has suggested that the immune responses are too weak to allow development of a successful vaccine. What is needed is an adjuvant or combination of adjuvants that are safe, potent, widely available, easily manufactured, and cost-effective. Based on our review of the field we recommend the following adjuvant combinations either for research or for product development for human use: aluminum salt with adsorbed monophosphoryl lipid A (MPLA); liposomes containing MPLA [L(MPLA)]; L(MPLA) adsorbed to aluminum salt; oil-in-water emulsion; or oil-in-water emulsion containing MPLA. Copyright © 2014. Published by Elsevier Ltd.

Production, purification and immunogenicity of recombinant Ebola virus proteins - A comparison of Freund's adjuvant and adjuvant system 03.

Science.gov (United States)

Melén, Krister; Kakkola, Laura; He, Felix; Airenne, Kari; Vapalahti, Olli; Karlberg, Helen; Mirazimi, Ali; Julkunen, Ilkka

2017-04-01

There is an urgent need for Ebola virus (EBOV) proteins, EBOV-specific antibodies and recombinant antigens to be used in diagnostics and as potential vaccine candidates. Our objective was to produce and purify recombinant proteins for immunological assays and for the production of polyclonal EBOV specific antibodies. In addition, a limited comparison of the adjuvant effects of Freund's complete adjuvant (FCA) and adjuvant system 03 (AS03) was carried out. Recombinant EBOV GST-VP24, -VP30, -VP35, -VP40 and -NP were produced in E. coli and purified with affinity chromatography followed by preparative gel electrophoresis. Recombinant EBOV GP-His was produced in Sf9 insect cells and purified by preparative gel electrophoresis. To compare the adjuvant effect of FCA and AS03, 12 rabbits were immunized four times with one of the six recombinant EBOV proteins using FCA or AS03. In addition, three guinea pigs were immunized with EBOV VP24 using FCA. With the exception of sera from two rabbits immunized with GST-VP24, the antisera against all other EBOV proteins showed very high and specific antibody responses after three to four immunizations. The adjuvant effect of AS03 was comparable to that of FCA. The produced antibodies recognized the corresponding EBOV proteins in wild type EBOV-infected cells. Copyright © 2016 Elsevier B.V. All rights reserved.

Immunomodulators as adjuvants for vaccines and antimicrobial therapy.

Science.gov (United States)

Nicholls, Erin F; Madera, Laurence; Hancock, Robert E W

2010-12-01

A highly effective strategy for combating infectious diseases is to enhance host defenses using immunomodulators, either preventatively, through vaccination, or therapeutically. The effectiveness of many vaccines currently in use is due in part to adjuvants, molecules that have little immunogenicity by themselves but which help enhance and appropriately skew the immune response to an antigen. The development of new vaccines necessitates the development of new types of adjuvants to ensure an appropriate immune response. Herein, we review commonly used vaccine adjuvants and discuss promising adjuvant candidates. We also discuss various other immunomodulators (namely cytokines, Toll-like receptor agonists, and host defense peptides) that are, or have potential to be, useful for antimicrobial therapies that exert their effects by boosting host immune responses rather than targeting pathogens directly.

Basic pharmaceutical technology

OpenAIRE

Angelovska, Bistra; Drakalska, Elena

2017-01-01

The lecture deals with basics of pharmaceutical technology as applied discipline of pharmaceutical science, whose main subject of study is formulation and manufacture of drugs. In a broad sense, pharmaceutical technology is science of formulation, preparation, stabilization and determination of the quality of medicines prepared in the pharmacy or in pharmaceutical industry

House dust extracts contain potent immunological adjuvants

NARCIS (Netherlands)

Beukelman, C.J.; Dijk, H. van; Aerts, P.C.; Rademaker, P.M.; Berrens, L.; Willers, J.M.N.

1987-01-01

A crude aqueous extract of house dust and two house dust subfractions were tested for adjuvant activity in a sensitivity assay performed in mice. Evidence is presented that house dust contains at least two potent immunological adjuvants. One of these, present in both subfractions, was probably

Intranasal Immunization Using Mannatide as a Novel Adjuvant for an Inactivated Influenza Vaccine and Its Adjuvant Effect Compared with MF59.

Directory of Open Access Journals (Sweden)

Shu-Ting Ren

Full Text Available Intranasal vaccination is more potent than parenteral injection for the prevention of influenza. However, because the poor efficiency of antigen uptake across the nasal mucosa is a key issue, immunostimulatory adjuvants are essential for intranasal vaccines. The immunomodulator mannatide or polyactin (PA has been used for the clinical treatment of impaired immunity in China, but its adjuvant effect on an inactivated trivalent influenza vaccine (ITIV via intranasal vaccination is unclear. To explore the adjuvant effect of PA, an inactivated trivalent influenza virus with or without PA or MF59 was instilled intranasally once a week in BALB/c mice. Humoral immunity was assessed by both the ELISA and hemagglutination inhibition (HI methods using antigen-specific antibodies. Splenic lymphocyte proliferation and the IFN-γ level were measured to evaluate cell-mediated immunity. The post-vaccination serum HI antibody geometric mean titers (GMTs for the H1N1 and H3N2 strains, antigen-specific serum IgG and IgA GMTs, mucosal SIgA GMT, splenic lymphocyte proliferation, and IFN-γ were significantly increased in the high-dose PA-adjuvanted vaccine group. The seroconversion rate and the mucosal response for the H3N2 strain were significantly elevated after high-dose PA administration. These adjuvant effects of high-dose PA for the influenza vaccine were comparable with those of the MF59 adjuvant, and abnormal signs or pathological changes were not found in the evaluated organs. In conclusion, PA is a novel mucosal adjuvant for intranasal vaccination with the ITIV that has safe and effective mucosal adjuvanticity in mice and successfully induces both serum and mucosal antibody responses and a cell-mediated response.

Adjuvant solution for pandemic influenza vaccine production.

Science.gov (United States)

Clegg, Christopher H; Roque, Richard; Van Hoeven, Neal; Perrone, Lucy; Baldwin, Susan L; Rininger, Joseph A; Bowen, Richard A; Reed, Steven G

2012-10-23

Extensive preparation is underway to mitigate the next pandemic influenza outbreak. New vaccine technologies intended to supplant egg-based production methods are being developed, with recombinant hemagglutinin (rHA) as the most advanced program for preventing seasonal and avian H5N1 Influenza. Increased efforts are being focused on adjuvants that can broaden vaccine immunogenicity against emerging viruses and maximize vaccine supply on a worldwide scale. Here, we test protection against avian flu by using H5N1-derived rHA and GLA-SE, a two-part adjuvant system containing glucopyranosyl lipid adjuvant (GLA), a formulated synthetic Toll-like receptor 4 agonist, and a stable emulsion (SE) of oil in water, which is similar to the best-in-class adjuvants being developed for pandemic flu. Notably, a single submicrogram dose of rH5 adjuvanted with GLA-SE protects mice and ferrets against a high titer challenge with H5N1 virus. GLA-SE, relative to emulsion alone, accelerated induction of the primary immune response and broadened its durability against heterosubtypic H5N1 virus challenge. Mechanistically, GLA-SE augments protection via induction of a Th1-mediated antibody response. Innate signaling pathways that amplify priming of Th1 CD4 T cells will likely improve vaccine performance against future outbreaks of lethal pandemic flu.

The adjuvant potential of synthetic alkylglycerols.

Science.gov (United States)

Acevedo, Reinaldo; Gil, Danay; del Campo, Judith; Bracho, Gustavo; Valdés, Yolanda; Pérez, Oliver

2006-04-12

Alkylglycerols (AGs) have shown immune stimulant and adjuvant activity in many studies, but natural sources are not so accessible and their extraction from them is very complicated. Therefore, a group of chemists at IFAL have synthesized AG analogs. The aim of this work was to evaluate the adjuvant potential of different synthetic AGs. A mix of ovoalbumin (Ova) and AGs increase anti-Ova IgG antibodies production in sera of immunized mice. The predominant subclass was IgG1 although higher levels of IgG2a were observed as the carbon chain length of AGs increased. AGs also induced the production of IL-12 and nitric oxide (NO) in the U937 human histiocyte and J774 mouse macrophage cell lines, respectively. These results indicate that synthetic AGs are effective adjuvants for the standardized antigen, Ova.

An overview of adjuvants utilized in prophylactic vaccine formulation as immunomodulators.

Science.gov (United States)

Chauhan, Nidhi; Tiwari, Sukirti; Iype, Tessy; Jain, Utkarsh

2017-05-01

Development of efficient and cost effective vaccines have been recognized as the primary concern to improve the overall healthcare in a country. In order to achieve this goal, more improved and powerful adjuvants need to be developed. Lacking in the self-adjuvanting immuno-modulatory constituents, vaccines exhibit lower immunogenicity. Combining potent adjuvants with vaccines is the most appropriate method to enhance the efficacy of the vaccines. Hence, this review is focussed on the most potent adjuvants for the formulation of vaccines. Areas covered: This review focuses on Oil-based emulsions, Mineral compounds, Liposomes, Bacterial products, ISCOMs and most recently used nanomaterials as adjuvants for enhancing the antigenicity of vaccines. Furthermore, this review explains the immunological response elicited by various particles. Moreover, case studies are incorporated providing an in depth analyses of various adjuvant-containing vaccines which are currently used. Expert commentary: Enhanced fundamental knowledge about the adjuvants and their immuno-stimulatory capabilities and delivery mechanisms will facilitate the rational designing of prophylactic vaccines with better efficacy.

Environmental adjuvants, apoptosis and the censorship over autoimmunity.

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Rovere-Querini, Patrizia; Manfredi, Angelo A; Sabbadini, Maria Grazia

2005-11-01

Alterations during apoptosis lead to the activation of autoreactive T cells and the production of autoantibodies. This article discusses the pathogenic potential of cells dying in vivo, dissecting the role of signals that favor immune responses (adjuvants) and the influence of genetic backgrounds. Diverse factors determine whether apoptosis leads or not to a self-sustaining, clinically apparent autoimmune disease. The in vivo accumulation of uncleared dying cells per se is not sufficient to cause disease. However, dying cells are antigenic and their complementation with immune adjuvants causes lethal diseases in predisposed lupus-prone animals. At least some adjuvant signals directly target the function and the activation state of antigen presenting cells. Several laboratories are aggressively pursuing the molecular identification of endogenous adjuvants. Sodium monourate and the high mobility group B1 protein (HMGB1) are, among those identified so far, well known to rheumatologists. However, even the complementation of apoptotic cells with potent adjuvant signals fail to cause clinical autoimmunity in most strains: autoantibodies generated are transient, do not undergo to epitope/spreading and do not cause disease. Novel tools for drug development will derive from the molecular identification of the constraints that prevent autoimmunity in normal subjects.

Adjuvant Therapy for Gallbladder Carcinoma: The Mayo Clinic Experience

International Nuclear Information System (INIS)

Gold, Douglas G.; Miller, Robert C.; Haddock, Michael G.; Gunderson, Leonard L.; Quevedo, Fernando; Donohue, John H.; Bhatia, Sumita; Nagorney, David M.

2009-01-01

Purpose: To analyze the effect of adjuvant chemoradiotherapy on gallbladder carcinoma. Methods and Materials: We retrospectively reviewed the records from consecutive patients who underwent R0 resection of gallbladder carcinoma between January 1, 1985, and December 31, 2004. Patients had either Stage I (T1-T2N0M0) or Stage II (T3N0M0 or T1-T3N1M0) disease. Patients undergoing adjuvant therapy received 5-fluorouracil chemotherapy concurrently with radiotherapy (median dosage, 50.4 Gy in 28 fractions). Adverse prognostic factors and the effect of adjuvant treatment on overall survival (OS) were evaluated. Results: A total of 73 patients were included in the analysis; of these, 25 received adjuvant chemoradiotherapy. On univariate analysis, no adverse prognostic factors for OS reached statistical significance, but trends were noted for Stage N1 vs. N0 (p = .06), Nx vs. N0 (p = .09), Stage T3 vs. T1-T2 (p = .06), and histologic findings other than adenocarcinoma (p = .13). The median OS for patients receiving adjuvant chemoradiotherapy vs. surgery alone was 4.8 years and 4.2 years, respectively (log-rank test, p = .56). However, a significantly greater percentage of patients receiving adjuvant chemoradiotherapy had Stage II disease (p <.001). In the multivariate Cox model, increasing T and N category and histologic findings other than adenocarcinoma were significant predictors of decreased OS. Additionally, adjuvant chemoradiotherapy was a significant predictor of improved OS after adjusting for these prognostic factors (hazard ratio for death, 0.3; 95% confidence interval, 0.13-0.69; p = .004). Conclusion: After adjusting for the stage parameters and histologic findings, our data suggest that adjuvant chemoradiotherapy might improve OS for patients with gallbladder cancer.

Predictive markers of safety and immunogenicity of adjuvanted vaccines.

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Mastelic, Beatris; Garçon, Nathalie; Del Giudice, Giuseppe; Golding, Hana; Gruber, Marion; Neels, Pieter; Fritzell, Bernard

2013-11-01

Vaccination represents one of the greatest public health triumphs; in part due to the effect of adjuvants that have been included in vaccine preparations to boost the immune responses through different mechanisms. Although a variety of novel adjuvants have been under development, only a limited number have been approved by regulatory authorities for human vaccines. This report reflects the conclusions of a group of scientists from academia, regulatory agencies and industry who attended a conference on the current state of the art in the adjuvant field. Held at the U.S. Pharmacopeial Convention (USP) in Rockville, Maryland, USA, from 18 to 19 April 2013 and organized by the International Association for Biologicals (IABS), the conference focused particularly on the future development of effective adjuvants and adjuvanted vaccines and on overcoming major hurdles, such as safety and immunogenicity assessment, as well as regulatory scrutiny. More information on the conference output can be found on the IABS website, http://www.iabs.org/. Copyright © 2013. Published by Elsevier Ltd.. All rights reserved.

GLA-AF, an emulsion-free vaccine adjuvant for pandemic influenza.

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Clegg, Christopher H; Roque, Richard; Perrone, Lucy A; Rininger, Joseph A; Bowen, Richard; Reed, Steven G

2014-01-01

The ongoing threat from Influenza necessitates the development of new vaccine and adjuvant technologies that can maximize vaccine immunogenicity, shorten production cycles, and increase global vaccine supply. Currently, the most successful adjuvants for Influenza vaccines are squalene-based oil-in-water emulsions. These adjuvants enhance seroprotective antibody titers to homologous and heterologous strains of virus, and augment a significant dose sparing activity that could improve vaccine manufacturing capacity. As an alternative to an emulsion, we tested a simple lipid-based aqueous formulation containing a synthetic TLR4 ligand (GLA-AF) for its ability to enhance protection against H5N1 infection. GLA-AF was very effective in adjuvanting recombinant H5 hemagglutinin antigen (rH5) in mice and was as potent as the stable emulsion, SE. Both adjuvants induced similar antibody titers using a sub-microgram dose of rH5, and both conferred complete protection against a highly pathogenic H5N1 challenge. However, GLA-AF was the superior adjuvant in ferrets. GLA-AF stimulated a broader antibody response than SE after both the prime and boost immunization with rH5, and ferrets were better protected against homologous and heterologous strains of H5N1 virus. Thus, GLA-AF is a potent emulsion-free adjuvant that warrants consideration for pandemic influenza vaccine development.

Long-term heart function after adjuvant epirubicin chemotherapy for breast cancer

DEFF Research Database (Denmark)

Appel, Jon M; Zerahn, Bo; Møller, Susanne

2012-01-01

Newer studies raise concern that adjuvant anthracycline treatment for breast cancer (BC) causes long-term heart damage. We aimed to examine whether heart failure or impairment could be demonstrated several years after low-dose epirubicin-based adjuvant treatment.......Newer studies raise concern that adjuvant anthracycline treatment for breast cancer (BC) causes long-term heart damage. We aimed to examine whether heart failure or impairment could be demonstrated several years after low-dose epirubicin-based adjuvant treatment....

Adjuvant Biological Therapies in Chronic Leg Ulcers

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Natalia Burgos-Alonso

2017-11-01

Full Text Available Current biological treatments for non-healing wounds aim to address the common deviations in healing mechanisms, mainly inflammation, inadequate angiogenesis and reduced synthesis of extracellular matrix. In this context, regenerative medicine strategies, i.e., platelet rich plasmas and mesenchymal stromal cell products, may form part of adjuvant interventions in an integral patient management. We synthesized the clinical experience on ulcer management using these two categories of biological adjuvants. The results of ten controlled trials that are included in this systematic review favor the use of mesenchymal stromal cell based-adjuvants for impaired wound healing, but the number and quality of studies is moderate-low and are complicated by the diversity of biological products. Regarding platelet-derived products, 18 controlled studies investigated their efficacy in chronic wounds in the lower limb, but the heterogeneity of products and protocols hinders clinically meaningful quantitative synthesis. Most patients were diabetic, emphasizing an unmet medical need in this condition. Overall, there is not sufficient evidence to inform routine care, and further clinical research is necessary to realize the full potential of adjuvant regenerative medicine strategies in the management of chronic leg ulcers.

Adjuvant therapy for ampullary carcinomas: The Mayo Clinic experience

International Nuclear Information System (INIS)

Bhatia, Sumita; Miller, Robert C.; Haddock, Michael G.; Donohue, John H.; Krishnan, Sunil

2006-01-01

Purpose: To determine the effects of adjuvant radiotherapy and chemotherapy for carcinoma of the ampulla of Vater. Methods and Materials: We retrospectively reviewed the records of 125 patients who underwent definitive surgery for carcinomas involving the ampulla of Vater between April 1977 and February 2005 and who survived more than 50 days after surgery. Twenty-nine of the patients also received adjuvant radiotherapy (median dose, 50.4 Gy in 28 fractions) with concurrent 5-fluorouracil chemotherapy. Adverse prognostic factors were investigated, and overall survival (OS) and local and distant failure were estimated. Results: Adverse prognostic factors for decreased OS by univariate analysis included lymph node (LN) involvement, locally advanced tumors (T3/T4), and poor histologic grade. By multivariate analysis, positive LN status (p = 0.02) alone was associated with decreased OS. The addition of adjuvant radiotherapy and chemotherapy improved OS for patients with positive LN (p = 0.01). Median survival for positive LN patients receiving adjuvant therapy was 3.4 years, vs. 1.6 years for those with surgery alone. Conclusions: The addition of adjuvant radiotherapy and 5-fluorouracil chemotherapy may improve OS in patients with LN involvement. The effect of adjuvant therapy on outcomes for patients with poor histologic grade or T3/T4 tumors without LN involvement could not be assessed

Antigen sparing with adjuvanted inactivated polio vaccine based on Sabin strains.

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Westdijk, Janny; Koedam, Patrick; Barro, Mario; Steil, Benjamin P; Collin, Nicolas; Vedvick, Thomas S; Bakker, Wilfried A M; van der Ley, Peter; Kersten, Gideon

2013-02-18

Six different adjuvants, each in combination with inactivated polio vaccine (IPV) produced with attenuated Sabin strains (sIPV), were evaluated for their ability to enhance virus neutralizing antibody titres (VNTs) in the rat potency model. The increase of VNTs was on average 3-, 15-, 24-fold with adjuvants after one immunization (serotypes 1, 2, and 3, respectively). Also after a boost immunization the VNTs of adjuvanted sIPV were on average another 7-20-27 times higher than after two inoculations of sIPV without adjuvant. The results indicate that it is feasible to increase the potency of inactivated polio vaccines by using adjuvants. Copyright © 2013 Elsevier Ltd. All rights reserved.

Laser vaccine adjuvants. History, progress, and potential.

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Kashiwagi, Satoshi; Brauns, Timothy; Gelfand, Jeffrey; Poznansky, Mark C

2014-01-01

Immunologic adjuvants are essential for current vaccines to maximize their efficacy. Unfortunately, few have been found to be sufficiently effective and safe for regulatory authorities to permit their use in vaccines for humans and none have been approved for use with intradermal vaccines. The development of new adjuvants with the potential to be both efficacious and safe constitutes a significant need in modern vaccine practice. The use of non-damaging laser light represents a markedly different approach to enhancing immune responses to a vaccine antigen, particularly with intradermal vaccination. This approach, which was initially explored in Russia and further developed in the US, appears to significantly improve responses to both prophylactic and therapeutic vaccines administered to the laser-exposed tissue, particularly the skin. Although different types of lasers have been used for this purpose and the precise molecular mechanism(s) of action remain unknown, several approaches appear to modulate dendritic cell trafficking and/or activation at the irradiation site via the release of specific signaling molecules from epithelial cells. The most recent study, performed by the authors of this review, utilized a continuous wave near-infrared laser that may open the path for the development of a safe, effective, low-cost, simple-to-use laser vaccine adjuvant that could be used in lieu of conventional adjuvants, particularly with intradermal vaccines. In this review, we summarize the initial Russian studies that have given rise to this approach and comment upon recent advances in the use of non-tissue damaging lasers as novel physical adjuvants for vaccines.

Chemokines as Cancer Vaccine Adjuvants

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Agne Petrosiute

2013-10-01

Full Text Available We are witnessing a new era of immune-mediated cancer therapies and vaccine development. As the field of cancer vaccines advances into clinical trials, overcoming low immunogenicity is a limiting step in achieving full success of this therapeutic approach. Recent discoveries in the many biological roles of chemokines in tumor immunology allow their exploitation in enhancing recruitment of antigen presenting cells (APCs and effector cells to appropriate anatomical sites. This knowledge, combined with advances in gene therapy and virology, allows researchers to employ chemokines as potential vaccine adjuvants. This review will focus on recent murine and human studies that use chemokines as therapeutic anti-cancer vaccine adjuvants.

AS03-adjuvanted versus non-adjuvanted inactivated trivalent influenza vaccine against seasonal influenza in elderly people: a phase 3 randomised trial

NARCIS (Netherlands)

McElhaney, J.E.; Beran, J.; Devaster, J.M.; Esen, M.; Launay, O.; Leroux-Roels, G.; Ruiz-Palacios, G.M.; Essen, G.A. van; Caplanusi, A.; Claeys, C.; Durand, C.; Duval, X.; Idrissi, M. El; Falsey, A.R.; Feldman, G.; Frey, S.E.; Galtier, F.; Hwang, S.J.; Innis, B.L.; Kovac, M.; Kremsner, P.; McNeil, S.; Nowakowski, A.; Richardus, J.H.; Trofa, A.; Oostvogels, L.; Verheugt, F.W.; et al.,

2013-01-01

BACKGROUND: We aimed to compare AS03-adjuvanted inactivated trivalent influenza vaccine (TIV) with non-adjuvanted TIV for seasonal influenza prevention in elderly people. METHODS: We did a randomised trial in 15 countries worldwide during the 2008-09 (year 1) and 2009-10 (year 2) influenza seasons.

Hypothesis driven development of new adjuvants: short peptides as immunomodulators.

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Dong, Jessica C; Kobinger, Gary P

2013-04-01

To date, vaccinations have been one of the key strategies in the prevention and protection against infectious pathogens. Traditional vaccines have well-known limitations such as safety and efficacy issues, which consequently deems it inappropriate for particular populations and may not be an effective strategy against all pathogens. This evidence highlights the need to develop more efficacious vaccination regiments. Higher levels of protection can be achieved by the addition of immunostimulating adjuvants. Many adjuvants elicit strong, undefined inflammation, which produces increased immunogenicity but may also lead to undesirable effects. Hypothesis driven development of adjuvants is needed to achieve a more specific and directed immune response required for optimal and safe vaccine-induced immune protection. An example of such hypothesis driven development includes the use of short immunomodulating peptides as adjuvants. These peptides have the ability to influence the immune response and can be extrapolated for adjuvant use, but requires further investigation.

Development of a minimal saponin vaccine adjuvant based on QS-21

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Fernández-Tejada, Alberto; Chea, Eric K.; George, Constantine; Pillarsetty, Nagavarakishore; Gardner, Jeffrey R.; Livingston, Philip O.; Ragupathi, Govind; Lewis, Jason S.; Tan, Derek S.; Gin, David Y.

2014-07-01

Adjuvants are materials added to vaccines to enhance the immunological response to an antigen. QS-21 is a natural product adjuvant under investigation in numerous vaccine clinical trials, but its use is constrained by scarcity, toxicity, instability and an enigmatic molecular mechanism of action. Herein we describe the development of a minimal QS-21 analogue that decouples adjuvant activity from toxicity and provides a powerful platform for mechanistic investigations. We found that the entire branched trisaccharide domain of QS-21 is dispensable for adjuvant activity and that the C4-aldehyde substituent, previously proposed to bind covalently to an unknown cellular target, is also not required. Biodistribution studies revealed that active adjuvants were retained preferentially at the injection site and the nearest draining lymph nodes compared with the attenuated variants. Overall, these studies have yielded critical insights into saponin structure-function relationships, provided practical synthetic access to non-toxic adjuvants, and established a platform for detailed mechanistic studies.

Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines

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Masayuki Hayashi

2017-02-01

Full Text Available Advax, a delta inulin-derived microparticle, has been developed as an adjuvant for several vaccines. However, its immunological characteristics and potential mechanism of action are yet to be elucidated. Here, we show that Advax behaves as a type-2 adjuvant when combined with influenza split vaccine, a T helper (Th2-type antigen, but behaves as a type-1 adjuvant when combined with influenza inactivated whole virion (WV, a Th1-type antigen. In addition, an adjuvant effect was not observed when Advax-adjuvanted WV vaccine was used to immunize toll-like receptor (TLR 7 knockout mice which are unable to respond to RNA contained in WV antigen. Similarly, no adjuvant effect was seen when Advax was combined with endotoxin-free ovalbumin, a neutral Th0-type antigen. An adjuvant effect was also not seen in tumor necrosis factor (TNF-α knockout mice, and the adjuvant effect required the presences of dendritic cells (DCs and phagocytic macrophages. Therefore, unlike other adjuvants, Advax potentiates the intrinsic or in-built adjuvant property of co-administered antigens. Hence, Advax is a unique class of adjuvant which can potentiate the intrinsic adjuvant feature of the vaccine antigens through a yet to be determined mechanism.

Who Benefits From Adjuvant Radiation Therapy for Gastric Cancer? A Meta-Analysis

International Nuclear Information System (INIS)

Ohri, Nitin; Garg, Madhur K.; Aparo, Santiago; Kaubisch, Andreas; Tome, Wolfgang; Kennedy, Timothy J.; Kalnicki, Shalom; Guha, Chandan

2013-01-01

Purpose: Large randomized trials have demonstrated significant survival benefits with the use of adjuvant chemotherapy or chemoradiation therapy for gastric cancer. The importance of adjuvant radiation therapy (RT) remains unclear. We performed an up-to-date meta-analysis of randomized trials testing the use of RT for resectable gastric cancer. Methods and Materials: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials testing adjuvant (including neoadjuvant) RT for resectable gastric cancer. Hazard ratios describing the impact of adjuvant RT on overall survival (OS) and disease-free survival (DFS) were extracted directly from the original studies or calculated from survival curves. Pooled estimates were obtained using the inverse variance method. Subgroup analyses were performed to determine whether the efficacy of RT varies with chemotherapy use, RT timing, geographic region, type of nodal dissection performed, or lymph node status. Results: Thirteen studies met all inclusion criteria and were used for this analysis. Adjuvant RT was associated with a significant improvement in both OS (HR = 0.78, 95% CI: 0.70-0.86, P<.001) and DFS (HR = 0.71, 95% CI: 0.63-0.80, P<.001). In the 5 studies that tested adjuvant chemoradiation therapy against adjuvant chemotherapy, similar effects were seen for OS (HR = 0.83, 95% CI: 0.67-1.03, P=.087) and DFS (HR = 0.77, 95% CI: 0.91-0.65, P=.002). Available data did not reveal any subgroup of patients that does not benefit from adjuvant RT. Conclusion: In randomized trials for resectable gastric cancer, adjuvant RT provides an approximately 20% improvement in both DFS and OS. Available data do not reveal a subgroup of patients that does not benefit from adjuvant RT. Further study is required to optimize the implementation of adjuvant RT for gastric cancer with regard to patient selection and integration with systemic therapy

Adjuvant Chemoradiation Therapy for Pancreatic Adenocarcinoma: Who Really Benefits?

Science.gov (United States)

Merchant, Nipun B; Rymer, Jennifer; Koehler, Elizabeth AS; Ayers, G Daniel; Castellanos, Jason; Kooby, David A; Weber, Sharon H; Cho, Clifford S; Schmidt, C Max; Nakeeb, Atilla; Matos, Jesus M; Scoggins, Charles R; Martin, Robert CG; Kim, Hong Jin; Ahmad, Syed A; Chu, Carrie K; McClaine, Rebecca; Bednarski, Brian K; Staley, Charles A; Sharp, Kenneth; Parikh, Alexander A

2014-01-01

BACKGROUND The role of adjuvant chemoradiation therapy (CRT) in pancreatic cancer remains controversial. The primary aim of this study was to determine if CRT improved survival in patients with resected pancreatic cancer in a large, multiinstitutional cohort of patients. STUDY DESIGN Patients undergoing resection for pancreatic adenocarcinoma from seven academic medical institutions were included. Exclusion criteria included patients with T4 or M1 disease, R2 resection margin, preoperative therapy, chemotherapy alone, or if adjuvant therapy status was unknown. RESULTS There were 747 patients included in the initial evaluation. Primary analysis was performed between patients that had surgery alone (n = 374) and those receiving adjuvant CRT (n = 299). Median followup time was 12.2 months and 14.5 months for survivors. Median overall survival for patients receiving adjuvant CRT was significantly longer than for those undergoing operation alone (20.0 months versus 14.5 months, p = 0.001). On subset and multivariate analysis, adjuvant CRT demonstrated a significant survival advantage only among patients who had lymph node (LN)-positive disease (hazard ratio 0.477, 95% CI 0.357 to 0.638) and not for LN-negative patients (hazard ratio 0.810, 95% CI 0.556 to 1.181). Disease-free survival in patients with LN-negative disease who received adjuvant CRT was significantly worse than in patients who had surgery alone (14.5 months versus 18.6 months, p = 0.034). CONCLUSIONS This large multiinstitutional study emphasizes the importance of analyzing subsets of patients with pancreas adenocarcinoma who have LN metastasis. Benefit of adjuvant CRT is seen only in patients with LN-positive disease, regardless of resection margin status. CRT in patients with LN-negative disease may contribute to reduced disease-free survival. PMID:19476845

Immune adjuvant activity of the olive, soybean and corn oils

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Ana Claudia Marinho da Silva

2016-08-01

Full Text Available In the last half of the century, a large amount of substances has been used as immune adjuvant. The immune adjuvant effect of olive, soybean and corn oils in Swiss mice immunized with ovalbumin (OVA plus aluminum hydroxide or emulsified in Marcol, soybean, olive or corn oils was evaluated through the OVA-specific antibodies determined by ELISA and Passive Cutaneous Anaphylaxis. In this work the comparison of the intensity of the immune response was established by the Bayesian analysis. The adjuvant effect of the vegetable oils was shown to be more effective than aluminium hydroxide. Regarding to OVA-specific IgE synthesis, olive oil had the slowest adjuvant effect of the three vegetable oils. Accordingly, olive oil was the most convenient among the vegetable oils to be used as immune adjuvant, since it stimulated a higher production of OVA-specific Ig and lower levels of anti-OVA IgE.

Learning impairment in honey bees caused by agricultural spray adjuvants.

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Timothy J Ciarlo

Full Text Available BACKGROUND: Spray adjuvants are often applied to crops in conjunction with agricultural pesticides in order to boost the efficacy of the active ingredient(s. The adjuvants themselves are largely assumed to be biologically inert and are therefore subject to minimal scrutiny and toxicological testing by regulatory agencies. Honey bees are exposed to a wide array of pesticides as they conduct normal foraging operations, meaning that they are likely exposed to spray adjuvants as well. It was previously unknown whether these agrochemicals have any deleterious effects on honey bee behavior. METHODOLOGY/PRINCIPAL FINDINGS: An improved, automated version of the proboscis extension reflex (PER assay with a high degree of trial-to-trial reproducibility was used to measure the olfactory learning ability of honey bees treated orally with sublethal doses of the most widely used spray adjuvants on almonds in the Central Valley of California. Three different adjuvant classes (nonionic surfactants, crop oil concentrates, and organosilicone surfactants were investigated in this study. Learning was impaired after ingestion of 20 µg organosilicone surfactant, indicating harmful effects on honey bees caused by agrochemicals previously believed to be innocuous. Organosilicones were more active than the nonionic adjuvants, while the crop oil concentrates were inactive. Ingestion was required for the tested adjuvant to have an effect on learning, as exposure via antennal contact only induced no level of impairment. CONCLUSIONS/SIGNIFICANCE: A decrease in percent conditioned response after ingestion of organosilicone surfactants has been demonstrated here for the first time. Olfactory learning is important for foraging honey bees because it allows them to exploit the most productive floral resources in an area at any given time. Impairment of this learning ability may have serious implications for foraging efficiency at the colony level, as well as potentially many

Adjuvant and Definitive Radiotherapy for Adrenocortical Carcinoma

International Nuclear Information System (INIS)

Sabolch, Aaron; Feng, Mary; Griffith, Kent; Hammer, Gary; Doherty, Gerard; Ben-Josef, Edgar

2011-01-01

Purpose: To evaluate the impact of both adjuvant and definitive radiotherapy on local control of adrenocortical carcinoma. Methods and Materials: Outcomes were analyzed from 58 patients with 64 instances of treatment for adrenocortical carcinoma at the University of Michigan's Multidisciplinary Adrenal Cancer Clinic. Thirty-seven of these instances were for primary disease, whereas the remaining 27 were for recurrent disease. Thirty-eight of the treatment regimens involved surgery alone, 10 surgery plus adjuvant radiotherapy, and 16 definitive radiotherapy for unresectable disease. The effects of patient, tumor, and treatment factors were modeled simultaneously using multiple variable Cox proportional hazards regression for associations with local recurrence, distant recurrence, and overall survival. Results: Local failure occurred in 16 of the 38 instances that involved surgery alone, in 2 of the 10 that consisted of surgery plus adjuvant radiotherapy, and in 1 instance of definitive radiotherapy. Lack of radiotherapy use was associated with 4.7 times the risk of local failure compared with treatment regimens that involved radiotherapy (95% confidence interval, 1.2-19.0; p = 0.030). Conclusions: Radiotherapy seems to significantly lower the risk of local recurrence/progression in patients with adrenocortical carcinoma. Adjuvant radiotherapy should be strongly considered after surgical resection.

Benefits of adjuvant chemotherapy in high-grade gliomas.

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DeAngelis, Lisa M

2003-12-01

The current standard of care for patients with high-grade glioma is resection followed by radiotherapy. Adjuvant chemotherapy is not widely accepted because of the low sensitivity of gliomas to traditional antineoplastic agents, the poor penetration of most drugs across the blood-brain barrier, and the significant systemic toxicity associated with current agents. However, nitrosoureas and, subsequently, temozolomide (Temodar [US], Temodal [international]; Schering-Plough Corporation, Kenilworth, NJ), a novel alkylating agent, cross the blood-brain barrier and have activity against gliomas. Nitrosoureas have been studied in phase III trials in the adjuvant setting. In individual trials, chemotherapy did not increase median survival but did increase the proportion of patients surviving >/=18 months by 15%. Only with large meta-analyses did the addition of chemotherapy achieve a statistically significant improvement in median survival. Currently there is no means of identifying which patients will benefit from adjuvant chemotherapy, but nitrosoureas and temozolomide are well tolerated in most patients, justifying the administration of adjuvant chemotherapy to all newly diagnosed patients with malignant glioma.

Adjuvanted vaccines: Aspects of immunosafety and modes of action

NARCIS (Netherlands)

Aalst, Susan van

2017-01-01

New developments in vaccine design shift towards safe, though sometimes less immunogenic, subunit and synthetic antigens. Therefore, the majority of current vaccines require adjuvants to increase immunogenicity. Most adjuvants available were developed empirically and their mode of action is only

Canadian Adjuvant Initiative Workshop, March 26–27, 2013—Ottawa, Canada

Science.gov (United States)

Krishnan, Lakshmi; Twine, Susan; Gerdts, Volker; Barreto, Luis; Richards, James C

2014-01-01

Novel adjuvants hold the promise for developing effective modern subunit vaccines capable of appropriately modulating the immune response against challenging diseases such as those caused by chronic and/or intracellular pathogens and cancer. Over the past decade there has been intensive research into discovering new adjuvants, however, their translation into routine clinical use is lagging. To stimulate discussion and identify opportunities for networking and collaboration among various stakeholders, a Canadian Adjuvant Initiative Workshop was held in Ottawa. Sponsored by the National Research Council Canada, Canadian Institutes of Health Research and the Vaccine Industry Committee, a two day workshop was held that brought together key Canadian and international stakeholders in adjuvant research from industry, academia and government. To discover innovation gaps and unmet needs, the presentations covered a board range of topics in adjuvant development; criteria for selection of lead adjuvant candidates from an industry perspective, discovery research across Canada, bioprocessing needs and challenges, veterinary vaccines, Canadian vaccine trial capabilities, the Canadian regulatory framework and WHO formulation laboratory experience. The workshop concluded with a discussion on the opportunity to create a Canadian Adjuvant Development Network. This report details the key discussion points and steps forward identified for facilitating adjuvant development research in Canada. PMID:24192752

Does brand differentiate pharmaceuticals?

Science.gov (United States)

Bednarik, Josef

2005-12-01

Role of marketing in pharmaceutical industry is increasing and inspiration by successful brands known from consumer goods market influenced pharmaceutical companies enough to switch their attention to branding initiatives. Still there is little evidence that pharmaceutical brands represent anything more than product only. This study aims to explore the area of branding in pharmaceutical industry. Central hypothesis of the research has been that brand and its emotional content differentiate pharmaceuticals as well as rational data derived from clinical studies. It has been tested by extensive review of available literature as well as by primary research focused on drivers of physicians' attitudes towards products and their influence on prescribing behavior. The research has been conducted in the sample of psychiatrists in the Czech Republic. No evidence about pharmaceutical brand exceeding value of product has been found in reviewed literature. Nevertheless, the primary research conducted in the sample of Czech psychiatrists indicates that emotional brand in pharmaceutical industry exists and enables author to draw a model of Customer/product life cycle that describes likely impact of functional, emotional and self-expressive benefits throughout pharmaceutical product's market presence. Pharmaceutical brand is likely to develop differently than the same of consumer goods products--it seems to be built predominantly on long-term positive experience. Marketing role in this process should lie in finding relevant product position and building brand identity compliant with real product capabilities.

Pharmaceutical manufacturing facility discharges can substantially increase the pharmaceutical load to U.S. wastewaters

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Scott, Tia-Marie; Phillips, Patrick J.; Kolpin, Dana W.; Colella, Kaitlyn M.; Furlong, Edward T.; Foreman, William T.; Gray, James L.

2018-01-01

Discharges from pharmaceutical manufacturing facilities (PMFs) previously have been identified as important sources of pharmaceuticals to the environment. Yet few studies are available to establish the influence of PMFs on the pharmaceutical source contribution to wastewater treatment plants (WWTPs) and waterways at the national scale. Consequently, a national network of 13 WWTPs receiving PMF discharges, six WWTPs with no PMF input, and one WWTP that transitioned through a PMF closure were selected from across the United States to assess the influence of PMF inputs on pharmaceutical loading to WWTPs. Effluent samples were analyzed for 120 pharmaceuticals and pharmaceutical degradates. Of these, 33 pharmaceuticals had concentrations substantially higher in PMF-influenced effluent (maximum 555,000 ng/L) compared to effluent from control sites (maximum 175 ng/L). Concentrations in WWTP receiving PMF input are variable, as discharges from PMFs are episodic, indicating that production activities can vary substantially over relatively short (several months) periods and have the potential to rapidly transition to other pharmaceutical products. Results show that PMFs are an important, national-scale source of pharmaceuticals to the environment.

Postoperative adjuvant therapy of colorectal carcinoma

International Nuclear Information System (INIS)

Scheithauer, W.

1989-01-01

Evaluating the results of controlled clinical trials, an attempt has been made to summarize the current status of adjuvant therapy in colorectal cancer. Several different adjuvant treatment approaches including immunotherapy, postoperative fibrinolysis, anticoagulation, pre- and postoperative radiotherapy when used as a single modality, have not resulted in any long-term survival benefit. Rather in contrast to previous experiences, recent prospective randomized trials have provided evidence for the efficacy of chemotherapy in the adjuvant treatment of colon and rectal cancer. Whereas its definitive role in the former disease remains somewhat controversial, for rectal cancer, it seems clear that combined modality therapy including polychemotherapy with or without radiation prolongs the disease-free interval, lowers the local recurrence rate, and may improve survival compared to surgery alone. Questions which remain to be answered by future clinical trials are related to the optimal duration and sequence of combined modality, to the role of different radiation sensitizers, and in both colon and rectal cancer, to the choice of the most effective systemtic chemotherapeutic drugs. (orig./MG) [de

Comparison of adjuvants for immune potentiating properties and side effects in mice

NARCIS (Netherlands)

Leenaars, P.P.A.M.; Hendriksen, C.F.M.; Koedam, M.A.; Claassen, I.; Claassen, E.

1995-01-01

Four types of adjuvants were evaluated as alternatives to the use of Freund's complete adjuvant in mice. The adjuvants evaluated included a water-in-oil emulsion (Specol), a microorganism (Lactobacillus), preformed immune-stimulating complexes (ISCOM) containing rabies virus glycoprotein and a

[Pharmaceutical logistic in turnover of pharmaceutical products of Azerbaijan].

Science.gov (United States)

Dzhalilova, K I

2009-11-01

Development of pharmaceutical logistic system model promotes optimal strategy for pharmaceutical functioning. The goal of such systems is organization of pharmaceutical product's turnover in required quantity and assortment, at preset time and place, at a highest possible degree of consumption readiness with minimal expenses and qualitative service. Organization of the optimal turnover chain in the region is offered to start from approximate classification of medicaments by logistic characteristics. Supplier selection was performed by evaluation of timeliness of delivery, quality of delivered products (according to the minimum acceptable level of quality) and time-keeping of time spending for orders delivery.

Adjuvant treatment and outcomes of stage III endometrial carcinoma

International Nuclear Information System (INIS)

Connell, C.; Ludbrook, J.; Davy, M.; Yeoh, E

2003-01-01

Surgery with staging using FIGO (1988) classification is accepted management for stage III endometrial carcinoma. The delivery of adjuvant therapy is controversial and tends to be individualised. Retrospective review of stage III endometrial carcinoma patients who underwent radical surgery at the Royal Adelaide and Queen Elizabeth Hospitals from 1984 to 2003 was carried out. Medical records were reviewed for details of patient characteristics, surgery, histopathology, adjuvant therapy and recurrence/survival. Sixty-six patients with a median age of 69 (37-97), had a median follow-up of 26 months (1-188 ). For all stage III patients, the actuarial 5-year disease-free and overall survivals were 50 and 43% respectively. Thirty-five patients received pelvic +/- paraaortic radiotherapy, 5 whole abdominal radiotherapy, 14 vaginal brachytherapy boost, 10 chemotherapy and 13 adjuvant hormones. Forty-six percent of patients recurred in a median time of 13 months (0-95). For these patients, the sites of first recurrence were pelvis in 27%, pelvis and abdomen in 23%, abdomen alone in 13%, distant alone in 27%, distant and abdominal in 7% and all three sites in 3%. On univariate analysis disease-free survival was impacted by; age, grade, parametrial involvement, number of extrauterine sites, lymphovascular invasion, adjuvant radiotherapy to the pelvis alone and postoperative macroscopic residual disease. Lymphovascular invasion, post-operative residual disease and adjuvant pelvic radiotherapy remained significant on multivariate analysis. These outcomes for stage III endometrial carcinoma are comparable to the current literature. Ongoing research is required to establish the most appropriate adjuvant therapy in these high risk patients

Cost-utility analysis of adjuvant goserelin (Zoladex and adjuvant chemotherapy in premenopausal women with breast cancer

Directory of Open Access Journals (Sweden)

Cheng Tsui

2012-01-01

Full Text Available Abstract Background Increased health care costs have made it incumbent on health-care facilities and physicians to demonstrate both clinical and cost efficacy when recommending treatments. Though studies have examined the cost-effectiveness of adjuvant goserelin with radiotherapy for locally advanced prostate cancer, few have compared the cost-effectiveness of adjuvant goserelin to adjuvant chemotherapy alone in premenopausal breast cancer. Methods In this retrospective study at one hospital, the records of 152 patients with stage Ia to IIIa ER + breast cancer who received goserelin or chemotherapy were reviewed. Survival analysis was assessed by the Kaplan-Meier method. Patients were interviewed to evaluate their quality of life using the European Organization for Research and Treatment Quality of Life questionnaire (EORTC-QLQ-C30, version 4.0, and to obtain the utility value by the standard gamble (SG and visual scale (VS methods. Total medical cost was assessed from the (National Health Insurance NHI payer's perspective. Results Survival at 11 years was significantly better in the groserelin group (P Conclusions Goserelin therapy results in better survival and higher utility-weighted life-years, and is more cost-effective than TC or TEC chemotherapy.

Adjuvant Treatment for Older Women with Invasive Breast Cancer

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Jolly, Trevor A; Williams, Grant R; Bushan, Sita; Pergolotti, Mackenzi; Nyrop, Kirsten A; Jones, Ellen L; Muss, Hyman B

2016-01-01

Older women experience a large share of breast cancer incidence and death. With the projected rise in the number of older cancer patients, adjuvant chemo-, radiation and endocrine therapy management will become a key component of breast cancer treatment in older women. Many factors influence adjuvant treatment decisions including patient preferences, life expectancy and tumor biology. Geriatric assessment predicts important outcomes, identifies key deficits, and can aid in the decision making process. This review utilizes clinical vignettes to illustrate core principles in adjuvant management of breast cancer in older women and suggests an approach incorporating life expectancy and geriatric assessment. PMID:26767315

Optimization of the pharmaceutical care system for diabetes patients using modern pharmaceutical informatics methodology

Directory of Open Access Journals (Sweden)

Андрій Ігорович Бойко

2016-04-01

Full Text Available Aim. Implementation of pharmaceutical informatics methods in the system of pharmaceutical care for diabetes patients in Ukraine.Methods. System method was used for the analysis of status and reforming the pharmaceutical care for patients with diabetes; program-oriented management at informatization project realization; pharmaceutical informatics in the creation of computer pharmaceutical knowledge bases; methods of data synthesis and summarizing.Results. System analysis of the basic directions of reforming the pharmaceutical care for patients with diabetes in Ukraine was carried out. Ways of it’s of optimization were processed: establishment of specialized pharmacies with implementation of modern information technologies and special postgraduate education for pharmacists. Structure and information providing of computer knowledge base “Pharmaceutical care for patients with diabetes” was substantiated.Conclusion. Based on the regional project “Informatization of prescription antidiabetic drugs circulation in Ukraine” realization, the necessity of establishment of specialized pharmacies providing pharmaceutical care for patients with diabetes was substantiated. Ways for optimization of postgraduate education for pharmacists of the specialized pharmacies by implementation of special thematic improvement cycles were proceed. Computer knowledge base as an effective tool for optimization of pharmaceutical care for patients with diabetes was realized

Adjuvants and delivery systems in veterinary vaccinology: current state and future developments

DEFF Research Database (Denmark)

Heegaard, Peter M. H.; Dedieu, Laurence; Johnson, Nicholas

2011-01-01

Modern adjuvants should induce strong and balanced immune responses, and it is often desirable to induce specific types of immunity. As an example, efficient Th1-immunity-inducing adjuvants are highly in demand. Such adjuvants promote good cell-mediated immunity against subunit vaccines that have...

Current adjuvant treatment modalities for gastric cancer: From history to the future

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Kilic, Leyla; Ordu, Cetin; Yildiz, Ibrahim; Sen, Fatma; Keskin, Serkan; Ciftci, Rumeysa; Pilanci, Kezban Nur

2016-01-01

The discrepancy between the surgical technique and the type of adjuvant chemotherapy used in clinical trials and patient outcomes in terms of overall survival rates has led to the generation of different adjuvant treatment protocols in distinct parts of the world. The adjuvant treatment recommendation is generally chemoradiotherapy in the United States, perioperative chemotherapy in the United Kingdom and parts of Europe, and chemotherapy in Asia. These options mainly rely on the United States Intergroup-0116, United Kingdom British Medical Research Council Adjuvant Gastric Infusional Chemotherapy, and the Asian Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer and Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer trials. However, the benefits were evident for only certain patients, which were not very homogeneous regarding the type of surgery, chemotherapy regimens, and stage of disease. Whether the dissimilarities in survival are attributable to surgical technique or intrinsic biological differences is a subject of debate. Regardless of the extent of surgery, multimodal therapy may offer modest survival advantage at least for diseases with lymph node involvement. Moreover, in the era of individualized treatment for most of the other cancer types, identification of special subgroups comprising those who will derive more or no benefit from adjuvant therapy merits further investigation. The aim of this review is to reveal the historical evolution and future reflections of adjuvant treatment modalities for resected gastric cancer patients. PMID:27190583

Does adjuvant therapy improve overall survival for stage IA/B pancreatic adenocarcinoma?

Science.gov (United States)

Ostapoff, Katherine T; Gabriel, Emmanuel; Attwood, Kristopher; Kuvshinoff, Boris W; Nurkin, Steven J; Hochwald, Steven N

2017-07-01

Current guidelines recommend adjuvant chemotherapy for resected pancreatic adenocarcinoma (PDAC). However, no studies have addressed its survival benefit for stage I patients as they comprise IA or IB PDAC were identified. Median OS was 60.3 months (mo) for stage IA and 36.9 mo for IB. 45.5% received adjuvant chemotherapy; 19.9% received adjuvant chemoradiation. There was OS benefit for both stage IA/IB patients with adjuvant chemotherapy (HR = 0.73 and 0.76 for IA and IB, respectively, p = 0.002 and IA disease (n = 1,477, 37.8%), age ≥70 (p < 0.001), higher grade (p < 0.001), ≤10 lymph nodes examined (p = 0.008), positive margins (p < 0.001), and receipt of adjuvant chemoradiation (p = 0.002) were associated with worse OS. For stage IB patients (n = 2,432, 62.2%), similar associations were observed with the exception of adjuvant chemoradiation whereby there was no significant association (p = 0.35). Adjuvant chemotherapy was associated with an OS benefit for patients with stage I PDAC; adjuvant chemoradiation was either of no benefit or associated with worse OS. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

THz spectroscopy: An emerging technology for pharmaceutical development and pharmaceutical Process Analytical Technology (PAT) applications

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Wu, Huiquan; Khan, Mansoor

2012-08-01

As an emerging technology, THz spectroscopy has gained increasing attention in the pharmaceutical area during the last decade. This attention is due to the fact that (1) it provides a promising alternative approach for in-depth understanding of both intermolecular interaction among pharmaceutical molecules and pharmaceutical product quality attributes; (2) it provides a promising alternative approach for enhanced process understanding of certain pharmaceutical manufacturing processes; and (3) the FDA pharmaceutical quality initiatives, most noticeably, the Process Analytical Technology (PAT) initiative. In this work, the current status and progress made so far on using THz spectroscopy for pharmaceutical development and pharmaceutical PAT applications are reviewed. In the spirit of demonstrating the utility of first principles modeling approach for addressing model validation challenge and reducing unnecessary model validation "burden" for facilitating THz pharmaceutical PAT applications, two scientific case studies based on published THz spectroscopy measurement results are created and discussed. Furthermore, other technical challenges and opportunities associated with adapting THz spectroscopy as a pharmaceutical PAT tool are highlighted.

Some Aspects Of Adjuvant Treatment Of Colorectal Cancer

International Nuclear Information System (INIS)

Hlavata, Z.

2008-01-01

Colorectal cancer is one of the most common cancers in Europe and in North America. Cornerstone of the treatment of localized colorectal cancer is surgical resection followed by chemotherapy or radio-chemotherapy in indicated cases. For patients with Stage III colon cancer recent data have shown efficacy through the combining fluorouracil-based chemotherapy with oxaliplatin into adjuvant treatment program. For patients with Stage II colon cancer, the use of adjuvant chemotherapy remains controversial, but may be appropriate in a subset of individuals at high risk for disease recurrence. Current randomized clinical trials in the adjuvant therapy of colorectal cancer are examining the value of adding agents known to be active in metastatic disease, including those that modify specific molecular targets. (author)

Old and new adjuvants for hepatitis B vaccines.

Science.gov (United States)

Leroux-Roels, Geert

2015-02-01

The safety and immunogenicity profiles of currently available recombinant hepatitis B vaccines are excellent. However, it remains a real challenge to induce protective immunity in the target groups that respond poorly or not at all to conventional vaccines. Ideally, a hepatitis B vaccine can be developed that conveys lifelong protection against infection rapidly after the injection of a single dose. Although this goal is far from being reached, important improvements have been made. Novel vaccine adjuvants have been developed that enhance the immunogenicity of recombinant hepatitis B vaccines while maintaining a good safety profile. The different adjuvants and adjuvant systems that are discussed herein have all been thoroughly evaluated in clinical trials and some have reached or are close to reach the market.

Clinical Practice of Adjuvant Chemotherapy in Patients with Early-Stage Epithelial Ovarian Cancer.

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Frielink, Lindy M J; Pijlman, Brenda M; Ezendam, Nicole P M; Pijnenborg, Johanna M A

2016-01-01

Adjuvant platinum-based chemotherapy improves survival in women with early-stage epithelial ovarian cancer (EOC). Yet, there is a wide variety in clinical practice. All patients diagnosed with FIGO I and IIa EOC (2006-2010) in the south of the Netherlands were analyzed. The percentage of patients that received adjuvant chemotherapy was determined as well as the comprehensiveness of staging and outcome. Forty percent (54/135) of the patients with early-stage EOC received adjuvant chemotherapy. Treatment with adjuvant chemotherapy was associated with FIGO stage, clear-cell histology and nonoptimal staging. Optimal staging was achieved in 50%, and nonoptimal staging was associated with advanced age, comorbidity and treatment in a non-referral hospital. Overall, there was no difference in outcome between patients with and without adjuvant chemotherapy. Yet, in grade 3 tumors, adjuvant chemotherapy seems beneficial. Selective treatment of patients with early-stage EOC might reduce adjuvant chemotherapy without compromising outcome. © 2016 S. Karger AG, Basel.

Postoperative adjuvant chemotherapy in rectal cancer operated for cure.

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Petersen, Sune Høirup; Harling, Henrik; Kirkeby, Lene Tschemerinsky; Wille-Jørgensen, Peer; Mocellin, Simone

2012-03-14

Colorectal cancer is one of the most common types of cancer in the Western world. Apart from surgery - which remains the mainstay of treatment for resectable primary tumours - postoperative (i.e., adjuvant) chemotherapy with 5-fluorouracil (5-FU) based regimens is now the standard treatment in Dukes' C (TNM stage III) colon tumours i.e. tumours with metastases in the regional lymph nodes but no distant metastases. In contrast, the evidence for recommendations of adjuvant therapy in rectal cancer is sparse. In Europe it is generally acknowledged that locally advanced rectal tumours receive preoperative (i.e., neoadjuvant) downstaging by radiotherapy (or chemoradiotion), whereas in the US postoperative chemoradiotion is considered the treatment of choice in all Dukes' C rectal cancers. Overall, no universal consensus exists on the adjuvant treatment of surgically resectable rectal carcinoma; moreover, no formal systematic review and meta-analysis has been so far performed on this subject. We undertook a systematic review of the scientific literature from 1975 until March 2011 in order to quantitatively summarize the available evidence regarding the impact of postoperative adjuvant chemotherapy on the survival of patients with surgically resectable rectal cancer. The outcomes of interest were overall survival (OS) and disease-free survival (DFS). CCCG standard search strategy in defined databases with the following supplementary search. 1. Rect* or colorect* - 2. Cancer or carcinom* or adenocarc* or neoplasm* or tumour - 3. Adjuv* - 4. Chemother* - 5. Postoper* Randomised controlled trials (RCT) comparing patients undergoing surgery for rectal cancer who received no adjuvant chemotherapy with those receiving any postoperative chemotherapy regimen. Two authors extracted data and a third author performed an independent search for verification. The main outcome measure was the hazard ratio (HR) between the risk of event between the treatment arm (adjuvant chemotherapy

Pharmaceutical formulations as immunological adjuvants

Energy Technology Data Exchange (ETDEWEB)

O' Hagan, D T

1987-01-01

The aim of this work was to enhance the immune responses to ovalbumin (OVA) following its oral administration, by the association of the protein with colloidal carriers, which may protect the protein from degradation in the gastrointestinal tract and/or facilitate its uptake across the intestine. An enzyme linked immunosorbent assay (ELISA) was established for the determination of rat anti-OVA antibodies and an immunization protocol was established to induce a statistically significant salivary antibody response to OVA in the rat. A radioimmunoassay for the determination of rat anti-OVA antibodies was also established, to confirm the ELISA results. Methods were established to determine the extent of incorporation or adsorption of OVA into or onto the colloidal carrier formations.

Evaluation of P-Listed Pharmaceutical Residues in Empty Pharmaceutical Containers

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Under the Resource Conservation and Recovery Act (RCRA), some pharmaceuticals are considered acute hazardous wastes because their sole active pharmaceutical ingredients are P-listed commercial chemical products (40 CFR 261.33). Hospitals and other healthcare facilities have stru...

Use of chemical and biological adjuvants to achieve the optimum application of radiological techniques

International Nuclear Information System (INIS)

Azab, K.S.

2010-01-01

Nowadays, the optimization and attainment of maximum guarantee are representing the real challenge for the nuclear technology exercise. The Adjuvant techniques might be considered one of the available tactics for the developing, reducing risk and facilitating secure clearing of nuclear waste in the field of radiation technology applications. The history describes the belief that an adjuvant is required for immunity because the immune system evolved to respond to dangerous situations such as infections, and the presence of an adjuvant is the mechanism used to identify these situations. In immunology, an adjuvant is an agent that may stimulate the immune system and increase the response to a vaccine, without having any specific antigenic effect. Adjuvants are coming increasingly into focus for vaccine developers since many novel split and subunit vaccines are insufficiently immunogenic on their own. Among the used today are alum (aluminum hydroxide) and Glycosyl ceramides. It is worth mentioning that manufacturers already had produced thousands of different adjuvants, for both industrial and agricultural purposes. Today, the agricultural and horticultural industries are being overwhelmed by adjuvant choices. Complete Freunds adjuvant is the adjuvant used in animal research studies of basic and applied immunology. (author)

Self-Adjuvanting Glycopeptide Conjugate Vaccine against Disseminated Candidiasis

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Xin, Hong; Cartmell, Jonathan; Bailey, Justin J.; Dziadek, Sebastian; Bundle, David R.; Cutler, Jim E.

2012-01-01

Our research on pathogenesis of disseminated candidiasis led to the discovery that antibodies specific for Candida albicans cell surface β-1, 2–mannotriose [β-(Man)3] protect mice. A 14 mer peptide Fba, which derived from the N-terminal portion of the C. albicans cytosolic/cell surface protein fructose-bisphosphate aldolase, was used as the glycan carrier and resulted in a novel synthetic glycopeptide vaccine β-(Man)3-Fba. By a dendritic cell-based immunization approach, this conjugate induced protective antibody responses against both the glycan and peptide parts of the vaccine. In this report, we modified the β-(Man)3-Fba conjugate by coupling it to tetanus toxoid (TT) in order to improve immunogenicity and allow for use of an adjuvant suitable for human use. By new immunization procedures entirely compatible with human use, the modified β-(Man)3-Fba-TT was administered either alone or as a mixture made with alum or monophosphoryl lipid A (MPL) adjuvants and given to mice by a subcutaneous (s.c.) route. Mice vaccinated with or, surprisingly, without adjuvant responded well by making robust antibody responses. The immunized groups showed a high degree of protection against a lethal challenge with C. albicans as evidenced by increased survival times and reduced kidney fungal burden as compared to control groups that received only adjuvant or DPBS buffer prior to challenge. To confirm that induced antibodies were protective, sera from mice immunized against the β-(Man)3-Fba-TT conjugate transferred protection against disseminated candidiasis to naïve mice, whereas C. albicans-absorbed immune sera did not. Similar antibody responses and protection induced by the β-(Man)3-Fba-TT vaccine was observed in inbred BALB/c and outbred Swiss Webster mice. We conclude that addition of TT to the glycopeptide conjugate results in a self-adjuvanting vaccine that promotes robust antibody responses without the need for additional adjuvant, which is novel and represents a

Protein antigen adsorption to the DDA/TDB liposomal adjuvant

DEFF Research Database (Denmark)

Hamborg, Mette; Jorgensen, Lene; Bojsen, Anders Riber

2013-01-01

Understanding the nature of adjuvant-antigen interactions is important for the future design of efficient and safe subunit vaccines, but remains an analytical challenge. We studied the interactions between three model protein antigens and the clinically tested cationic liposomal adjuvant composed...... of dimethyldioctadecylammonium (DDA) and trehalose 6,6'-dibehenate (TDB)....

Activity of glycated chitosan and other adjuvants to PDT vaccines

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Korbelik, Mladen; Banáth, Judit; Čiplys, Evaldas; Szulc, Zdzislaw; Bielawska, Alicja; Chen, Wei R.

2015-03-01

Glycated chitosan (GC), a water soluble galactose-conjugated natural polysaccharide, has proven to be an effective immunoadjuvant for treatment of tumors based on laser thermal therapy. It was also shown to act as adjuvant for tumor therapy with high-intensity ultrasound and in situ photodynamic therapy (PDT). In the present study, GC was examined as potential adjuvant to PDT-generated cancer vaccine. Two other agents, pure calreticulin protein and acid ceramidase inhibitor LCL521, were also tested as prospective adjuvants for use in conjunction with PDT vaccines. Single treatment with GC, included with PDT vaccine cells suspension, improved the therapeutic efficacy when compared to vaccine alone. This attractive prospect of GC application remains to be carefully optimized and mechanistically elucidated. Both calreticulin and LCL521 proved also effective adjuvants when combined with PDT vaccine tumor treatment.

A systematic review and meta-analysis on the safety of newly adjuvanted vaccines among children.

Science.gov (United States)

Stassijns, Jorgen; Bollaerts, Kaatje; Baay, Marc; Verstraeten, Thomas

2016-02-03

New adjuvants such as the AS- or the MF59-adjuvants improve vaccine efficacy and facilitate dose-sparing. Their use in influenza and malaria vaccines has resulted in a large body of evidence on their clinical safety in children. We carried out a systematic search for safety data from published clinical trials on newly adjuvanted vaccines in children ≤10 years of age. Serious adverse events (SAEs), solicited AEs, unsolicited AEs and AEs of special interest were evaluated for four new adjuvants: the immuno-stimulants containing adjuvant systems AS01 and AS02, and the squalene containing oil-in-water emulsions AS03 and MF59. Relative risks (RR) were calculated, comparing children receiving newly adjuvanted vaccines to children receiving other vaccines with a variety of antigens, both adjuvanted and unadjuvanted. Twenty-nine trials were included in the meta-analysis, encompassing 25,056 children who received at least one dose of the newly adjuvanted vaccines. SAEs did not occur more frequently in adjuvanted groups (RR 0.85, 95%CI 0.75-0.96). Our meta-analyses showed higher reactogenicity following administration of newly adjuvanted vaccines, however, no consistent pattern of solicited AEs was observed across adjuvant systems. Pain was the most prevalent AE, but often mild and of short duration. No increased risks were found for unsolicited AEs, febrile convulsions, potential immune mediated diseases and new onset of chronic diseases. Our meta-analysis did not show any safety concerns in clinical trials of the newly adjuvanted vaccines in children ≤10 years of age. An unexplained increase of meningitis in one Phase III AS01-adjuvanted malaria trial and the link between narcolepsy and the AS03-adjuvanted pandemic vaccine illustrate that continued safety monitoring is warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

The effect of several adjuvants on glufosinate effectiveness in Conyza species.

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Fernandez-Cerejido, M C; Bastida, F; Menendez, J

2009-01-01

The effect of several adjuvants on the effectiveness of glufosinate and the role of adherence and contact angle modifications due to the presence of these adjuvants in the spraying solution on the increase in efficacy observed on the broadleaved weeds Conyza albida and Conyza bonariensis has been determined under laboratory controlled conditions. The adjuvants used on the experiment were a mixture of methyl oleate and palmitate (MO/MP), a dodecylbenzene ammonium sulphonate (DBAS), a paraffinic oil (PO), an alkylglycol ester (AGE), and a lecithin + propionic acid + non ionic surfactant based product (LI-700). Dose-response experiments showed that C. albida displayed higher susceptibility to glufosinate than C. bonariensis, no matter the adjuvant tested. However, none of the mixtures increased the herbicide effectiveness on C. atlbida, with LI 700 and PO showing an antagonistic effect on the herbicide efficacy. On C. bonariensis, MO/MP and DBAS showed significant better results than non-amended glufosinate controls, with LI 700 showing again an antagonistic effect. Both adherence and contact angle studies were inconclusive, since adjuvants with best adherence and contact angle values were not the most effective ones. Therefore, other unknown parameters putatively modified by adjuvants such as herbicide penetration should be questioned.

Trastuzumab-associated cardiac adverse effects in the herceptin adjuvant trial

NARCIS (Netherlands)

Suter, Thomas M.; Procter, Marion; van Veldhuisen, Dirk J.; Muscholl, Michael; Bergh, Jonas; Carlomagno, Chiara; Perren, Timothy; Passalacqua, Rodolfo; Bighin, Claudia; Klijn, Jan G. M.; Ageev, Fail T.; Hitre, Erika; Groetz, Juergen; Iwata, Hiroji; Knap, Malgorzata; Gnant, Michael; Muehlbauer, Susanne; Spence, Alison; Gelber, Richard D.; Piccart-Gebhart, Martine J.

2007-01-01

Purpose The purpose of this analysis was to investigate trastuzumab- associated cardiac adverse effects in breast cancer patients after completion of ( neo) adjuvant chemotherapy with or without radiotherapy. Patients and Methods The Herceptin Adjuvant ( HERA) trial is a three- group, multicenter,

Physician Beliefs and Practices for Adjuvant and Salvage Radiation Therapy After Prostatectomy

International Nuclear Information System (INIS)

Showalter, Timothy N.; Ohri, Nitin; Teti, Kristopher G.; Foley, Kathleen A.; Keith, Scott W.; Trabulsi, Edouard J.; Lallas, Costas D.; Dicker, Adam P.; Hoffman-Censits, Jean; Pizzi, Laura T.; Gomella, Leonard G.

2012-01-01

Purpose: Despite results of randomized trials that support adjuvant radiation therapy (RT) after radical prostatectomy (RP) for prostate cancer with adverse pathologic features (APF), many clinicians favor selective use of salvage RT. This survey was conducted to evaluate the beliefs and practices of radiation oncologists (RO) and urologists (U) regarding RT after RP. Methods and Materials: We designed a Web-based survey of post-RP RT beliefs and policies. Survey invitations were e-mailed to a list of 926 RO and 591 U. APF were defined as extracapsular extension, seminal vesicle invasion, or positive surgical margin. Differences between U and RO in adjuvant RT recommendations were evaluated by comparative statistics. Multivariate analyses were performed to evaluate factors predictive of adjuvant RT recommendation. Results: Analyzable surveys were completed by 218 RO and 92 U (overallresponse rate, 20%). Adjuvant RT was recommended based on APF by 68% of respondents (78% RO, 44% U, p <0.001). U were less likely than RO to agree that adjuvant RT improves survival and/or biochemical control (p < 0.0001). PSA thresholds for salvage RT were higher among U than RO (p < 0.001). Predicted rates of erectile dysfunction due to RT were higher among U than RO (p <0.001). On multivariate analysis, respondent specialty was the only predictor of adjuvant RT recommendations. Conclusions: U are less likely than RO to recommend adjuvant RT. Future research efforts should focus on defining the toxicities of post-RP RT and on identifying the subgroups of patients who will benefit from adjuvant vs. selective salvage RT.

Physician Beliefs and Practices for Adjuvant and Salvage Radiation Therapy After Prostatectomy

Energy Technology Data Exchange (ETDEWEB)

Showalter, Timothy N., E-mail: timothy.showalter@jeffersonhospital.org [Department of Radiation Oncology, Jefferson Medical College, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Ohri, Nitin; Teti, Kristopher G. [Department of Radiation Oncology, Jefferson Medical College, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Foley, Kathleen A. [Strategic Consulting, Thomson Reuters Healthcare, Cambridge, MA (United States); Keith, Scott W. [Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Trabulsi, Edouard J.; Lallas, Costas D. [Department of Urology, Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Dicker, Adam P. [Department of Radiation Oncology, Jefferson Medical College, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Hoffman-Censits, Jean [Department of Medical Oncology, Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Pizzi, Laura T. [School of Pharmacy, Thomas Jefferson University, Philadelphia, PA (United States); Gomella, Leonard G. [Department of Urology, Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States)

2012-02-01

Purpose: Despite results of randomized trials that support adjuvant radiation therapy (RT) after radical prostatectomy (RP) for prostate cancer with adverse pathologic features (APF), many clinicians favor selective use of salvage RT. This survey was conducted to evaluate the beliefs and practices of radiation oncologists (RO) and urologists (U) regarding RT after RP. Methods and Materials: We designed a Web-based survey of post-RP RT beliefs and policies. Survey invitations were e-mailed to a list of 926 RO and 591 U. APF were defined as extracapsular extension, seminal vesicle invasion, or positive surgical margin. Differences between U and RO in adjuvant RT recommendations were evaluated by comparative statistics. Multivariate analyses were performed to evaluate factors predictive of adjuvant RT recommendation. Results: Analyzable surveys were completed by 218 RO and 92 U (overallresponse rate, 20%). Adjuvant RT was recommended based on APF by 68% of respondents (78% RO, 44% U, p <0.001). U were less likely than RO to agree that adjuvant RT improves survival and/or biochemical control (p < 0.0001). PSA thresholds for salvage RT were higher among U than RO (p < 0.001). Predicted rates of erectile dysfunction due to RT were higher among U than RO (p <0.001). On multivariate analysis, respondent specialty was the only predictor of adjuvant RT recommendations. Conclusions: U are less likely than RO to recommend adjuvant RT. Future research efforts should focus on defining the toxicities of post-RP RT and on identifying the subgroups of patients who will benefit from adjuvant vs. selective salvage RT.

Cognitive function after adjuvant treatment for early breast cancer

DEFF Research Database (Denmark)

Debess, Jeanne; Riis, Jens Østergaard; Engebjerg, Malene Cramer

2010-01-01

The purpose of this study was to examine cognitive function in patients with early breast cancer before and after adjuvant chemotherapy or 6 months of tamoxifen. We performed a population-based study in the county of North Jutland, Denmark, including 120 women aged ... chemotherapy with seven cycles of cyclophosphamide, epirubicin and fluoruracil or adjuvant tamoxifen for 6 months for early breast cancer from 2004 to 2006. They were compared with an aged-matched group of 208 women without previous cancer selected randomly from the same population. Data were collected before...... themselves as impaired at 6 months. Our results do not support that adjuvant chemotherapy is associated with cognitive side effects in breast cancer patients....

The argument for pharmaceutical policy.

Science.gov (United States)

Traulsen, Janine Morgall; Almarsdóttir, Anna Birna

2005-02-01

Pharmaceutical policy is a global concern. It has become a hot political topic in most countries--developed as well as developing--and can be found on the agenda of international organizations such as WHO, OECD, EU, WTO and even the World Bank. Pharmaceutical policy affects everyone in the world of pharmacy and it is therefore imperative that it be understood, discussed and debated within the pharmacy profession and included in the curriculum of schools of pharmacy. This, the first article in a series, argues for the importance of the academic discipline of pharmaceutical policy analysis and the involvement of pharmacists in this endeavour. The aim of the authors is to stimulate an informed and critical appreciation of this field. The authors begin with an introduction to the field of pharmaceutical policy, introducing several important concepts and current trends including: medicines regulation; how pharmaceutical policy is made; pharmaceutical policy as a dynamic process; and the new public health as a global issue. The article ends with a short description of the remaining five articles in the series which will deal with important aspects of pharmaceutical policy. The topics include: economic pressures on health care systems; drug utilization from the clinical viewpoint (rational use of medicines); the impact of pharmaceutical policy on patients and the patient impact on pharmaceutical policy; the professional perspective; and finally the last article which deals with studying and evaluating pharmaceutical policy.

Factors Affecting Adjuvant Therapy in Stage III Pancreatic Cancer—Analysis of the National Cancer Database

Directory of Open Access Journals (Sweden)

Mridula Krishnan

2017-08-01

Full Text Available Background: Adjuvant therapy after curative resection is associated with survival benefit in stage III pancreatic cancer. We analyzed the factors affecting the outcome of adjuvant therapy in stage III pancreatic cancer and compared overall survival with different modalities of adjuvant treatment. Methods: This is a retrospective study of patients with stage III pancreatic cancer listed in the National Cancer Database (NCDB who were diagnosed between 2004 and 2012. Patients were stratified based on adjuvant therapy they received. Unadjusted Kaplan-Meier and multivariable Cox regression analysis were performed. Results: We analyzed a cohort included 1731 patients who were recipients of adjuvant therapy for stage III pancreatic cancer within the limits of our database. Patients who received adjuvant chemoradiation had the longest postdiagnosis survival time, followed by patients who received adjuvant chemotherapy, and finally patients who received no adjuvant therapy. On multivariate analysis, advancing age and patients with Medicaid had worse survival, whereas Spanish origin and lower Charlson comorbidity score had better survival. Conclusions: Our study is the largest trial using the NCDB addressing the effects of adjuvant therapy specifically in stage III pancreatic cancer. Within the limits of our study, survival benefit with adjuvant therapy was more apparent with longer duration from date of diagnosis.

Exploring patient experiences of neo-adjuvant chemotherapy for breast cancer.

Science.gov (United States)

Beaver, Kinta; Williamson, Susan; Briggs, Jean

2016-02-01

Neo-adjuvant chemotherapy is recommended for 'inoperable' locally advanced and inflammatory breast cancers. For operable breast cancers, trials indicate no survival differences between chemotherapy given pre or post-surgery. Communicating evidence based information to patients is complex and studies examining patient experiences of neo-adjuvant chemotherapy are lacking. This study aims to explore the experiences of women who received neo-adjuvant chemotherapy for breast cancer. A qualitative approach using in-depth interviews with 20 women who had completed neo-adjuvant chemotherapy for breast cancer. Interview data were analysed using thematic analysis. The sample included a relatively young group of women, with caring responsibilities. Five main themes emerged: coping with the rapid transition from 'well' to 'ill', information needs and decision making, needing support and empathy, impact on family, and creating a new 'normal'. More support was needed towards the end of chemotherapy, when side effects were at their most toxic, and decisions about forthcoming surgery were being made. Some women were referred to psychological services, but usually when a crisis point had been reached. Information and support would have been beneficial at key time points. This information is vital in developing services and interventions to meet the complex needs of these patients and potentially prevent late referral to psychological services. Specialist oncology nurses are able to develop empathetic relationships with patients and have the experience, knowledge and skills to inform and support women experiencing neo-adjuvant chemotherapy. Targeting key time points and maintaining relationship throughout neo-adjuvant chemotherapy would be highly beneficial. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Logistics in the pharmaceutical service].

Science.gov (United States)

Stanko, P; Fulmeková, M

2005-11-01

The conception of the field of pharmaceutical service defines pharmaceutical service as the basic part of pharmacy, the principal task of which is to provide pharmaceutical care as an inseparable part of providing health care. It represents a set of professional activities of the pharmacist oriented to securing human and veterinary pharmaceutical products and health care products and to optimising effective, safe and quality pharmacotherapy. Technically, pharmaceutical service is an applied discipline, as it makes use of knowledge gained in other pharmaceutical, medical, psychological, social, and economic sciences. Because of its interdisciplinary character it is necessary to extend the theory of pharmaceutical service in such a way so that it may reflect all aspects of its sphere of activity. One of the possibilities is to define the pharmacy premises as an independent functional unit which operates on the basis of valid legal standards in such a way that on the one hand it secures the provision of health (pharmaceutical) care, and on the other hand it maintains its cost-effectiveness. To keep the quality of care of the patient and the economic aspect in balance, it is necessary to define the term pharmaceutical logistics also under the conditions of Slovak (Czech) pharmacy as early satisfaction of the requirements of the patient (client) in the pharmacy premises, which means that the appropriate pharmaceutical product or health care product and the appropriate information must be at the right time in the required amount and required quality in the right place.

Adjuvant Therapy for Stage II Colorectal Cancer: Who and with What?

Science.gov (United States)

Chung, Ki-Young Y; Kelsen, David

2006-06-01

The role of adjuvant chemotherapy for patients with stage II colon adenocarcinoma remains controversial. The high surgical cure rate for patients with "low-risk" stage II colon cancer, ranging from 75% to 80%, and the available clinical trials and meta-analyses provide conflicting recommendations for or against adjuvant chemotherapy for this group of patients. For fit "high-risk" stage II patients with clinical obstruction or perforation at presentation, in which the 5-year survival rate is 60% to 70%, there is little controversy, as these patients are routinely treated with adjuvant chemotherapy. Other potential high-risk factors, including high histologic grade, microsatellite instability, and loss of 18q, have yet to be validated in prospective trials. Patients with fewer than 12 regional lymph nodes identified in the surgical specimen have a statistically unclear risk of lymph node involvement. These patients may have stage III disease and should receive adjuvant therapy. The decision to use adjuvant chemotherapy to treat low-risk stage II colon cancer patients (no obstruction or perforation) should be an informed decision weighing the magnitude of a net 2% to 5% survival benefit, a 0.5% to 1.0% risk of mortality with chemotherapy in addition to 6 months of chemotherapy-related toxicities, other coexisting patient morbidities, and the anticipated life expectancy of each patient. As adjuvant chemotherapy is therapy addressing local or metastatic microscopic disease, and the effectiveness of systemic and biologically targeted therapy for advanced macroscopic colon cancer continues to improve rapidly, it remains to be determined by clinical trials whether therapies including newer agents such as cetuximab and bevacizumab administered in the adjuvant setting may affect survival for stage II cancer patients.

Adjuvant whole brain radiotherapy: strong emotions decide but rational studies are needed.

Science.gov (United States)

Brown, Paul D; Asher, Anthony L; Farace, Elana

2008-04-01

Brain metastases are common in cancer patients and cause considerable morbidity and mortality. For patients with limited disease and good performance status, treatment typically involves a combination of focal measures (e.g., surgical resection or radiosurgery) for the radiographically apparent disease, followed by adjuvant whole brain radiotherapy (WBRT) to treat subclinical disease. Because of concerns regarding the toxicity of WBRT, especially neurocognitive deterioration, many have advocated withholding adjuvant WBRT. Recently published studies have shed more light on the efficacy of adjuvant WBRT and the neurocognitive effects of WBRT. However, the inclusion of neurocognitive and quality-of-life data in clinical trials are still required to better define the role of adjuvant WBRT. Currently, two Phase III trials are underway, one in Europe and one in North America, that will determine the effect of adjuvant WBRT on patients' quality of life, neurocognitive function, and survival.

Adjuvant Whole Brain Radiotherapy: Strong Emotions Decide But Rational Studies Are Needed

Energy Technology Data Exchange (ETDEWEB)

Brown, Paul D. [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States)], E-mail: brown.paul@mayo.edu; Asher, Anthony L [Brain and Spinal Cord Tumors Programs, Carolinas Medical Center and Presbyterian Hospital, Charlotte, NC (United States); Farace, Elana [Department of Neurosurgery, Pennsylvania State University, Penn State Milton S. Hershey Medical Center, Hershey, PA (United States)

2008-04-01

Brain metastases are common in cancer patients and cause considerable morbidity and mortality. For patients with limited disease and good performance status, treatment typically involves a combination of focal measures (e.g., surgical resection or radiosurgery) for the radiographically apparent disease, followed by adjuvant whole brain radiotherapy (WBRT) to treat subclinical disease. Because of concerns regarding the toxicity of WBRT, especially neurocognitive deterioration, many have advocated withholding adjuvant WBRT. Recently published studies have shed more light on the efficacy of adjuvant WBRT and the neurocognitive effects of WBRT. However, the inclusion of neurocognitive and quality-of-life data in clinical trials are still required to better define the role of adjuvant WBRT. Currently, two Phase III trials are underway, one in Europe and one in North America, that will determine the effect of adjuvant WBRT on patients' quality of life, neurocognitive function, and survival.

Adjuvant Whole Brain Radiotherapy: Strong Emotions Decide But Rational Studies Are Needed

International Nuclear Information System (INIS)

Brown, Paul D.; Asher, Anthony L.; Farace, Elana

2008-01-01

Brain metastases are common in cancer patients and cause considerable morbidity and mortality. For patients with limited disease and good performance status, treatment typically involves a combination of focal measures (e.g., surgical resection or radiosurgery) for the radiographically apparent disease, followed by adjuvant whole brain radiotherapy (WBRT) to treat subclinical disease. Because of concerns regarding the toxicity of WBRT, especially neurocognitive deterioration, many have advocated withholding adjuvant WBRT. Recently published studies have shed more light on the efficacy of adjuvant WBRT and the neurocognitive effects of WBRT. However, the inclusion of neurocognitive and quality-of-life data in clinical trials are still required to better define the role of adjuvant WBRT. Currently, two Phase III trials are underway, one in Europe and one in North America, that will determine the effect of adjuvant WBRT on patients' quality of life, neurocognitive function, and survival

Engineering of an Inhalable DDA/TDB Liposomal Adjuvant

DEFF Research Database (Denmark)

Ingvarsson, Pall Thor; Yang, Mingshi; Mulvad, Helle

2013-01-01

The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB).......The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB)....

Pharmaceutical powder compaction technology

National Research Council Canada - National Science Library

Çelik, Metin

2011-01-01

"Revised to reflect modern pharmaceutical compacting techniques, this Second Edition guides pharmaceutical engineers, formulation scientists, and product development and quality assurance personnel...

Aluminium based adjuvants and their effects on mitochondria and lysosomes of phagocytosing cells.

Science.gov (United States)

Ohlsson, Lars; Exley, Christopher; Darabi, Anna; Sandén, Emma; Siesjö, Peter; Eriksson, Håkan

2013-11-01

Aluminium oxyhydroxide, Al(OH)3 is one of few compounds approved as an adjuvant in human vaccines. However, the mechanism behind its immune stimulating properties is still poorly understood. In vitro co-culture of an aluminium adjuvant and the human monocytic cell line THP-1 resulted in reduced cell proliferation. Inhibition occurred at concentrations of adjuvant several times lower than would be found at the injection site using a vaccine formulation containing an aluminium adjuvant. Based on evaluation of the mitochondrial membrane potential, THP-1 cells showed no mitochondrial rupture after co-culture with the aluminium adjuvant, instead an increase in mitochondrial activity was seen. The THP-1 cells are phagocytosing cells and after co-culture with the aluminium adjuvant the phagosomal pathway was obstructed. Primary or early phagosomes mature into phagolysosomes with an internal pH of 4.5 - 5 and carry a wide variety of hydrolysing enzymes. Co-culture with the aluminium adjuvant yielded a reduced level of acidic vesicles and cathepsin L activity, a proteolytic enzyme of the phagolysosomes, was almost completely inhibited. THP-1 cells are an appropriate in vitro model in order to investigate the mechanism behind the induction of a phagocytosing antigen presenting cell into an inflammatory cell by aluminium adjuvants. Much information will be gained by investigating the phagosomal pathway and what occurs inside the phagosomes and to elucidate the ultimate fate of phagocytosed aluminium particles. © 2013.

Pharmaceutical advertising in emergency departments.

Science.gov (United States)

Marco, Catherine A

2004-04-01

Promotion of prescription drugs represents a growing source of pharmaceutical marketing expenditures. This study was undertaken to identify the frequency of items containing pharmaceutical advertising in clinical emergency departments (EDs). In this observational study, emergency physician on-site investigators quantified a variety of items containing pharmaceutical advertising present at specified representative times and days, in clinical EDs. Measurements were obtained by 65 on-site investigators, representing 22 states. Most EDs in this study were community EDs (87% community and 14% university or university affiliate), and most were in urban settings (50% urban, 38% suburban, and 13% rural). Investigators measured 42 items per ED (mean = 42; median = 31; interquartile range of 14-55) containing pharmaceutical advertising in the clinical area. The most commonly observed items included pens (mean 15 per ED; median 10), product brochures (mean 5; median 3), stethoscope labels (mean 4; median 2), drug samples (mean 3; median 0), books (mean 3.4), mugs (mean 2.4), and published literature (mean 3.1). EDs with a policy restricting pharmaceutical representatives in the ED had significantly fewer items containing pharmaceutical advertising (median 7.5; 95% CI = 0 to 27) than EDs without such a policy (median 35; 95% CI = 27 to 47, p = 0.005, nonparametric Wilcoxon two-sample test). There were no differences in quantities of pharmaceutical advertising for EDs in community compared with university settings (p = 0.5), rural compared with urban settings (p = 0.3), or annual ED volumes (p = 0.9). Numerous items containing pharmaceutical advertising are frequently observed in EDs. Policies restricting pharmaceutical representatives in the ED are associated with reduced pharmaceutical advertising.

Physical exercise during adjuvant chemotherapy

NARCIS (Netherlands)

van Waart, H.

2017-01-01

This thesis evaluates the effect of physical exercise during chemotherapy. In chapter two the study design, rationale and methods of the Physical exercise during Adjuvant Chemotherapy Study (PACES) are described. Chapter three presents the effects of the randomized controlled trial evaluating a

Tropical Journal of Pharmaceutical Research

African Journals Online (AJOL)

Journal Homepage Image. We seek to encourage pharmaceutical and allied research of tropical and international relevance and to foster multidisciplinary research and collaboration among scientists, the pharmaceutical industry and the healthcare professionals. We publish articles in pharmaceutical sciences and related ...

The Korean Pharmaceutical Industry and the Expansion of the General Pharmaceuticals Market in the 1950-1960s

Directory of Open Access Journals (Sweden)

Kyu-Hwan SIHN

2015-12-01

Full Text Available After the Liberation, the Korean economy was dependent on relief supplies and aid after the ruin of the colonial regime and war. The pharmaceutical business also searched for their share in the delivery of military supplies and the distribution of relief supplies. The supply-side pharmaceutical policy made the pharmaceutical market a wholesale business. The gravity of the situation led to an increased importation of medical supplies, and wholesalers took the lead in establishing the distribution structure, whereas consumers and pharmaceutical business were relatively intimidated. The aid provided by the International Cooperation Administration (ICA marked a turning point in the Korean pharmaceutical industry after the middle of the 1950s. ICA supplied raw materials and equipment funds, while the pharmaceutical business imported advanced technology and capital. The government invited the local production of medical substances, whereas pharmaceutical businesses replaced imported medical substances with locally produced antibiotics. After the 1960s, the production of antibiotics reached saturation. Pharmaceutical businesses needed new markets to break through the stalemate, so they turned their attention to vitamins and health tonics as general pharmaceuticals, as these were suitable for mass production and mass consumption. The modernized patent medicine market after the Opening of Korea was transformed into the contemporized general pharmaceuticals market equipped with the up-to-date facilities and technology in 1960s. Pharmaceutical businesses had to advertise these new products extensively and reform the distribution structure to achieve high profits. With the introduction of TV broadcasting, these businesses invested in TV advertising and generated sizable sales figures. They also established retail pharmacy and chain stores to reform the distribution structure. The end result was a dramatic expansion of the general pharmaceuticals market. The

[The Korean Pharmaceutical Industry and the Expansion of the General Pharmaceuticals Market in the 1950-1960s].

Science.gov (United States)

Sihn, Kyu-Hwan

2015-12-01

After the Liberation, the Korean economy was dependent on relief supplies and aid after the ruin of the colonial regime and war. The pharmaceutical business also searched for their share in the delivery of military supplies and the distribution of relief supplies. The supply-side pharmaceutical policy made the pharmaceutical market a wholesale business. The gravity of the situation led to an increased importation of medical supplies, and wholesalers took the lead in establishing the distribution structure, whereas consumers and pharmaceutical business were relatively intimidated. The aid provided by the International Cooperation Administration (ICA) marked a turning point in the Korean pharmaceutical industry after the middle of the 1950s. ICA supplied raw materials and equipment funds, while the pharmaceutical business imported advanced technology and capital. The government invited the local production of medical substances, whereas pharmaceutical businesses replaced imported medical substances with locally produced antibiotics. After the 1960s, the production of antibiotics reached saturation. Pharmaceutical businesses needed new markets to break through the stalemate, so they turned their attention to vitamins and health tonics as general pharmaceuticals, as these were suitable for mass production and mass consumption. The modernized patent medicine market after the Opening of Korea was transformed into the contemporized general pharmaceuticals market equipped with the up-to-date facilities and technology in 1960s. Pharmaceutical businesses had to advertise these new products extensively and reform the distribution structure to achieve high profits. With the introduction of TV broadcasting, these businesses invested in TV advertising and generated sizable sales figures. They also established retail pharmacy and chain stores to reform the distribution structure. The end result was a dramatic expansion of the general pharmaceuticals market. The market for

Adjuvant Chemoradiation Therapy After Pancreaticoduodenectomy in Elderly Patients With Pancreatic Adenocarcinoma

International Nuclear Information System (INIS)

Horowitz, David P.; Hsu, Charles C.; Wang Jingya; Makary, Martin A.; Winter, Jordan M.; Robinson, Ray; Schulick, Richard D.; Cameron, John L.; Pawlik, Timothy M.; Herman, Joseph M.

2011-01-01

Purpose: To evaluate the efficacy of adjuvant chemoradiation therapy (CRT) for pancreatic adenocarcinoma patients ≥75 years of age. Methods: The study group of 655 patients underwent pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma at the Johns Hopkins Hospital over a 12-year period (8/30/1993 to 2/28/2005). Demographic characteristics, comorbidities, intraoperative data, pathology data, and patient outcomes were collected and analyzed by adjuvant treatment status and age ≥75 years. Cox proportional hazards analysis determined clinical predictors of mortality and morbidity. Results: We identified 166 of 655 (25.3%) patients were ≥75 years of age and 489 of 655 patients (74.7%) were <75 years of age. Forty-nine patients in the elderly group (29.5%) received adjuvant CRT. For elderly patients, node-positive metastases (p = 0.008), poor/anaplastic differentiation (p = 0.012), and undergoing a total pancreatectomy (p = 0.010) predicted poor survival. The 2-year survival for elderly patients receiving adjuvant therapy was improved compared with surgery alone (49.0% vs. 31.6%, p = 0.013); however, 5-year survival was similar (11.7% vs. 19.8%, respectively, p = 0.310). After adjusting for major confounders, adjuvant therapy in elderly patients had a protective effect with respect to 2-year survival (relative risk [RR] 0.58, p = 0.044), but not 5-year survival (RR 0.80, p = 0.258). Among the nonelderly, CRT was significantly associated with 2-year survival (RR 0.60, p < 0.001) and 5-year survival (RR 0.69, p < 0.001), after adjusting for confounders. Conclusions: Adjuvant therapy after PD is significantly associated with increased 2-year but not 5-year survival in elderly patients. Additional studies are needed to select which elderly patients are likely to benefit from adjuvant CRT.

Pharmaceutical Formulation Facilities as Sources of Opioids and Other Pharmaceuticals to Wastewater Treatment Plant Effluents

Science.gov (United States)

2010-01-01

Facilities involved in the manufacture of pharmaceutical products are an under-investigated source of pharmaceuticals to the environment. Between 2004 and 2009, 35 to 38 effluent samples were collected from each of three wastewater treatment plants (WWTPs) in New York and analyzed for seven pharmaceuticals including opioids and muscle relaxants. Two WWTPs (NY2 and NY3) receive substantial flows (>20% of plant flow) from pharmaceutical formulation facilities (PFF) and one (NY1) receives no PFF flow. Samples of effluents from 23 WWTPs across the United States were analyzed once for these pharmaceuticals as part of a national survey. Maximum pharmaceutical effluent concentrations for the national survey and NY1 effluent samples were generally effluent had median concentrations ranging from 3.4 to >400 μg/L. Maximum concentrations of oxycodone (1700 μg/L) and metaxalone (3800 μg/L) in samples from NY3 effluent exceeded 1000 μg/L. Three pharmaceuticals (butalbital, carisoprodol, and oxycodone) in samples of NY2 effluent had median concentrations ranging from 2 to 11 μg/L. These findings suggest that current manufacturing practices at these PFFs can result in pharmaceuticals concentrations from 10 to 1000 times higher than those typically found in WWTP effluents. PMID:20521847

Role of adjuvant radiotherapy in granulosa cell tumors of the ovary.

Science.gov (United States)

Hauspy, Jan; Beiner, Mario E; Harley, Ian; Rosen, Barry; Murphy, Joan; Chapman, William; Le, Lisa W; Fyles, Anthony; Levin, Wilfred

2011-03-01

To review the role of adjuvant radiotherapy (RT) in the outcome and recurrence patterns of granulosa cell tumors (GCTs) of the ovary. The records of all patients with GCTs referred to the Princess Margaret Hospital University Health Network between 1961 and 2006 were retrospectively reviewed. The patient, tumor, and treatment factors were assessed by univariate and multivariate analyses using disease-free survival (DFS) as the endpoint. A total of 103 patients with histologically confirmed GCTs were included in the present study. The mean duration of follow-up was 100 months (range, 1-399). Of the 103 patients, 31 received adjuvant RT. A total of 39 patients developed tumor recurrence. The tumor size, incidence of intraoperative rupture, and presence of concurrent endometrial cancer were not significant risk factors for DFS. The median DFS was 251 months for patients who underwent adjuvant RT compared with 112 months for patients who did not (p=.02). On multivariate analysis, adjuvant RT remained a significant prognostic factor for DFS (p=.004). Of the 103 patients, 12 had died and 44 were lost to follow-up. Ovarian GCTs can be indolent, with patients achieving long-term survival. In our series, adjuvant RT resulted in a significantly longer DFS. Ideally, randomized trials with long-term follow-up are needed to define the role of adjuvant RT for ovarian GCTs. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

A clinically applicable adjuvant for an atherosclerosis vaccine in mice.

Science.gov (United States)

Kobiyama, Kouji; Vassallo, Melanie; Mitzi, Jessica; Winkels, Holger; Pei, Hong; Kimura, Takayuki; Miller, Jacqueline; Wolf, Dennis; Ley, Klaus

2018-06-22

Vaccination with MHC-II-restricted peptides from Apolipoprotein B (ApoB) with complete and incomplete Freund's adjuvant (CFA/IFA) is known to protect mice from atherosclerosis. This vaccination induces antigen-specific IgG1 and IgG2c antibody responses and a robust CD4 T cell response in lymph nodes. However, CFA/IFA cannot be used in humans. To find a clinically applicable adjuvant, we tested the effect of vaccinating Apoe-deficient mice with ApoB peptide P6 (TGAYSNASSTESASY). In a broad screening experiment, Addavax, a squalene oil similar to MF59, was the only adjuvant that showed similar efficacy as CFA/IFA. This was confirmed in a confirmation experiment for both the aortic arch and whole aorta analyzed by en face analysis after atherosclerotic lesion staining. Mechanistically, restimulated peritoneal cells from mice immunized with P6 in Addavax released significant amounts of IL-10. Unlike P6 in CFA/IFA, vaccination with P6 in Addavax did not induce any detectable IgG1 or IgG2c antibodies to P6. These data suggest that squalene-based adjuvants such as MF59 are good candidate adjuvants for developing a clinically effective atherosclerosis vaccine. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Adjuvant chemotherapy for gastric cancer: Current evidence and future challenges

Science.gov (United States)

Miceli, Rosalba; Tomasello, Gianluca; Bregni, Giacomo; Di Bartolomeo, Maria; Pietrantonio, Filippo

2014-01-01

Gastric cancer still represents one of the major causes of cancer mortality worldwide. Patients survival is mainly related to stage, with a high proportion of patients with metastatic disease at presentation. Thus, the cure rate largely depend upon surgical resection. Despite the additional, albeit small, benefit of adjuvant chemotherapy has been clearly demonstrated, no general consensus has been reached on the best treatment option. Moreover, the narrow therapeutic index of adjuvant chemotherapy (i.e., limited survival benefit with considerable toxicity) requires a careful assessment of expected risks and benefits for individual patients. Treatment choices vary widely based on the different geographic areas, with chemotherapy alone more often preferred in Europe or Asia and chemoradiotherapy in the United States. In the present review we discuss the current evidence and future challenges regarding adjuvant chemotherapy in curatively resected gastric cancer with particular emphasis on the recently completed landmark studies and meta-analyses. The most recent patient-level meta-analysis demonstrated the benefit of adjuvant chemotherapy over curative surgery; the same Authors also showed that disease-free survival may be used as a surrogate end-point for overall survival. We finally discuss future research issues such as the need of economic evaluations, development of prognostic or predictive biomarkers, and the unmet clinical need of trials comparing perioperative chemotherapy with adjuvant treatment. PMID:24782604

Novel adjuvants & delivery vehicles for vaccines development: a road ahead.

Science.gov (United States)

Mohan, Teena; Verma, Priyanka; Rao, D Nageswara

2013-11-01

The pure recombinant and synthetic antigens used in modern day vaccines are generally less immunogenic than older style live/attenuated and killed whole organism vaccines. One can improve the quality of vaccine production by incorporating immunomodulators or adjuvants with modified delivery vehicles viz. liposomes, immune stimulating complexes (ISCOMs), micro/nanospheres apart from alum, being used as gold standard. Adjuvants are used to augment the effect of a vaccine by stimulating the immune system to respond to the vaccine, more vigorously, and thus providing increased immunity to a particular disease. Adjuvants accomplish this task by mimicking specific sets of evolutionary conserved molecules which include lipopolysaccharides (LPS), components of bacterial cell wall, endocytosed nucleic acids such as dsRNA, ssDNA and unmethylated CpG dinucleotide containing DNA. This review provides information on various vaccine adjuvants and delivery vehicles being developed to date. From literature, it seems that the humoral immune responses have been observed for most adjuvants and delivery platforms while viral-vector, ISCOMs and Montanides have shown cytotoxic T-cell response in the clinical trials. MF59 and MPL® have elicited Th1 responses, and virus-like particles (VLPs), non-degradable nanoparticle and liposomes have also generated cellular immunity. Such vaccine components have also been evaluated for alternative routes of administration with clinical success reported for intranasal delivery of viral-vectors and proteosomes and oral delivery of VLP vaccines.

Adjuvant therapy for gastric cancer: what have we learned since INT0116?

Science.gov (United States)

Jácome, Alexandre A; Sankarankutty, Ajith K; dos Santos, José Sebastião

2015-04-07

Gastric cancer is one of the main cancer-related causes of death worldwide. The curative treatment of gastric cancer consists of tumor resection and lymphadenectomy. However, surgical treatment alone is associated with high recurrence rates. Adjuvant treatment strategies have been studied over the last decades, but there have been controversial results from the initial studies. The pivotal INT0116 study demonstrated that the use of adjuvant chemoradiotherapy with 5-fluorouracil increases relapse-free and overall survival, and it has been adopted across the Western world. The high toxicity of radiochemotherapy and suboptimal surgical treatment employed, with fewer than 10% of the patients submitted to D2 lymphadenectomy, were the main study limitations. Since its publication, other adjuvant treatment modalities have been studied, and radiochemotherapy is being refined to improve its efficacy and safety. A multimodal approach has been demonstrated to significantly increase relapse-free and overall survival, and it can be offered in the form of perioperative chemotherapy, adjuvant chemoradiotherapy or adjuvant chemotherapy, regardless of the extent of lymphadenectomy. The objective of the present review is to report the major advances obtained in the last decades in the adjuvant treatment of gastric cancer as well as the perspectives of treatment based on recent knowledge of the molecular biology of the disease.

Development of Novel Protocol for Preclinical Monitoring the Release of Adjuvants Encapsulated Mucosal Delivery Carriers

Directory of Open Access Journals (Sweden)

Mohamed Ibrahim-Saeed

2015-12-01

Full Text Available This work contributes in vaccines down-stream process by introducing a novel platform for in-vitro monitoring of vaccine-adjuvant delivery profile as a crucial preclinical optimizing step in mucosal vaccines. Nano and micro particles of Calcium phosphate (Cap vaccine-adjuvant were encapsulated in Chitosan and Alginate polymeric carriers. Adjuvants release profiles monitored in a permeable bag at 37°C, pH 2, incubated in isotonic buffer for 96 hours. The released Calcium in the outer buffer was monitored and compared in-addition to the carrier’s swelling and biophysical properties. The adjuvants and carriers did not interfere with the proliferation of cultured hepatocytes an indicator of their safe use; Chitosan’s viscosity and swelling were higher than Alginate. Chitosan’s Zeta-potential was significantly high positive, while Cap and Alginate were negative. The prepared CaP and Chitosan particles were in nano-size, while the ready-made CaP adjuvant and Alginate were in micro-size using zeta-seizer and scanning electron-micrograph. The release of nano-size particle was in ascending, extended and controlled manner compared to micro-size adjuvant. Moreover, nano-adjuvant release profile from Chitosan was superior compared to Alginate. The core controlling factors in vaccine-adjuvant sustained release includes; smaller adjuvant particles (nano-size, carrier’s low swelling, high viscosity and importantly carrier-adjuvant entrapment reversibility. Chitosan offers sustained ascending superior capacity in releasing Nano-Cap adjuvant. This novel in-vitro pre-clinical study answer a crucial downstream preparative step for optimizing mucosal vaccines before their direct routine in-vivo trial on animal regardless of adjuvant’s particle size or delivery kinetics.

Cardiac monitoring during adjuvant trastuzumab therapy: Guideline adherence in clinical practice

NARCIS (Netherlands)

Visser, Annemiek; van de Ven, Eline M. W.; Ruczynski, Larissa I. A.; Blaisse, Reinoud J. B.; van Halteren, Henk K.; Aben, Katja; van Laarhoven, Hanneke W. M.

2016-01-01

Cardiotoxicity is an important adverse effect of adjuvant breast cancer treatment with trastuzumab and three monthly left ventricular ejection fraction (LVEF) monitoring is considered mandatory. The purpose of this study was to gain insight into LVEF monitoring during adjuvant trastuzumab treatment

Randomized trial of adjuvant ovarian suppression in 926 premenopausal patients with early breast cancer treated with adjuvant chemotherapy.

Science.gov (United States)

Arriagada, R; Lê, M G; Spielmann, M; Mauriac, L; Bonneterre, J; Namer, M; Delozier, T; Hill, C; Tursz, T

2005-03-01

The aim of this multicenter trial was to evaluate the role of ovarian suppression in patients with early breast cancer previously treated with local surgery and adjuvant chemotherapy. Nine hundred and twenty-six premenopausal patients with completely resected breast cancer and either axillary node involvement or histological grade 2 or 3 tumors were randomized after surgery to adjuvant chemotherapy alone (control arm) or adjuvant chemotherapy plus ovarian suppression (ovarian suppression arm). Ovarian suppression was obtained by either radiation-induced ovarian ablation or triptorelin for 3 years. The analyses were performed with Cox models stratified by center. Median follow-up was 9.5 years. Mean age was 43 years. Ninety per cent of patients had histologically proven positive axillary nodes, 63% positive hormonal receptors and 77% had received an anthracycline-based chemotherapy regimen. Ovarian suppression was by radiation-induced ovarian ablation (45% of patients) or with triptorelin (48%). At the time of randomization, all patients had regular menses or their follicle-stimulating hormone and estradiol levels indicated a premenopausal status. The 10-year disease-free survival rates were 49% [95% confidence interval (CI) 44% to 54%] in both arms (P = 0.51). The 10-year overall survival rates were 66% (95% CI 61% to 70%) for the ovarian suppression arm and 68% (95% CI 63% to 73%) for the control arm (P = 0.19). There were no variations in the treatment effect according to age, hormonal receptor status or ovarian suppression modality. However, in patients suppression significantly decreased the risk of recurrence (P = 0.01). The results of this trial, after at least 10 years of follow-up, do not favor the use of ovarian suppression after adjuvant chemotherapy. The potential beneficial effect in younger women with hormono-dependent tumors should be further assessed.

Management of Pediatric Myxopapillary Ependymoma: The Role of Adjuvant Radiation

Energy Technology Data Exchange (ETDEWEB)

Agbahiwe, Harold C.; Wharam, Moody [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Batra, Sachin [Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Cohen, Kenneth [Division of Pediatric Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Terezakis, Stephanie A., E-mail: sterezak@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

2013-02-01

Introduction: Myxopapillary ependymoma (MPE) is a rare tumor in children. The primary treatment is gross total resection (GTR), with no clearly defined role for adjuvant radiation therapy (RT). Published reports, however, suggest that children with MPE present with a more aggressive disease course. The goal of this study was to assess the role of adjuvant RT in pediatric patients with MPE. Methods: Sixteen patients with MPE seen at Johns Hopkins Hospital (JHH) between November 1984 and December 2010 were retrospectively reviewed. Fifteen of the patients were evaluable with a mean age of 16.8 years (range, 12-21 years). Kaplan-Meier curves and descriptive statistics were used for analysis. Results: All patients received surgery as the initial treatment modality. Surgery consisted of either a GTR or a subtotal resection (STR). The median dose of adjuvant RT was 50.4 Gy (range, 45-54 Gy). All patients receiving RT were treated at the involved site. After a median follow-up of 7.2 years (range, 0.75-26.4 years), all patients were alive with stable disease. Local control at 5 and 10 years was 62.5% and 30%, respectively, for surgery alone versus 100% at both time points for surgery and adjuvant RT. Fifty percent of the patients receiving surgery alone had local failure. All patients receiving STR alone had local failure compared to 33% of patients receiving GTR alone. One patient in the surgery and adjuvant RT group developed a distant site of recurrence 1 year from diagnosis. No late toxicity was reported at last follow-up, and neurologic symptoms either improved or remained stable following surgery with or without RT. Conclusions: Adjuvant RT improved local control compared to surgery alone and should be considered after surgical resection in pediatric patients with MPE.

[Critical analysis of reference studies on aluminium-based adjuvants toxicokinetics].

Science.gov (United States)

Masson, J-D; Crépeaux, G; Authier, F-J; Exley, C; Gherardi, R K

2017-07-01

We reviewed the three reference toxicokinetic studies commonly used to suggest innocuity of aluminum (Al)-based adjuvants. A single experimental study was carried out using isotopic 26 Al (Flarend et al., 1997). This study ignored adjuvant cell capture. It was conducted over a short period of time (28 days) and used only two rabbits per adjuvant. At the endpoint, Al retention was 78% for aluminum phosphate and 94% for aluminum hydroxide, both results being incompatible with quick elimination of vaccine-derived Al in urines. Tissue distribution analysis omitted three important retention sites: the injected muscle, the draining lymph node and bone. Two theoretical studies have evaluated the potential risk of vaccine Al in infants, by reference to the oral Minimal Risk Level (MRL) extrapolated from animal studies. Keith et al., 2002 used a too high MRL (2mg/kg/d), an erroneous model of 100% immediate absorption of vaccine Al, and did not consider renal and blood-brain barrier immaturity. Mitkus et al. (2011) only considered absorbed Al, with erroneous calculations of absorption duration. They ignored particulate Al captured by immune cells, which play a role in systemic diffusion and the neuro-inflammatory potential of the adjuvant. MRL they used was both inappropriate (oral Al vs injected adjuvant) and far too high (1mg/kg/d) with regard to experimental studies of Al-induced memory and behavioral changes. Both paucity and serious weaknesses of these studies strongly suggest that novel experimental studies of Al adjuvants toxicokinetics should be performed on the long-term, including post-natal and adult exposures, to ensure innocuity and restore population confidence in Al-containing vaccines. Copyright © 2017 Académie Nationale de Pharmacie. All rights reserved.

Extended Adjuvant Therapy for Breast Cancer

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An NCI Cancer Currents blog on findings from a recent clinical trial which showed that extending adjuvant therapy with an aromatase inhibitor can have important benefits for some women with early-stage cancer.

Pharmaceutical compounds in drinking water

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Vikas Chander

2016-06-01

Full Text Available Pharmaceutical products and their wastes play a major role in the degradation of environment. These drugs have positive as well as negative consequences on different environmental components including biota in different ways. Many types of pharmaceutical substances have been detected with significant concentrations through various advanced instrumental techniques in surface water, subsurface water, ground water, domestic waste water, municipal waste water and industrial effluents. The central as well as state governments in India are providing supports by creating excise duty free zones to promote the pharmaceutical manufacturers for their production. As a result, pharmaceutical companies are producing different types of pharmaceutical products at large scale and also producing complex non-biodegradable toxic wastes byproducts and releasing untreated or partially treated wastes in the environment in absence of strong regulations. These waste pollutants are contaminating all types of drinking water sources. The present paper focuses on water quality pollution by pharmaceutical pollutants, their occurrences, nature, metabolites and their fate in the environment.

Adjuvant chemotherapy in soft tissue sarcomas…Conflicts, consensus, and controversies

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Jyoti Bajpai

2016-01-01

Full Text Available Soft tissue sarcomas (STSs are an uncommon and diverse group of more than 50 mesenchymal malignancies. Each of these histologic subtypes represents a unique disease with distinct biologic behavior and varying sensitivity to chemotherapy. The judicious use of adjuvant/neoadjuvant chemotherapy along with surgery and radiation in the treatment of localized STS has a role in improving patient outcomes by decreasing local and distant recurrences. There is evidence that the use of adjuvant chemotherapy to a mixed cohort of chemo sensitive and insensitive sarcoma subtypes results in limited benefit. Therefore, it is of paramount importance to identify the subpopulation with high metastatic potential and to identify effective histology-specific treatment options to these patients. Present perspective, will focus on the rationale for adjuvant chemotherapy in sarcoma, with emphasis on the histology driven chemotherapy. It will outline key therapeutic opportunities and hurdles in adjuvant medical treatment of sarcoma, focusing on specific subtypes that are on the verge of new breakthroughs, as well as those in which promise has not lived up to expectations.

Intraperitoneal P-32 for adjuvant and consolidative therapy in ovarian carcinoma

International Nuclear Information System (INIS)

Condra, Kellie S.; Mendenhall, William M.; Morgan, Linda S.; Freeman, Debra E.; Marcus, Robert B.; Hagan, Michael P.

1996-01-01

Purpose/Objective: To determine the role of intraperitoneal radioactive chromic phosphate (P-32) in the treatment of patients with ovarian carcinoma. Survival results, patterns of recurrence, and treatment morbidity are reported for patients treated adjuvantly after primary surgery and for patients treated with the intent of consolidation after second-look laparotomy. Materials and Methods: Between 1976 and 1993, 25 patients with ovarian carcinoma were treated with 15 mCi P-32 as adjuvant therapy and 43 patients received P-32 as consolidation after second-look laparotomy. The majority of patients (13 of 19) treated adjuvantly had high-risk early-stage disease (IAG 3, IBG 2-3, IC) or more advanced stages (6 patients). Thirty-nine patients received consolidative P-32 after negative second-look laparotomy (35 Stage II-IV and 4 Stage I) and 4 Stage III patients were treated after positive second-look laparotomy. All patients had 2-year minimum follow-up (median, 7.9 years). Results: Ten-year abdominal control and cause-specific survival rates for adjuvant P-32 were 83% and 82%, respectively. For patients treated with consolidative P-32, 5-year abdominal control and cause-specific survival rates were 65% and 78%, respectively. The 5-year cause-specific survival rate for 35 patients with Stage II-IV disease treated with consolidative P-32 after negative second-look laparotomy was 81%. A component of peritoneal failure was the primary mode of recurrence (15 of 22 failures). Four patients required surgical intervention for small-bowel obstruction. No patients died of treatment-related complications. Conclusion: P-32 is well tolerated with acceptable toxicity. In comparing our results to the literature, adjuvant P-32 appears to offer improved cause-specific survival compared with observation alone and equivalent cause-specific survival compared with adjuvant chemotherapy. Consolidative P-32 after negative second-look laparotomy resulted in improved 5-year cause

FORENSIC AND PHARMACEUTICAL RESEARCH OF ORGANIZATION OF AVAILABILITY OF THE MEDICINES FOR PATIENTS WITH MALIGNANCIES IN THE UNITED STATES

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Shapovalov VV (Jr.

2016-09-01

Full Text Available Introduction. The incidence of cancer in recent years has increased significantly. It is therefore particularly important today is the issue of provision for patients with malignancies with drugs. It is important to research the level of organization of availability of the anesthetic therapy to ensure the availability of pharmacotherapy for cancer patients worldwide. Material and methods. For the purpose of the study analyzed legislation, regulations of some states in the US that provide availability of narcotic analgesic drugs for patients with malignant neoplasms. The paper used the following methods: comparative, documentary, legal, medical, pharmaceutical and graphical analysis. Results and discussion. Noted the increase in expenditure on pharmaceutical provision for patients with malignancies on an outpatient basis in the US. During the study of the legislative and regulatory acts of the USA found that payments for treatment possible by insurance companies as part of the agreement, which in turn depend on the patient’s age, number of family members, their total income and so on. Coupons can be used to pay for the cost of medicines, but not all pharmacies accept coupons. There are charities with funds which are partially covered for the cost of chemotherapy and adjuvant therapy (analgesics, antiemetic, antipsychotics, drugs. Found, that in New York doctor may prescribe analgesic medication to the patient without limitation in the frequency and dose. It is not therapeutic use of analgesics, their improper accounting, drug addiction patient has contraindications to the prescription of narcotic analgesic drugs with malignant neoplasms. Reviewed examples from forensic and pharmaceutical practice, pharmaceutical violation of the US laws that regulate the accessibility of patients with malignancies to narcotic analgesic drugs. So, there have been cases of fake prescriptions for narcotic drugs, selling drugs, the shelf life has expired. Police of

Supramolecular Pharmaceutical Sciences: A Novel Concept Combining Pharmaceutical Sciences and Supramolecular Chemistry with a Focus on Cyclodextrin-Based Supermolecules.

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Higashi, Taishi; Iohara, Daisuke; Motoyama, Keiichi; Arima, Hidetoshi

2018-01-01

Supramolecular chemistry is an extremely useful and important domain for understanding pharmaceutical sciences because various physiological reactions and drug activities are based on supramolecular chemistry. However, it is not a major domain in the pharmaceutical field. In this review, we propose a new concept in pharmaceutical sciences termed "supramolecular pharmaceutical sciences," which combines pharmaceutical sciences and supramolecular chemistry. This concept could be useful for developing new ideas, methods, hypotheses, strategies, materials, and mechanisms in pharmaceutical sciences. Herein, we focus on cyclodextrin (CyD)-based supermolecules, because CyDs have been used not only as pharmaceutical excipients or active pharmaceutical ingredients but also as components of supermolecules.

Effects of adjuvants on IgG subclasses elicited by virus-like Particles

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Visciano Maria Luisa

2012-01-01

Full Text Available Abstract Background Virus-Like Particles (VLPs represent an efficient strategy to present and deliver conformational antigens to the immune system, inducing both arms of the adaptive immune response. Moreover, their particulate structure surrounded by cell membrane provides an adjuvanted effect to VLP-based immunizations. In the present study, the elicitation of different patterns of IgG subclasses by VLPs, administered in CpG ODN1826 or poly(I:C adjuvants, has been evaluated in an animal model. Results Adjuvanted VLPs elicited a higher titer of total specific IgG compared to VLPs alone. Furthermore, while VLPs alone induced a balanced TH2 pattern, VLPs formulated with either adjuvant elicited a TH1-biased IgG subclasses (IgG2a and IgG3, with poly(I:C more potent than CpG ODN1826. Conclusions The results confirmed that adjuvants efficiently improve antigen immunogenicity and represent a suitable strategy to skew the adaptive immune response toward the differentiation of the desired T helper subset, also using VLPs as antigen.

[Hospital pharmaceutical practice in prison].

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Harcouët, L

2010-09-01

Since 1994, hospital pharmaceutical teams have been in charge of pharmaceutical tasks in "unités de consultation et de soins ambulatoires" (UCSA), which are hospital consulting care units in French prisons. In 2008, pharmaceutical team in Parisian prisons received 6500 prescriptions and prepared 85,000 nominative bags containing drugs. Prisoners were 1.3% to receive treatments against HIV, 8.2% cardiovascular drugs, 7.2% opioid substitution treatments, and 52.9% psychoactive drugs, including 39.3% hypnotics, 40.5% anxiolytics, 11.3% antidepressants and 12.2% neuroleptics. In prison, the dichotomy between somatic and mental care is marked, attitudes of prisoners about their medicines are complex (important claims, embezzlement, etc.) and it is difficult for law defendants to maintain treatment confidentiality and to prepare prison outing in terms of health. To attenuate the heterogeneity of drug distribution systems in French prisons, we propose pharmaceutical analysis of prescriptions and nominative dispensation, computerization in UCSA in coordination with hospitals, a better contribution of prison medical and pharmaceutical staff in hospital "drug committees" and the redaction of pharmaceutical guidelines. Acting in concert with multidisciplinary medical staff in UCSA, pharmaceutical teams have to develop epidemiological studies to improve knowledge in prisoner's health and also prevention and health care in prison. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Benefit of adjuvant chemotherapy in patients with T4 UICC II colon cancer.

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Teufel, Andreas; Gerken, Michael; Hartl, Janine; Itzel, Timo; Fichtner-Feigl, Stefan; Stroszczynski, Christian; Schlitt, Hans Jürgen; Hofstädter, Ferdinand; Klinkhammer-Schalke, Monika

2015-05-20

Colorectal cancer is the third most common cancer and a major cause of morbidity and mortality worldwide. Adjuvant chemotherapy is considered the standard of care in patients with UICC stage III colon cancer after R0 resection. Adjuvant therapy was not shown to be beneficial in patients with UICC stage II colon cancer. However, there is an ongoing discussion as to whether adjuvant chemotherapy may be beneficial for a subgroup of UICC II patients in a "high-risk situation" (such as T4). We investigated a Bavarian population-based (2.1 million inhabitants) cohort of 1937 patients with UICC II CRC treated between 2002 and 2012 in regard of the benefit of adjuvant chemotherapy for large (T4) tumors. Patients older than 80 years of age were excluded. Of 1937 patients, 240 had a T4 tumor (12%); 77 of all T4 patients received postoperative chemotherapy (33%). Kaplan-Meier analysis and Cox regression models were used for survival analyses. Patients with a T4 tumor who received postoperative chemotherapy had a highly significant survival benefit in respect of overall survival (pbenefit from adjuvant treatment. Chemotherapy, age at diagnosis, and tumor grading remained independent risk factors in the multivariate cox regression analysis. Our retrospective study demonstrated the significant benefit of adjuvant chemotherapy in the T4 subgroup of patients with UICC II colon cancer. Our data suggest that adjuvant chemotherapy should be seriously considered in these patients.

Technology transfer of oil-in-water emulsion adjuvant manufacturing for pandemic influenza vaccine production in Romania: Preclinical evaluation of split virion inactivated H5N1 vaccine with adjuvant.

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Stavaru, Crina; Onu, Adrian; Lupulescu, Emilia; Tucureanu, Catalin; Rasid, Orhan; Vlase, Ene; Coman, Cristin; Caras, Iuliana; Ghiorghisor, Alina; Berbecila, Laurentiu; Tofan, Vlad; Bowen, Richard A; Marlenee, Nicole; Hartwig, Airn; Bielefeldt-Ohmann, Helle; Baldwin, Susan L; Van Hoeven, Neal; Vedvick, Thomas S; Huynh, Chuong; O'Hara, Michael K; Noah, Diana L; Fox, Christopher B

2016-04-02

Millions of seasonal and pandemic influenza vaccine doses containing oil-in-water emulsion adjuvant have been administered in order to enhance and broaden immune responses and to facilitate antigen sparing. Despite the enactment of a Global Action Plan for Influenza Vaccines and a multi-fold increase in production capabilities over the past 10 years, worldwide capacity for pandemic influenza vaccine production is still limited. In developing countries, where routine influenza vaccination is not fully established, additional measures are needed to ensure adequate supply of pandemic influenza vaccines without dependence on the shipment of aid from other, potentially impacted first-world countries. Adaptation of influenza vaccine and adjuvant technologies by developing country influenza vaccine manufacturers may enable antigen sparing and corresponding increases in global influenza vaccine coverage capacity. Following on previously described work involving the technology transfer of oil-in-water emulsion adjuvant manufacturing to a Romanian vaccine manufacturing institute, we herein describe the preclinical evaluation of inactivated split virion H5N1 influenza vaccine with emulsion adjuvant, including immunogenicity, protection from virus challenge, antigen sparing capacity, and safety. In parallel with the evaluation of the bioactivity of the tech-transferred adjuvant, we also describe the impact of concurrent antigen manufacturing optimization activities. Depending on the vaccine antigen source and manufacturing process, inclusion of adjuvant was shown to enhance and broaden functional antibody titers in mouse and rabbit models, promote protection from homologous virus challenge in ferrets, and facilitate antigen sparing. Besides scientific findings, the operational lessons learned are delineated in order to facilitate adaptation of adjuvant technologies by other developing country institutes to enhance global pandemic influenza preparedness.

Melatonin and Fertoprotective Adjuvants: Prevention against Premature Ovarian Failure during Chemotherapy.

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Jang, Hoon; Hong, Kwonho; Choi, Youngsok

2017-06-07

Premature ovarian failure is one of the side effects of chemotherapy in pre-menopausal cancer patients. Preservation of fertility has become increasingly important in improving the quality of life of completely recovered cancer patients. Among the possible strategies for preserving fertility such as ovarian tissue cryopreservation, co-treatment with a pharmacological adjuvant is highly effective and poses less of a burden on the human body. Melatonin is generally produced in various tissues and acts as a universally acting antioxidant in cells. Melatonin is now more widely used in various biological processes including treating insomnia and an adjuvant during chemotherapy. In this review, we summarize the information indicating that melatonin may be useful for reducing and preventing premature ovarian failure in chemotherapy-treated female patients. We also mention that many adjuvants other than melatonin are developed and used to inhibit chemotherapy-induced infertility. This information will give us novel insights on the clinical use of melatonin and other agents as fertoprotective adjuvants for female cancer patients.

Pharmaceutical cocrystals: an overview.

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Qiao, Ning; Li, Mingzhong; Schlindwein, Walkiria; Malek, Nazneen; Davies, Angela; Trappitt, Gary

2011-10-31

Pharmaceutical cocrystals are emerging as a new class of solid drugs with improved physicochemical properties, which has attracted increased interests from both industrial and academic researchers. In this paper a brief and systematic overview of pharmaceutical cocrystals is provided, with particular focus on cocrystal design strategies, formation methods, physicochemical property studies, characterisation techniques, and recent theoretical developments in cocrystal screening and mechanisms of cocrystal formations. Examples of pharmaceutical cocrystals are also summarised in this paper. Copyright © 2011 Elsevier B.V. All rights reserved.

Effect of different adjuvant formulations on the immunogenicity and protective effect of a live Mycoplasma hyopneumoniae vaccine after intramuscular inoculation.

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Xiong, Qiyan; Wei, Yanna; Xie, Haidong; Feng, Zhixin; Gan, Yuan; Wang, Chunlai; Liu, Maojun; Bai, Fangfang; Xie, Fang; Shao, Guoqing

2014-06-05

Mycoplasma hyopneumoniae (M. hyopneumoniae) vaccine strain 168 is an intrapulmonically injected attenuated live vaccine that is available in the Chinese market. The aim of this study was to develop suitable adjuvants for this live vaccine to provide effective protection after intramuscular inoculation. Several adjuvant components were screened to assess their toxicity for the live vaccine, and various adjuvant formulations were then designed and prepared. Vaccines supplemented with these adjuvants were used to immunize mice intramuscularly to assess the capacity of the adjuvants to induce a specific immune response. The screened formulations were then evaluated in pigs. Seven of the eight adjuvant components did not affect the viability of the live vaccine, and seven different adjuvant formulations were then designed. In mice, the ISCOM-matrix adjuvant and the levamisole-chitosan mixture adjuvant significantly enhanced serum IgG responses against M. hyopneumoniae, while lymphocyte proliferation was enhanced by the ISCOM-matrix adjuvant, the carbomer-astragalus polysaccharide mixture adjuvant and an oil-in-water emulsion adjuvant. These four adjuvants were evaluated in pigs. Enhancement of specific lymphocyte proliferation responses was observed in the groups vaccinated with the ISCOM-matrix adjuvant and the carbomer-astragalus polysaccharide mixture adjuvant. Significant enhancement of serum IgG antibody production was observed before challenge in pigs vaccinated with the carbomer-astragalus polysaccharide mixture adjuvant and the levamisole-chitosan mixture adjuvant, while after challenge, all of the animals that received vaccines containing adjuvants had higher antibody concentrations against M. hyopneumoniae than unvaccinated animals. Animals inoculated with a vaccine containing the ISCOM-matrix adjuvant (median score 3.57) or the carbomer-astragalus polysaccharide mixture adjuvant (median score 5.28) had reduced lesion scores compared to unvaccinated animals

Designing CAF-adjuvanted dry powder vaccines: spray drying preserves the adjuvant activity of CAF01.

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Ingvarsson, Pall Thor; Schmidt, Signe Tandrup; Christensen, Dennis; Larsen, Niels Bent; Hinrichs, Wouter Leonardus Joseph; Andersen, Peter; Rantanen, Jukka; Nielsen, Hanne Mørck; Yang, Mingshi; Foged, Camilla

2013-05-10

Dry powder vaccine formulations are highly attractive due to improved storage stability and the possibility for particle engineering, as compared to liquid formulations. However, a prerequisite for formulating vaccines into dry formulations is that their physicochemical and adjuvant properties remain unchanged upon rehydration. Thus, we have identified and optimized the parameters of importance for the design of a spray dried powder formulation of the cationic liposomal adjuvant formulation 01 (CAF01) composed of dimethyldioctadecylammonium (DDA) bromide and trehalose 6,6'-dibehenate (TDB) via spray drying. The optimal excipient to stabilize CAF01 during spray drying and for the design of nanocomposite microparticles was identified among mannitol, lactose and trehalose. Trehalose and lactose were promising stabilizers with respect to preserving liposome size, as compared to mannitol. Trehalose and lactose were in the glassy state upon co-spray drying with the liposomes, whereas mannitol appeared crystalline, suggesting that the ability of the stabilizer to form a glassy matrix around the liposomes is one of the prerequisites for stabilization. Systematic studies on the effect of process parameters suggested that a fast drying rate is essential to avoid phase separation and lipid accumulation at the surface of the microparticles during spray drying. Finally, immunization studies in mice with CAF01 in combination with the tuberculosis antigen Ag85B-ESAT6-Rv2660c (H56) demonstrated that spray drying of CAF01 with trehalose under optimal processing conditions resulted in the preservation of the adjuvant activity in vivo. These data demonstrate the importance of liposome stabilization via optimization of formulation and processing conditions in the engineering of dry powder liposome formulations. Copyright © 2013 Elsevier B.V. All rights reserved.

Suppressive effects of QFGJS, a preparation from an anti-arthritic herbal formula, on rat experimental adjuvant-induced arthritis

International Nuclear Information System (INIS)

Cai Xiong; Zhou Hua; Wong Yuenfan; Xie Ying; Liu Zhong Qiu; Jiang Zhhong; Bian Zhaoxiang; Xu Hongxi; Liu Liang

2005-01-01

To analyze the anti-arthritic effects of QFGJS (a pharmaceutical preparation from herbs) on rheumatoid arthritis, adjuvant-induced arthritis (AIA) was established in male SD rats, and two administration protocols, i.e., oral treatment with different doses of QFGJS on the day of arthritis induction or on the day when visible clinical signs of arthritis occurred, were initiated and continued until day 30. Treatments with QFGJS using both administration protocols significantly suppressed the incidence and severity of arthritis in a dose-dependent manner, showing dramatic reduction of paw swelling and ESR throughout the disease progression of AIA. Radiological and histopathological examinations showed markedly decreased tissue and bone destruction of ankle joints in the QFGJS-treated rats. The serum levels of TNF-α, IL-1β, and IL-6 were significantly decreased in the QFGJS-treated rats. QFGJS demonstrates pronounced anti-arthritic effects on AIA, indicating that this herbal preparation would be a potent candidate as a novel botanical drug for further investigation

Vaccine Adjuvant Incorporation Strategy Dictates Peptide Amphiphile Micelle Immunostimulatory Capacity.

Science.gov (United States)

Zhang, Rui; Kramer, Jake S; Smith, Josiah D; Allen, Brittany N; Leeper, Caitlin N; Li, Xiaolei; Morton, Logan D; Gallazzi, Fabio; Ulery, Bret D

2018-06-01

Current vaccine research has shifted from traditional vaccines (i.e., whole-killed or live-attenuated) to subunit vaccines (i.e., protein, peptide, or DNA) as the latter is much safer due to delivering only the bioactive components necessary to produce a desirable immune response. Unfortunately, subunit vaccines are very weak immunogens requiring delivery vehicles and the addition of immunostimulatory molecules termed adjuvants to convey protective immunity. An interesting type of delivery vehicle is peptide amphiphile micelles (PAMs), unique biomaterials where the vaccine is part of the nanomaterial itself. Due to the modularity of PAMs, they can be readily modified to deliver both vaccine antigens and adjuvants within a singular construct. Through the co-delivery of a model antigenic epitope (Ovalbumin 319-340 -OVA BT ) and a known molecular adjuvant (e.g., 2,3-dipalmitoyl-S-glyceryl cysteine-Pam 2 C), greater insight into the mechanisms by which PAMs can exert immunostimulatory effects was gained. It was found that specific combinations of antigen and adjuvant can significantly alter vaccine immunogenicity both in vitro and in vivo. These results inform fundamental design rules that can be leveraged to fabricate optimal PAM-based vaccine formulations for future disease-specific applications. Graphical Abstract.

Adjuvant-enhanced CD4 T Cell Responses are Critical to Durable Vaccine Immunity.

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Martins, Karen A O; Cooper, Christopher L; Stronsky, Sabrina M; Norris, Sarah L W; Kwilas, Steven A; Steffens, Jesse T; Benko, Jacqueline G; van Tongeren, Sean A; Bavari, Sina

2016-01-01

Protein-based vaccines offer a safer alternative to live-attenuated or inactivated vaccines but have limited immunogenicity. The identification of adjuvants that augment immunogenicity, specifically in a manner that is durable and antigen-specific, is therefore critical for advanced development. In this study, we use the filovirus virus-like particle (VLP) as a model protein-based vaccine in order to evaluate the impact of four candidate vaccine adjuvants on enhancing long term protection from Ebola virus challenge. Adjuvants tested include poly-ICLC (Hiltonol), MPLA, CpG 2395, and alhydrogel. We compared and contrasted antibody responses, neutralizing antibody responses, effector T cell responses, and T follicular helper (Tfh) cell frequencies with each adjuvant's impact on durable protection. We demonstrate that in this system, the most effective adjuvant elicits a Th1-skewed antibody response and strong CD4 T cell responses, including an increase in Tfh frequency. Using immune-deficient animals and adoptive transfer of serum and cells from vaccinated animals into naïve animals, we further demonstrate that serum and CD4 T cells play a critical role in conferring protection within effective vaccination regimens. These studies inform on the requirements of long term immune protection, which can potentially be used to guide screening of clinical-grade adjuvants for vaccine clinical development.

Influence of various forms of dialyzable leukocyte extracts on rat adjuvant arthritis

International Nuclear Information System (INIS)

Stancikova, Maria; Rovensky, Jozef; Blazickova, Stanislava; Pekarek, J.; Cech, Karel

1994-01-01

Adjuvant-induced arthritis in rats is a chronic inflammatory disease, widely as an animal model for rheumatoid arthritis. In our study the effect of various fractions of dialyzable leukocyte extract (DLE): DLE I-molecular weight below 10 kDa (commercial preparation), DLE II-molecular weight below 5 kDa (suppressor fraction), DLE III-molecular weight 5-10 kDa on rat adjuvant-induced arthritis was studied. The adjuvant arthritic (AA) rats were treated with DLE fractions i.p. in solutions containing an active substance isolated from 12.5 x 10 6 and 6.25 x 10 6 leukocytes from day 1 (adjuvant injected) through day 18, every second day (total 9 times). Various markers in inflammation, immune function and joint destruction were evaluated: hind paw volume, serum hyaluronic acid, serum albumin and biopterin in urine. All these markers showed a significant improvement after using fraction DLE II in comparison with AA controls. Fractions DLE I and DLE III influenced only some markers of inflammation and immune function. Our results demonstrated a therapeutical effect of fraction DLE II on rat adjuvant-induced arthritis. (author). 22 refs, 2 figs, 2 tabs

Adjuvants and the vaccine response to the DS-Cav1-stabilized fusion glycoprotein of respiratory syncytial virus.

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Mallika Sastry

Full Text Available Appropriate adjuvant selection may be essential to optimize the potency and to tailor the immune response of subunit vaccines. To induce protective responses against respiratory syncytial virus (RSV-a highly prevalent childhood pathogen without a licensed vaccine-we previously engineered a pre-fusion-stabilized trimeric RSV F (pre-F "DS-Cav1" immunogen, which induced high titer RSV-neutralizing antibodies, in mice and non-human primates, when formulated with adjuvants Poly (I:C and Poly (IC:LC, respectively. To assess the impact of different adjuvants, here we formulated RSV F DS-Cav1 with multiple adjuvants and assessed immune responses. Very high RSV-neutralizing antibody responses (19,006 EC50 were observed in naïve mice immunized with 2 doses of DS-Cav1 adjuvanted with Sigma adjuvant system (SAS, an oil-in-water adjuvant, plus Carbopol; high responses (3658-7108 were observed with DS-Cav1 adjuvanted with Alum, SAS alone, Adjuplex, Poly (I:C and Poly (IC:LC; and moderate responses (1251-2129 were observed with DS-Cav1 adjuvanted with the TLR4 agonist MPLA, Alum plus MPLA or AddaVax. In contrast, DS-Cav1 without adjuvant induced low-level responses (6. A balanced IgG1 and IgG2a (Th2/Th1 immune response was elicited in most of the high to very high response groups (all but Alum and Adjuplex. We also tested the immune response induced by DS-Cav1 in elderly mice with pre-existing DS-Cav1 immunity; we observed that DS-Cav1 adjuvanted with SAS plus Carbopol boosted the response 2-3-fold, whereas DS-Cav1 adjuvanted with alum boosted the response 5-fold. Finally, we tested whether a mixture of ISA 71 VG and Carbopol would enhanced the antibody response in DS-Cav1 immunized calves. While pre-F-stabilized bovine RSV F induced very high titers in mice when adjuvanted with SAS plus Carbopol, the addition of Carbopol to ISA 71 VG did not enhance immune responses in calves. The vaccine response to pre-F-stabilized RSV F is augmented by adjuvant, but the

Benefit of Adjuvant Chemotherapy After Curative Resection of Lung Metastasis in Colorectal Cancer.

Science.gov (United States)

Park, Hyung Soon; Jung, Minkyu; Shin, Sang Joon; Heo, Su Jin; Kim, Chang Gon; Lee, Min Goo; Beom, Seung Hoon; Lee, Chang Young; Lee, Jin Gu; Kim, Dae Joon; Ahn, Joong Bae

2016-03-01

The survival benefit of adjuvant chemotherapy after colorectal cancer (CRC) lung metastasectomy is uncertain. We enrolled 221 CRC patients who underwent pulmonary metastasectomy between October 2002 and July 2013, including those with previous liver metastasis that had been curatively resected. Disease-free survival (DFS) and overall survival (OS) were calculated from the day of lung metastasectomy. Among all patients, 176 (79.6%) received adjuvant chemotherapy after lung metastasectomy. Median follow-up was 34.7 months from the time of lung metastasectomy [95% confidence interval (95% CI), 7.4-90.9 months]. Patients treated with adjuvant chemotherapy had longer DFS compared with surgery alone (median 32.7 vs 11.2 months respectively, P = 0.076). Multivariate analysis revealed previous liver metastasis, preoperative carcinoembryonic antigen ≥5 ng/mL, disease-free interval chemotherapy as independent risk factors for recurrence. Low-risk patients who had 0-1 risk factors received a significant survival benefit from adjuvant chemotherapy [hazard ratio (HR) 0.54; 95% CI 0.32-0.91, P = 0.020]; however, high-risk patients with ≥2 risk factors did not (HR 1.02; 95% CI 0.48-2.14, P = 0.964). Patients treated with adjuvant chemotherapy showed no OS benefit compared with patients who received surgery alone (median 89.6 vs 86.8 months respectively, P = 0.833). CRC patients received lung metastasectomy could have a DFS benefit from adjuvant chemotherapy, especially in low-risk patients. Larger, prospective studies are needed to evaluate the role of adjuvant chemotherapy after CRC lung metastasectomy.

Cyclic GMP-AMP displays mucosal adjuvant activity in mice.

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Ivana Škrnjug

Full Text Available The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice. A characteristic of the cGAMP-induced immune response is the slightly reduced induction of interleukin-17 as a hallmark of Th17 activity--a distinct feature that is not observed with other cyclic di-nucleotide adjuvants. We further characterize the innate immune stimulation activity in vitro on murine bone marrow-derived dendritic cells and human dendritic cells. The observed results suggest the consideration of cGAMP as a candidate mucosal adjuvant for human vaccines.

Cyclic GMP-AMP displays mucosal adjuvant activity in mice.

Science.gov (United States)

Škrnjug, Ivana; Guzmán, Carlos Alberto; Rueckert, Christine; Ruecker, Christine

2014-01-01

The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP) after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice. A characteristic of the cGAMP-induced immune response is the slightly reduced induction of interleukin-17 as a hallmark of Th17 activity--a distinct feature that is not observed with other cyclic di-nucleotide adjuvants. We further characterize the innate immune stimulation activity in vitro on murine bone marrow-derived dendritic cells and human dendritic cells. The observed results suggest the consideration of cGAMP as a candidate mucosal adjuvant for human vaccines.

Adjuvant chemotherapy compliance is not superior after thoracoscopic lobectomy

DEFF Research Database (Denmark)

Licht, Peter B; Schytte, Tine; Jakobsen, Erik

2014-01-01

BACKGROUND: It is generally assumed that patient compliance with adjuvant chemotherapy is superior after video-assisted thoracoscopic surgery compared with open lobectomy for non-small cell lung cancer (NSCLC). The level of evidence for this assumption, however, is limited to single-institution, ......BACKGROUND: It is generally assumed that patient compliance with adjuvant chemotherapy is superior after video-assisted thoracoscopic surgery compared with open lobectomy for non-small cell lung cancer (NSCLC). The level of evidence for this assumption, however, is limited to single...... adjuvant chemotherapy and 121 (38.7%) completed all four cycles. Ordinal logistic regression revealed that chemotherapy compliance (none, partial, and full chemotherapy) was significantly reduced by the patient's age (p....02). No significant difference between video-assisted thoracoscopic surgery and thoracotomy was seen regarding chemotherapy compliance (p=0.17), number of chemotherapy cycles (p=0.60), or time from surgery to chemotherapy (p = 0.41). CONCLUSIONS: Complete national data do not support the widespread assumption...

Electrochemical biosensors in pharmaceutical analysis

OpenAIRE

Gil, Eric de Souza; Melo, Giselle Rodrigues de

2010-01-01

Given the increasing demand for practical and low-cost analytical techniques, biosensors have attracted attention for use in the quality analysis of drugs, medicines, and other analytes of interest in the pharmaceutical area. Biosensors allow quantification not only of the active component in pharmaceutical formulations, but also the analysis of degradation products and metabolites in biological fluids. Thus, this article presents a brief review of biosensor use in pharmaceutical analysis, fo...

Modern Vaccines/Adjuvants Formulation--Session 2 (Plenary II): May 15-17, 2013--Lausanne, Switzerland.

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Collin, Nicolas

2013-09-01

On the 15-17th May 2013, the Fourth International Conference on Modern Vaccines/Adjuvants Formulation was organized in Lausanne, Switzerland, and gathered stakeholders from academics and from the industry to discuss several challenges, advances and promises in the field of vaccine adjuvants. Plenary session 2 of the meeting was composed of four different presentations covering: (1) the recent set-up of an adjuvant technology transfer and training platform in Switzerland, (2) the proposition to revisit existing paradigms of modern vaccinology, (3) the properties of polyethyleneimine as potential new vaccine adjuvant, and (4) the progresses in the design of HIV vaccine candidates able to induce broadly neutralizing antibodies.

Assessment of side effects induced by injection of different adjuvant/antigen combinations in rabbits and mice

NARCIS (Netherlands)

Leenaars, P.P.A.M.; Koedam, M.A.; Wester, P.W.; Baumans, V.; Claassen, E.; Hendriksen, C.F.M.

1998-01-01

We evaluated the side effects induced by injection of Freund's adjuvant (FA) and alternative adjuvants combined with different antigens. Rabbits and mice were injected subcutaneously, intramuscularly (rabbits) and intraperitoneally (mice) with different adjuvants (FA, Specol, RIBI, TiterMax,

Adjuvant-enhanced CD4 T Cell Responses are Critical to Durable Vaccine Immunity

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Karen A.O. Martins

2016-01-01

Full Text Available Protein-based vaccines offer a safer alternative to live-attenuated or inactivated vaccines but have limited immunogenicity. The identification of adjuvants that augment immunogenicity, specifically in a manner that is durable and antigen-specific, is therefore critical for advanced development. In this study, we use the filovirus virus-like particle (VLP as a model protein-based vaccine in order to evaluate the impact of four candidate vaccine adjuvants on enhancing long term protection from Ebola virus challenge. Adjuvants tested include poly-ICLC (Hiltonol, MPLA, CpG 2395, and alhydrogel. We compared and contrasted antibody responses, neutralizing antibody responses, effector T cell responses, and T follicular helper (Tfh cell frequencies with each adjuvant's impact on durable protection. We demonstrate that in this system, the most effective adjuvant elicits a Th1-skewed antibody response and strong CD4 T cell responses, including an increase in Tfh frequency. Using immune-deficient animals and adoptive transfer of serum and cells from vaccinated animals into naïve animals, we further demonstrate that serum and CD4 T cells play a critical role in conferring protection within effective vaccination regimens. These studies inform on the requirements of long term immune protection, which can potentially be used to guide screening of clinical-grade adjuvants for vaccine clinical development.

Adjuvant vaginal brachytherapy as a part of management in early endometrial cancer.

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Kellas-Ślęczka, Sylwia; Wojcieszek, Piotr; Białas, Brygida

2012-12-01

Endometrial cancer is the most frequent cancer of female genital tract. Metro- and menorrhagia or postmenopausal bleeding results in its early presentation. It allows radical treatment. However, controversies remain on surgery coverage or adjuvant therapies in early endometrial women cancer. Optimal management should minimize intervention instead of aggressive approach, as showed by recent studies. There is a role for brachytherapy as an adjuvant irradiation. Crucial publications including PORTEC-1, GOG 99, MRC ASTEC, ASTEC/EN.5, PORTEC-2 or Italian lymphadenectomy trial are discussed. Moreover, there is attention paid on adjuvant vaginal brachytherapy analyses for the past fifteen years.

Interferon alpha for the adjuvant treatment of cutaneous melanoma.

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Mocellin, Simone; Lens, Marko B; Pasquali, Sandro; Pilati, Pierluigi; Chiarion Sileni, Vanna

2013-06-18

Interferon alpha is the only agent approved for the postoperative adjuvant treatment of high-risk cutaneous melanoma. However, the survival advantage associated with this treatment is unclear, especially in terms of overall survival. Thus, adjuvant interferon is not universally considered a gold standard treatment by all oncologists. To assess the disease-free survival and overall survival effects of interferon alpha as adjuvant treatment for people with high-risk cutaneous melanoma. We searched the following databases up to August 2012: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2012, issue 8), MEDLINE (from 2005), EMBASE (from 2010), AMED (from 1985), and LILACS (from 1982). We also searched trials databases in 2011, and proceedings of the ASCO annual meeting from 2000 to 2011. We checked the reference lists of selected articles for further references to relevant trials. We included only randomised controlled trials (RCTs) comparing interferon alpha to observation (or any other treatment) for the postoperative (adjuvant) treatment of patients with high-risk skin melanoma, that is, people with regional lymph node metastasis (American Joint Committee on Cancer (AJCC) TNM (tumour, lymph node, metastasis) stage III) undergoing radical lymph node dissection, or people without nodal disease but with primary tumour thickness greater than 1 mm (AJCC TNM stage II). Two authors extracted data, and a third author independently verified the extracted data. The main outcome measure was the hazard ratio (HR), which is the ratio of the risk of the event occurring in the treatment arm (adjuvant interferon) compared to the control arm (no adjuvant interferon). The survival data were either entered directly into Review Manager (RevMan) or extrapolated from Kaplan-Meier plots and then entered into RevMan. Based on the presence of between-study heterogeneity, we applied a fixed-effect or random-effects model for calculating the pooled estimates

Autoimmune/inflammatory syndrome induced by adjuvants (Shoenfeld's syndrome) - An update.

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Watad, A; Quaresma, M; Brown, S; Cohen Tervaert, J W; Rodríguez-Pint, I; Cervera, R; Perricone, C; Shoenfeld, Y

2017-06-01

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) has been widely described in many studies conducted thus far. The syndrome incorporates five immune-mediated conditions, all associated with previous exposure to various agents such as vaccines, silicone implants and several others. The emergence of ASIA syndrome is associated with individual genetic predisposition, for instance those carrying HLA-DRB1*01 or HLA-DRB4 and results from exposure to external or endogenous factors triggering autoimmunity. Such factors have been demonstrated as able to induce autoimmunity in both animal models and humans via a variety of proposed mechanisms. In recent years, physicians have become more aware of the existence of ASIA syndrome and the relationship between adjuvants exposure and autoimmunity and more cases are being reported. Accordingly, we have created a registry that includes at present more than 300 ASIA syndrome cases that have been reported by different physicians worldwide, describing various autoimmune conditions induced by diverse adjuvants. In this review, we have summarized the updated literature on ASIA syndrome and the knowledge accumulated since 2013 in order to elucidate the association between the exposure to various adjuvant agents and its possible clinical manifestations. Furthermore, we especially referred to the relationship between ASIA syndrome and systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS).

Accounting for adjuvant-induced artifacts in the characterization of vaccine formulations by polyacrylamide gel electrophoresis.

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Jakob, Virginie; Brunner, Livia; Barnier-Quer, Christophe; Blust, Molly; Collin, Nicolas; Carter, Lauren; Carter, Darrick; Rausch, Kelly M; Fox, Christopher B

2017-04-01

Several vaccine adjuvants comprise complex nano- or micro-particle formulations, such as oil-in-water emulsions. In order to characterize interactions and compatibility of oil-in-water emulsion adjuvants with protein antigens in vaccines, effective protein characterization methods that can accommodate potential interference from high concentrations of lipid-based particles are needed. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) is a standard protein characterization technique which is affected by the presence of adjuvants such as oil-in-water emulsions. In this article, we investigate variations in SDS-PAGE methods that result in a reduction of adjuvant-induced staining artifacts. We have investigated whether the SDS method or the adjuvant composition were the reason for these artifacts and succeeded in reducing the artifacts with a modified sample preparation and different staining procedures. The best results were obtained by using gold staining or silver staining instead of a Coomassie Blue staining procedure. Moreover, the replacement of the dilution buffer (20% SDS to disrupt emulsion) by alternative detergents such as Tween® 80 and Triton® X-100 removed adjuvant-induced streaking artifacts at the top of the gel. These methods may be useful for improving characterization approaches of antigen-adjuvant mixtures by SDS-PAGE.

APPROACHES TO IMPLEMENTATION OF AN INTEGRATED MANAGEMENT SYSTEM IN THE PHARMACEUTICAL INDUSTRY. GALENICAL PHARMACEUTICAL PRODUCTION

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Ershova Elena Vladimirovna

2015-10-01

Full Text Available This article reviews the issues associated with development of an integrated quality management system and its implementation into a galenical pharmaceutical company. Recently, the Russian pharmaceutical industry has been developing extensively: pharmaceutical clusters are being formed, new and innovative technologies are being developed. For the enterprises producing galenical pharmaceutical products, which feature low prices and a high level of competition, development and implementation of management systems is a way to prove their competitiveness. The purpose of this article is to review the architecture and the key elements of integrated management systems for pharmaceutical enterprises, develop an integrated management system in terms of the upcoming revision of ISO 9001:2015, as well as to describe the benefits of implementation of such systems. The presented approach is the result of an educational project implemented within the framework of the MBA programme in "Master of Business Administration (MBA" in the Federal State Budgetary Educational Institution of Continuing Professional Education Pastukhov State Academy of Industrial Management.

Adjuvant radiotherapy for stage I endometrial cancer.

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Kong, A; Johnson, N; Cornes, P; Simera, I; Collingwood, M; Williams, C; Kitchener, H

2007-04-18

The role of adjuvant radiotherapy (both pelvic external beam radiotherapy and vaginal intracavity brachytherapy) in stage I endometrial cancer following total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH and BSO) remains unclear. To assess the efficacy of adjuvant radiotherapy following surgery for stage I endometrial cancer. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CancerLit, Physician Data Query (PDQ) of National Cancer Institute. Handsearching was also carried out where appropriate. Randomised controlled trials (RCTs) which compared adjuvant radiotherapy versus no radiotherapy following surgery for patients with stage I endometrial cancer were included. Quality of the studies was assessed and data collected using a predefined data collection form. The primary endpoint was overall survival. Secondary endpoints were locoregional recurrence, distant recurrence and endometrial cancer death. Data on quality of life (QOL) and morbidity were also collected. A meta-analysis on included trials was performed using the Cochrane Collaboration Review Manager Software 4.2. The meta-analysis was performed on four trials (1770 patients). The addition of pelvic external beam radiotherapy to surgery reduced locoregional recurrence, a relative risk (RR) of 0.28 (95% confidence interval (CI) 0.17 to 0.44, p ASTEC; Lukka) are awaited. External beam radiotherapy carries a risk of toxicity and should be avoided in stage 1 endometrial cancer patients with no high risk factors.

Pharmaceuticals labelled with stable isotopes

International Nuclear Information System (INIS)

Krumbiegel, P.

1986-11-01

The relatively new field of pharmaceuticals labelled with stable isotopes is reviewed. Scientific, juridical, and ethical questions are discussed concerning the application of these pharmaceuticals in human medicine. 13 C, 15 N, and 2 H are the stable isotopes mainly utilized in metabolic function tests. Methodical contributions are given to the application of 2 H, 13 C, and 15 N pharmaceuticals showing new aspects and different states of development in the field under discussion. (author)

Adjuvant chemotherapy for gastric cancer: Current evidence and future challenges

OpenAIRE

Miceli, Rosalba; Tomasello, Gianluca; Bregni, Giacomo; Di Bartolomeo, Maria; Pietrantonio, Filippo

2014-01-01

Gastric cancer still represents one of the major causes of cancer mortality worldwide. Patients survival is mainly related to stage, with a high proportion of patients with metastatic disease at presentation. Thus, the cure rate largely depend upon surgical resection. Despite the additional, albeit small, benefit of adjuvant chemotherapy has been clearly demonstrated, no general consensus has been reached on the best treatment option. Moreover, the narrow therapeutic index of adjuvant chemoth...

Adjuvant effect in aquaculture fish of cell-wall glycolipids isolated from acid-fast bacteria.

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Matsumoto, Megumi; Araki, Kyosuke; Nishimura, Sayaka; Kuriyama, Hideki; Nakanishi, Teruyuki; Shiozaki, Kazuhiro; Takeuchi, Yutaka; Yamamoto, Atsushi

2018-08-01

Mycobacteriosis and nocardiosis in cultured fish caused by infections with acid-fast bacteria, are responsible for large economic losses globally. In this study, we suggest a novel adjuvant using glycolipids that activates host immune systems. The immune response to glycolipids stimulation was investigated using ginbuna crucian carp. Ginbuna vaccinated with FKC (formalin-killed cells) + glycolipids isolated from Mycobacterium sp., upregulated inflammatory- and Th1-related cytokines, and a DTH (delayed-type hypersensitivity) response was confirmed only in ginbuna vaccinated with FKC + glycolipids. These observations suggest that glycolipids activated host innate and cell-mediated immunity. Subsequently, we evaluated the adjuvant effect of glycolipids against amberjack nocardiosis. In a challenge test, a higher survival rate was observed in amberjack vaccinated with FKC + glycolipids emulsified with conventional oil adjuvant than in fish vaccinated with FKC + oil adjuvant without glycolipids. Therefore, glycolipids potentially could be used as a practical, economical and safe adjuvant for aquaculture fish. Copyright © 2018. Published by Elsevier Ltd.

Interactions and incompatibilities of pharmaceutical excipients with active pharmaceutical ingredients: a comprehensive review

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Sonali S. Bharate

2010-09-01

Full Text Available Studies of active drug/excipient compatibility represent an important phase in the preformulation stage of the development of all dosage forms. The potential physical and chemical interactions between drugs and excipients can affect the chemical nature, the stability and bioavailability of drugs and, consequently, their therapeutic efficacy and safety. The present review covers the literature reports of interaction and incompatibilities of commonly used pharmaceutical excipients with different active pharmaceutical ingredients in solid dosage forms. Examples of active drug/excipient interactions, such as transacylation, the Maillard browning reaction, acid base reactions and physical changes are discussed for different active pharmaceutical ingredients belonging to different therapeutic categories viz antiviral, anti-inflammatory, antidiabetic, antihypertensive, anti-convulsant, antibiotic, bronchodialator, antimalarial, antiemetic, antiamoebic, antipsychotic, antidepressant, anticancer, anticoagulant and sedative/hypnotic drugs and vitamins. Once the solid-state reactions of a pharmaceutical system are understood, the necessary steps can be taken to avoid reactivity and improve the stability of drug substances and products.

The role of adjuvant radiotherapy in the treatment of resectable desmoid tumors

International Nuclear Information System (INIS)

Goy, Barry W.; Lee, Steve P.; Eilber, Frederick; Dorey, Fred; Eckardt, Jeffrey; Fu, Y.-S.; Juillard, Guy J.F.; Selch, Michael T.

1996-01-01

Purpose/Objective: Desmoid tumors have a high propensity for local recurrence with surgical resection. There are many reports describing good responses of desmoid tumors to irradiation, but none have clearly proven the indications for adjuvant radiotherapy in treating resectable desmoid tumors. Materials and Methods: A retrospective analysis was performed on 61 patients with resectable desmoid tumors who were treated at our institution from 1965 to 1992. Fifty-six patients had unifocal disease, of which 34 had positive surgical margins. Forty-five were treated with surgery alone, while 11 received surgery plus adjuvant radiotherapy. Median follow-up was 6 years. Local control was measured from the last day of treatment, and all cases were reviewed by our Department of Pathology. Results: Univariate analysis of 56 patients with unifocal disease revealed that female gender (p=0.025) and positive margins (p=0.032) predicted for local recurrence. Multivariate analysis revealed that only positive margins (p=0.003) independently predicted for local recurrence. Only 3 of 22 patients had local recurrences with clear margins, with a 6 year actuarial local control of 85%. We analyzed 34 patients with positive margins by univariate analysis, and only adjuvant radiotherapy predicted for improved local control (p=0.031). Multivariate analysis of these 34 patients revealed that adjuvant radiotherapy independently predicted for local control (p=0.012), and patients with recurrent disease had a slightly higher risk of local recurrence (p=0.083). The 6 year actuarial local control determined by Kaplan-Meier for patients with unifocal disease and positive margins was 32%(±12%) with surgery alone, and 78%(±14%) with surgery plus adjuvant radiotherapy (p=0.019). None of the patients who received radiotherapy for unifocal disease developed serious complications, or a secondary malignancy. Conclusions: Adjuvant radiotherapy is indicated in the treatment of patients with resectable

Pharmaceutical virtue.

Science.gov (United States)

Martin, Emily

2006-06-01

In the early history of psychopharmacology, the prospect of developing technologically sophisticated drugs to alleviate human ills was surrounded with a fervor that could be described as religious. This paper explores the subsequent history of the development of psychopharmacological agents, focusing on the ambivalent position of both the industry and its employees. Based on interviews with retired pharmaceutical employees who were active in the industry in the 1950s and 1960s when the major breakthroughs were made in the development of MAOIs and SSRIs, the paper explores the initial development of educational materials for use in sales campaigns. In addition, based on interviews with current employees in pharmaceutical sales and marketing, the paper describes the complex perspective of contemporary pharmaceutical employees who must live surrounded by the growing public vilification of the industry as rapacious and profit hungry and yet find ways to make their jobs meaningful and dignified. The paper will contribute to the understudied problem of how individuals function in positions that require them to be part of processes that on one description constitute a social evil, but on another, constitute a social good.

[PICS: pharmaceutical inspection cooperation scheme].

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Morénas, J

2009-01-01

The pharmaceutical inspection cooperation scheme (PICS) is a structure containing 34 participating authorities located worldwide (October 2008). It has been created in 1995 on the basis of the pharmaceutical inspection convention (PIC) settled by the European free trade association (EFTA) in1970. This scheme has different goals as to be an international recognised body in the field of good manufacturing practices (GMP), for training inspectors (by the way of an annual seminar and experts circles related notably to active pharmaceutical ingredients [API], quality risk management, computerized systems, useful for the writing of inspection's aide-memoires). PICS is also leading to high standards for GMP inspectorates (through regular crossed audits) and being a room for exchanges on technical matters between inspectors but also between inspectors and pharmaceutical industry.

Recognizing misleading pharmaceutical marketing online.

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De Freitas, Julian; Falls, Brian A; Haque, Omar S; Bursztajn, Harold J

2014-01-01

In light of decision-making psychology, this article details how drug marketing operates across established and novel web domains and identifies some common misleading trends and influences on prescribing and patient-initiated medication requests. The Internet has allowed pharmaceutical marketing to become more salient than ever before. Although the Internet's growth has improved the dissemination of pharmaceutical information, it has also led to the increased influence of misleading pharmaceutical marketing. Such mismarketing is of concern, especially in psychiatry, since psychotropics generate considerable revenue for drug companies. In a climate of resource-limited drug regulation and time-strapped physicians, we recommend improving both independent monitoring and consumer awareness of Internet-enabled, potentially misleading, pharmaceutical marketing influences. © 2014 American Academy of Psychiatry and the Law.

Forging a potent vaccine adjuvant: CpG ODN/cationic peptide nanorings.

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Gungor, Bilgi; Yagci, Fuat Cem; Gursel, Ihsan; Gursel, Mayda

Type I interferon inducers may potentially be engineered to function as antiviral and anticancer agents, or alternatively, vaccine adjuvants, all of which may have clinical applications. We recently described a simple strategy to convert a Toll-like receptor 9 (TLR9) agonist devoid of interferon α (IFNα) stimulating activity into a robust Type I interferon inducer with potent vaccine adjuvant activity.

Natural and synthetic saponin adjuvant QS-21 for vaccines against cancer

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Ragupathi, Govind; Gardner, Jeffrey R; Livingston, Philip O; Gin, David Y

2013-01-01

One of the most widely used and potent immunological adjuvants is a mixture of soluble triterpene glycosides purified from the soap bark tree (Quillaja saponaria). Despite challenges in production, quality control, stability and toxicity, the QS-21 fraction from this extract has exhibited exceptional adjuvant properties for a range of antigens. It possesses an ability to augment clinically significant antibody and T-cell responses to vaccine antigens against a variety of infectious diseases, degenerative disorders and cancers. The recent synthesis of active molecules of QS-21 has provided a robust method to produce this leading vaccine adjuvant in high purity as well as to produce novel synthetic QS-21 congeners designed to induce increased immune responsiveness and decreased toxicity. PMID:21506644

Combined-modality treatment in advanced oral squamous cell carcinoma. Primary surgery followed by adjuvant concomitant radiochemotherapy

International Nuclear Information System (INIS)

Kreppel, Matthias; Dreiseidler, Timo; Zoeller, Joachim E.; Scheer, Martin; Drebber, Uta; Eich, Hans-Theodor; Mueller, Rolf-Peter

2011-01-01

The efficacy of adjuvant radiochemotherapy (RCT) in patients with advanced stage head and neck carcinoma has been proven in prospective randomized trials. However, these trials focused on different head and neck sites. Specific analyses for treatment effects in squamous cell carcinoma of the oral cavity (OSCC) are missing. We evaluated our experiences with adjuvant concomitant RCT in advanced OSCC to compare the results with other treatment schemes using adjuvant RCT. A total of 183 patients with OSCC of UICC stages II-IVb were reviewed retrospectively. All patients were treated with radical surgery followed by adjuvant, conventional fractionated concomitant RCT using carboplatin. Overall survival was plotted by Kaplan-Meier analysis. Prognostic factors were identified through univariate and multivariate analysis. Univariate analysis showed a significant impact of T, N, and UICC stage, histopathologic grading, surgical margins, extracapsular spread (ECS), and lymphangiosis carcinomatosa on overall survival (Table 3). Patients with stage IVa had a higher 5-year overall survival rate (42.8%) than patients with stage IVb (25.0%) (Figure 1). The differences were significant in multivariate analysis (p = 0.033) (Table 4). Adjuvant concomitant RCT is an effective treatment in patients with advanced stage OSCC. However, it remains unclear, which patients should be treated with adjuvant RCT. For patients with stage IVb, adjuvant RCT yields poor results. Prospective randomized trials are needed to confirm which patients should be treated with adjuvant RCT. (orig.)

Nomogram for Predicting the Benefit of Adjuvant Chemoradiotherapy for Resected Gallbladder Cancer

Science.gov (United States)

Wang, Samuel J.; Lemieux, Andrew; Kalpathy-Cramer, Jayashree; Ord, Celine B.; Walker, Gary V.; Fuller, C. David; Kim, Jong-Sung; Thomas, Charles R.

2011-01-01

Purpose Although adjuvant chemoradiotherapy for resected gallbladder cancer may improve survival for some patients, identifying which patients will benefit remains challenging because of the rarity of this disease. The specific aim of this study was to create a decision aid to help make individualized estimates of the potential survival benefit of adjuvant chemoradiotherapy for patients with resected gallbladder cancer. Methods Patients with resected gallbladder cancer were selected from the Surveillance, Epidemiology, and End Results (SEER) –Medicare database who were diagnosed between 1995 and 2005. Covariates included age, race, sex, stage, and receipt of adjuvant chemotherapy or chemoradiotherapy (CRT). Propensity score weighting was used to balance covariates between treated and untreated groups. Several types of multivariate survival regression models were constructed and compared, including Cox proportional hazards, Weibull, exponential, log-logistic, and lognormal models. Model performance was compared using the Akaike information criterion. The primary end point was overall survival with or without adjuvant chemotherapy or CRT. Results A total of 1,137 patients met the inclusion criteria for the study. The lognormal survival model showed the best performance. A Web browser–based nomogram was built from this model to make individualized estimates of survival. The model predicts that certain subsets of patients with at least T2 or N1 disease will gain a survival benefit from adjuvant CRT, and the magnitude of benefit for an individual patient can vary. Conclusion A nomogram built from a parametric survival model from the SEER-Medicare database can be used as a decision aid to predict which gallbladder patients may benefit from adjuvant CRT. PMID:22067404

Pharmaceutical care in Kuwait: hospital pharmacists' perspectives.

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Katoue, Maram G; Awad, Abdelmoneim I; Schwinghammer, Terry L; Kombian, Samuel B

2014-12-01

Pharmaceutical care practice has been championed as the primary mission of the pharmacy profession, but its implementation has been suboptimal in many developing countries including Kuwait. Pharmacists must have sufficient knowledge, skills, and positive attitudes to practise pharmaceutical care, and barriers in the pharmacy practice model must be overcome before pharmaceutical care can be broadly implemented in a given healthcare system. To investigate hospital pharmacists' attitudes towards pharmaceutical care, perceptions of their preparedness to provide pharmaceutical care, and the barriers to its implementation in Kuwait. Six general hospitals, eight specialized hospitals and seven specialized health centers in Kuwait. A descriptive, cross-sectional survey was distributed to all pharmacists working in the governmental hospitals in Kuwait (385 pharmacists). Data were collected via a pre-tested self-administered questionnaire. Descriptive statistics including percentages, medians and means Likert scale rating (standard deviations) were calculated and compared using statistical package for social sciences, version 20. Statistical significance was accepted at a p value of Kuwait. Completed surveys were received from 250 (64.9%) of the 385 pharmacists. Pharmacists expressed overall positive attitudes towards pharmaceutical care. They felt well prepared to implement the various aspects of pharmaceutical care, with the least preparedness in the administrative/management aspects. Pharmacists with more practice experience expressed significantly more positive attitudes towards pharmaceutical care (p = 0.001) and they felt better prepared to provide pharmaceutical care competencies (p Kuwait advocate implementation of pharmaceutical care while also appreciating the organizational, technical and professional barriers to its widespread adoption. Collaborative efforts between health authorities and educational institutions, and the integration of innovative approaches in

Benefit of adjuvant chemotherapy in patients with T4 UICC II colon cancer

International Nuclear Information System (INIS)

Teufel, Andreas; Gerken, Michael; Hartl, Janine; Itzel, Timo; Fichtner-Feigl, Stefan; Stroszczynski, Christian; Schlitt, Hans Jürgen; Hofstädter, Ferdinand; Klinkhammer-Schalke, Monika

2015-01-01

Colorectal cancer is the third most common cancer and a major cause of morbidity and mortality worldwide. Adjuvant chemotherapy is considered the standard of care in patients with UICC stage III colon cancer after R0 resection. Adjuvant therapy was not shown to be beneficial in patients with UICC stage II colon cancer. However, there is an ongoing discussion as to whether adjuvant chemotherapy may be beneficial for a subgroup of UICC II patients in a “high-risk situation” (such as T4). We investigated a Bavarian population-based (2.1 million inhabitants) cohort of 1937 patients with UICC II CRC treated between 2002 and 2012 in regard of the benefit of adjuvant chemotherapy for large (T4) tumors. Patients older than 80 years of age were excluded. Of 1937 patients, 240 had a T4 tumor (12 %); 77 of all T4 patients received postoperative chemotherapy (33 %). Kaplan-Meier analysis and Cox regression models were used for survival analyses. Patients with a T4 tumor who received postoperative chemotherapy had a highly significant survival benefit in respect of overall survival (p < 0.001) and recurrence-free survival (p = 0.008). However, no difference was observed between oxaliplatin-containing and non-oxaliplatin-containing treatment regimens. G2 and G3 tumors were found to particularly benefit from adjuvant treatment. Chemotherapy, age at diagnosis, and tumor grading remained independent risk factors in the multivariate cox regression analysis. Our retrospective study demonstrated the significant benefit of adjuvant chemotherapy in the T4 subgroup of patients with UICC II colon cancer. Our data suggest that adjuvant chemotherapy should be seriously considered in these patients. The online version of this article (doi:10.1186/s12885-015-1404-9) contains supplementary material, which is available to authorized users

Successful adjuvant-free vaccination of BALB/c mice with mutated amyloid β peptides

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Wahi Monika M

2008-02-01

Full Text Available Abstract Background A recent human clinical trial of an Alzheimer's disease (AD vaccine using amyloid beta (Aβ 1–42 plus QS-21 adjuvant produced some positive results, but was halted due to meningoencephalitis in some participants. The development of a vaccine with mutant Aβ peptides that avoids the use of an adjuvant may result in an effective and safer human vaccine. Results All peptides tested showed high antibody responses, were long-lasting, and demonstrated good memory response. Epitope mapping indicated that peptide mutation did not lead to epitope switching. Mutant peptides induced different inflammation responses as evidenced by cytokine profiles. Ig isotyping indicated that adjuvant-free vaccination with peptides drove an adequate Th2 response. All anti-sera from vaccinated mice cross-reacted with human Aβ in APP/PS1 transgenic mouse brain tissue. Conclusion Our study demonstrated that an adjuvant-free vaccine with different Aβ peptides can be an effective and safe vaccination approach against AD. This study represents the first report of adjuvant-free vaccines utilizing Aβ peptides carrying diverse mutations in the T-cell epitope. These largely positive results provide encouragement for the future of the development of human vaccinations for AD.

Timing of adjuvant chemotherapy and its relation to survival among patients with stage III colon cancer.

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Bos, A C R K; van Erning, F N; van Gestel, Y R B M; Creemers, G J M; Punt, C J A; van Oijen, M G H; Lemmens, V E P P

2015-11-01

Currently available data suggest that delaying the start of adjuvant chemotherapy in colon cancer patients has a detrimental effect on survival. We analysed which factors impact on the timing of adjuvant chemotherapy and evaluated the influence on overall survival (OS). Stage III colon cancer patients who underwent resection and received adjuvant chemotherapy between 2008 and 2013 were selected from the Netherlands Cancer Registry. Timing of adjuvant chemotherapy was subdivided into: ⩽ 4, 5-6, 7-8, 9-10, 11-12 and 13-16 weeks post-surgery. Multivariable regressions were performed to assess the influence of several factors on the probability of starting treatment within 8 weeks post-surgery and to evaluate the association of timing of adjuvant chemotherapy with 5-year OS. 6620 patients received adjuvant chemotherapy, 14% commenced after 8 weeks. Factors associated with starting treatment after 8 weeks were older age (Odds ratio (OR) 65-74 versus colon cancer patients within 8 weeks post-surgery. Copyright © 2015 Elsevier Ltd. All rights reserved.

Antinociceptive effect of chlorphenesin carbamate in adjuvant arthritic rats.

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Okuyama, S; Aihara, H

1987-02-01

The antinociceptive effect of chlorphenesin carbamate (CPC) and mephenesin were examined in adjuvant arthritic rats. In the behavioral study, CPC (100-400 mg/kg, p.o.) but not mephenesin (100-400 mg/kg, p.o.) had a dose-dependent antinociceptive effect, determined using the flexion test. In the electrophysiological study, CPC (25-50 mg/kg, i.v.) but not mephenesin (50 mg/kg, i.v.) depressed the evoked neuronal responses of nociceptive neurons in the ventrobasal thalamus (VB), while the evoked responses of non-nociceptive neurons were not depressed by either CPC (50 mg/kg, i.v.) or mephenesin (50 mg/kg, i.v.). The spontaneous firings of the VB nociceptive neurons were depressed by both CPC (50 mg/kg, i.v.) and mephenesin (50 mg/kg, i.v.). However, mephenesin (50 mg/kg, i.v.) but not CPC (50 mg/kg, i.v.) also depressed the spontaneous firings of the mesencephalic reticular formation (RF), in these adjuvant arthritic rats. These results indicate that CPC but not mephenesin, has an antinociceptive action in adjuvant arthritic rats.

Tocotrienols are good adjuvants for developing cancer vaccines

International Nuclear Information System (INIS)

Abdul Hafid, Sitti Rahma; Radhakrishnan, Ammu Kutty; Nesaretnam, Kalanithi

2010-01-01

Dendritic cells (DCs) have the potential for cancer immunotherapy due to their ability to process and present antigens to T-cells and also in stimulating immune responses. However, DC-based vaccines have only exhibited minimal effectiveness against established tumours in mice and humans. The use of appropriate adjuvant enhances the efficacy of DC based cancer vaccines in treating tumours. In this study we have used tocotrienol-rich fraction (TRF), a non-toxic natural compound, as an adjuvant to enhance the effectiveness of DC vaccines in treating mouse mammary cancers. In the mouse model, six-week-old female BALB/c mice were injected subcutaneously with DC and supplemented with oral TRF daily (DC+TRF) and DC pulsed with tumour lysate from 4T1 cells (DC+TL). Experimental mice were also injected with DC pulsed with tumour lysate and supplemented daily with oral TRF (DC+TL+TRF) while two groups of animal which were supplemented daily with carrier oil (control) and with TRF (TRF). After three times vaccination, mice were inoculated with 4T1 cells in the mammary breast pad to induce tumour. Our study showed that TRF in combination with DC pulsed with tumour lysate (DC+TL+TRF) injected subcutaneously significantly inhibited the growth of 4T1 mammary tumour cells as compared to control group. Analysis of cytokines production from murine splenocytes showed significant increased productions of IFN-γ and IL-12 in experimental mice (DC+TL+TRF) compared to control, mice injected with DC without TRF, mice injected with DC pulsed with tumour lysate and mice supplemented with TRF alone. Higher numbers of cytotoxic T cells (CD8) and natural killer cells (NK) were observed in the peripheral blood of TRF adjuvanted DC pulsed tumour lysate mice. Our study show that TRF has the potential to be an adjuvant to augment DC based immunotherapy

Adjuvant endocrine and chemotherapy for early breast cancer

International Nuclear Information System (INIS)

Henderson, I. Craig

1996-01-01

Objective: Present the results of the 1995 World Overview which will be held in Oxford England two weeks before ASTRO. Discuss the interpretation and application of these results. Review current research topics on the use of adjuvant endocrine and chemotherapy for early breast cancer. The survival benefits from adjuvant chemotherapy in premenopausal women and adjuvant tamoxifen in postmenopausal women are well established. Each will reduce the annual odds of death by about 25% resulting in a 10 year survival difference of 8-10%. By the time of this presentation, the results of the 1995 Adjuvant Therapy Overview should be with 10+ years of follow-up, and if possible these will be summarized. Current efforts to improve on previous results are focused on the following areas: Optimal chemotherapy dose. Decreasing dose will compromise patient survival. It is not as certain that increasing dose will have as much impact in improving survival. The NSABP was unable to demonstrate an improvement in survival by modestly increasing the dose of cyclophosphamide alone. However, recent results of a Canadian study of CEF (cyclophosphamide, epidoxorubicin, and 5-fluorouracil) and an Intergroup trial of an intense 16 week polychemotherapy program keep alive the possibility that dose escalation is still a very important question. An NSABP trial evaluating even greater cyclophosphamide dose escalation, an Intergroup evaluation of different doxorubicin doses, and two Intergroup trials evaluating very high dose chemotherapy and bone marrow transplantation should provide definitive evidence regarding the importance of dose. Drug sequence. A study from Milan suggests that initial treatment with single agent doxorubicin followed by CMF will be superior to alternating doxorubicin and CMF. This has not been confirmed yet, and the reason for increased benefit from such a sequence is not entirely clear. This concept is being explored further in an Intergroup trial comparing four cycles of

Prognostic significance of adjuvant radiation therapy in adenocarcinoma of the cecum

Science.gov (United States)

Hosseini, Sare; Bananzadeh, Ali Mohammad; Mohammadianpanah, Mohammad; Salek, Roham; Taghizadeh-Kermani, Ali

2018-01-01

Purpose Local recurrence is a common failure pattern in adenocarcinoma of the cecum. This study aimed to investigate the potential role of adjuvant radiation therapy on oncologic outcomes of patients with adenocarcinoma of the cecum. Materials and Methods This retrospective study was carried out at three large tertiary university hospitals. We analyzed the characteristics, prognostic factors, and survival of 162 patients with adenocarcinoma of the cecum that were treated and followed up between 2000 and 2013. All the patients had undergone a right hemicolectomy and received chemotherapy with (n = 48) or without (n = 114) adjuvant radiation therapy. Results The subjects were 65 females and 97 males with a median age of 56 years (range, 17 to 90 years) at diagnosis. The 5-year local control (LC), disease free survival (DFS), and overall survival (OS) rates were 72.7%, 57.2%, and 62.6% respectively. In a multivariate analysis, age, tumor stage, node stage, and adjuvant radiation therapy were determined to be independent prognostic factors. Age more than 55 years (hazard ratio [HR] = 1.0; 95% confidence interval [CI], 0.06–0.32; p = 0.003], T4 stage (HR = 6.8; 95% CI, 3.07–15.36; p < 0.001), node positive disease (HR = 4.2; 95% CI, 1.94–9.13; p < 0.001), and the absence of adjuvant radiation therapy (HR = 3.0; 95% CI, 1.39–6.46; p = 0.005) had a negative influence on OS. Conclusion Adjuvant radiation therapy significantly improves DFS and OS in patients with adenocarcinoma of the cecum. PMID:29506326

The identification of plant lectins with mucosal adjuvant activity

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Lavelle, E C; Grant, G; Pusztai, A; Pfüller, U; O'hagan, D T

2001-01-01

To date, the most potent mucosal vaccine adjuvants to be identified have been bacterial toxins. The present data demonstrate that the type 2 ribosome-inactivating protein (type 2 RIP), mistletoe lectin I (ML-I) is a strong mucosal adjuvant of plant origin. A number of plant lectins were investigated as intranasal (i.n.) coadjuvants for a bystander protein, ovalbumin (OVA). As a positive control, a potent mucosal adjuvant, cholera toxin (CT), was used. Co-administration of ML-I or CT with OVA stimulated high titres of OVA-specific serum immunoglobulin G (IgG) in addition to OVA-specific IgA in mucosal secretions. CT and ML-I were also strongly immunogenic, inducing high titres of specific serum IgG and specific IgA at mucosal sites. None of the other plant lectins investigated significantly boosted the response to co-administered OVA. Immunization with phytohaemagglutinin (PHA) plus OVA elicited a lectin-specific response but did not stimulate an enhanced response to OVA compared with the antigen alone. Intranasal delivery of tomato lectin (LEA) elicited a strong lectin-specific systemic and mucosal antibody response but only weakly potentiated the response to co-delivered OVA. In contrast, administration of wheatgerm agglutinin (WGA) or Ulex europaeus lectin 1 (UEA-I) with OVA stimulated a serum IgG response to OVA while the lectin-specific responses (particularly for WGA) were relatively low. Thus, there was not a direct correlation between immunogenicity and adjuvanticity although the strongest adjuvants (CT, ML-I) were also highly immunogenic. PMID:11168640

The role of cocrystals in pharmaceutical science.

Science.gov (United States)

Shan, Ning; Zaworotko, Michael J

2008-05-01

Pharmaceutical cocrystals, a subset of a long known but little-studied class of compounds, represent an emerging class of crystal forms in the context of pharmaceutical science. They are attractive to pharmaceutical scientists because they can significantly diversify the number of crystal forms that exist for a particular active pharmaceutical ingredient (API), and they can lead to improvements in physical properties of clinical relevance. In this article we address pharmaceutical cocrystals from the perspective of design (crystal engineering) and present a series of case studies that demonstrate how they can enhance the solubility, bioavailability, and/or stability of API crystal forms.

Entrepreneurial patent management in pharmaceutical startups.

Science.gov (United States)

Holgersson, Marcus; Phan, Tai; Hedner, Thomas

2016-07-01

Startups fill an increasingly important role as innovators in the pharmaceutical industry, and patenting is typically central to their success. This article aims to explore patent management in pharmaceutical startups. The results show that startups need to deal with several challenges related to patenting and an 'entrepreneurial' approach to patent management is called for. Resource constraints, venture capital provision, exits and other conditions and events must be readily considered in the patent management process to build a successful pharmaceutical venture, something that could benefit the pharmaceutical industry as a whole. Copyright © 2016 Elsevier Ltd. All rights reserved.

Introduction: Institutional corruption and the pharmaceutical policy.

Science.gov (United States)

Rodwin, Marc A

2013-01-01

Today, the goals of pharmaceutical policy and medical practice are often undermined due to institutional corruption - that is, widespread or systemic practices, usually legal, that undermine an institution's objectives or integrity. In this symposium, 16 articles investigate the corruption of pharmaceutical policy, each taking a different look at the sources of corruption, how it occurs, and what is corrupted. We will see that the pharmaceutical industry's own purposes are often undermined. Furthermore, pharmaceutical industry funding of election campaigns and lobbying skews the legislative process that sets pharmaceutical policy. Moreover, certain practices have corrupted medical research, the production of medical knowledge, the practice of medicine, drug safety, the Food and Drug Administration's oversight of the pharmaceutical market, and the trustworthiness of patient advocacy organizations. © 2013 American Society of Law, Medicine & Ethics, Inc.

Antigen-Sparing and Enhanced Efficacy of Multivalent Vaccines Adjuvanted with Immunopotentiators in Chickens

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Peipei Wu

2017-05-01

Full Text Available We previously described that immunopotentiators, CVCVA5, increased the efficacy of H5 and H9 subtype avian influenza vaccines in chickens, ducks, and geese. In this study, we further investigated the effects of the CVCVA5 for improving the efficacy of other univalent or multivalent inactivated vaccines. The immune response administrated with half-dose of monovalent vaccine plus CVCVA5 were higher than those of one dose of monovalent vaccine without immunopotentiators as measured by levels of antibodies from serum, tears and bronchoalveolar lavage fluids, and cytokines of IFNγ and IL-4 from serum. Vaccines included the univalent vaccine of Newcastle Disease virus (ND, Egg Drop Syndrome virus (EDS, Infectious Bronchitis virus (IB, and Infectious Bursal Disease virus (IBD. The CVCVA5 also improved the immune response of both ND and IBD vaccines with less dosage. The sterile protective immunity was monitored with one- or a half-dose of adjuvanted ND vaccine or one dose of adjuvanted IBD vaccine, respectively. The improved immune efficacy was observed in a half-dose of adjuvanted bivalent vaccines compared to one dose of vaccines without CVCVA5 as measured by the antibody levels, including bivalent vaccine of ND-H9, ND-IB, and ND-IBD. The CVCVA5 also boosted the immune efficacy of the tetravalent vaccine (ND-IB-EDS-H9. A half-dose of adjuvanted commercial vaccine or 75% antigen-sparing adjuvanted vaccine elicited similar antibody levels to those of one dose non-adjuvanted commercial vaccines. The CVCVA5 improved the effect of a booster vaccination as measured by the antibody levels against H5 or H9 virus antigens, in which chickens primed with the adjuvanted ND-IB vaccines given a booster with H5–H9 bivalent vaccines without CVCVA5 using 5-day intervals. The inflammatory response may contribute to these additional effects by increasing the levels of IFNγ and IL-4 after the injection of the adjuvanted ND-IB vaccines. Results indicated that the

Oncoplastic breast surgery does not delay the onset of adjuvant chemotherapy

DEFF Research Database (Denmark)

Klit, Anders; Tvedskov, Tove Filtenborg; Kroman, Niels

2017-01-01

BACKGROUND: Only a few studies of limited size have examined whether oncoplastic breast surgery delays the onset of adjuvant chemotherapy as compared to conventional breast surgery. We investigated whether oncoplastic breast surgery causes a delay in the onset of adjuvant chemotherapy in comparison...... to lumpectomy and mastectomy. MATERIAL AND METHODS: The study is a population-based cohort study. Within the nationwide registry of the Danish Breast Cancer Group (DBCG), we identified 1798 patients who received adjuvant chemotherapy following mastectomy, lumpectomy or oncoplastic breast surgery for early...... and unilateral invasive breast cancer. Women treated with neoadjuvant chemotherapy were excluded. RESULTS: We found no significant difference between the three groups (mastectomy, lumpectomy, oncoplastic breast surgery) in the time from biopsy to surgery (mean time 17.9, 17.0 and 18.3 days, respectively...

Integrating systems Approaches into Pharmaceutical Sciences

DEFF Research Database (Denmark)

Westerhoff, H.V.; Mosekilde, Erik; Noe, C. R.

2008-01-01

During the first week of December 2007, the European Federation for Pharmaceutical Sciences (EUFEPS) and BioSim, the major European Network of Excellence on Systems Biology, held a challenging conference on the use of mathematical models in the drug development process. More precisely, the purpose...... of the conference was to promote the ‘Integration of Systems Approaches into Pharmaceutical Sciences’ in view of optimising the development of new effective drugs. And a challenge this is, considering both the high attrition rates in the pharmaceutical industry and the failure of finding definitive drug solutions...... for many of the diseases that plague mankind today. The conference was co-sponsored by the American College of Clinical Pharmacology, the European Center for Pharmaceutical Medicine, and the Swiss Society of Pharmaceutical Sciences and, besides representatives from the European Regulatory Agencies and FDA...

Impact of adjuvant chemotherapy for gliomatosis cerebri

International Nuclear Information System (INIS)

Kong, Doo-Sik; Nam, Do-Hyun; Kim, Sung Tae; Lee, Jung-Il; Suh, Yeon-Lim; Lim, Do Hoon; Kim, Won Seog; Kwon, Ki-Hoon; Park, Kwan; Kim, Jong Hyun

2010-01-01

Gliomatosis cerebri (GC) is characterized by a diffuse infiltration of tumor cells throughout CNS, however, few details are available about the chemotherapeutic effect on GC. The aim of this study was to investigate its clinical course and to determine the efficacy of chemotherapy for GC. Between Jan. 1999 and Dec. 2004, 37 GC patients were diagnosed by biopsy and treated with radiotherapy in a single institution. To determine the efficacy of chemotherapy for GC, we retrospectively reviewed their clinical courses. The study cohort was divided into 2 groups, those with and without receiving post-radiotherapy adjuvant chemotherapy such as temozolomide or nitrosourea-based chemotherapy. Nineteen patients with adjuvant chemotherapy were assigned to the chemotreatment group and 18 with radiotherapy alone were assigned to the control group. Mean survival for chemotreatment group and control group were 24.2 and 13.1 months, respectively (p = 0.045). Time to progression for these groups were 16.0 and 6.0 months, respectively (p = 0.007). Overall review of the clinical course of patients with GC provided that early appearance of new contrast-enhancing lesions within 6 months from the initial diagnosis and higher histological grade were closely associated with poor survival (p < 0.001 and p = 0.008). Adjuvant chemotherapy following radiotherapy could prolong the survival in patients with GC. In addition, newly developed contrast-enhanced lesions on the follow-up MR images indicate the progression of GC

The Effectiveness of Pharmaceutical Marketing

NARCIS (Netherlands)

E.R. Kappe

2011-01-01

textabstractPharmaceutical marketing effectiveness comprises the measurement of marketing efforts of pharmaceutical firms towards doctors and patients. These firms spend billions of dollars yearly to promote their prescription drugs. This dissertation provides empirical analyses and methods to

ANALYSIS OF SCIENTIFIC RESEARCHES IN PHARMACEUTICAL PROMOTION GLOBALLY: TOWARDS INTERNATIONALLY DEVELOPING PRACTICALLY-ORIENTED GUIDELINES FOR PHARMACEUTICAL COMPANIES

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M. M. Bahlol

2016-01-01

Full Text Available Purpose. Pharmaceutical industry is transnational and globally important. Many pharmaceutical companies operate their business in multinational and international forms in different countries. Diverse researches from different countries indicated and confirmed marketing promotion importance in pharmaceutical field. Therefore, marketing promotion and its effects are a very important issue that should be globally investigated in real life and evidence context. We oriented our research according to these scientific and practical values.Methodology. We reviewed pharmaceutical marketing promotion researches from more than 25 different countries, e.g., USA, Canada, Italy, France, Russia, India, Egypt and Syria where we employed our knowledge of three widely spread languages, i.e., English, Russian and Arabic. Such language variation supports us with large and variable amount of scientific knowledge, deep understanding and ability of analysis. Some studies investigated average response to pharmaceutical marketing promotion and few studies took into consideration heterogeneity in their effects with respect to advertising medium or drug characteristics.Originality. We investigated empirical evidences of pharmaceutical marketing promotion that can be directed to either consumer or healthcare professionals.Findings. We extracted, gathered and associated information of pharmaceutical promotion globally which oriented us to several evidence and practical facts with regard to employing promotion tools in different definite situations pertinent to main directions; their welfare and health enhancing effects and adverse effects. Practical Implications- Consequently, we developed practically-oriented guidelines for companies concerning pharmaceutical promotion globally ate the end of this paper.

Neoadjuvant chemoradiation (modified Eilber protocol) versus adjuvant radiotherapy in the treatment of extremity soft tissue sarcoma

International Nuclear Information System (INIS)

Lehane, Chris; Parasyn, Andrew; Ho, Frederick; Thompson, Stephen R.; Smee, Robert; Links, David; Crowe, Phil; Lewis, Craig; Friedlander, Michael; Williams, Janet

2016-01-01

Local control for extremity soft tissue sarcomas (STS) requires surgery combined with radiotherapy, usually given pre-operatively or post-operatively. The modified Eilber protocol, a neoadjuvant chemoradiation regimen, has been reported with excellent local control rates. This retrospective single-centre study compared outcomes for patients treated with the modified Eilber protocol with those treated with standard adjuvant radiotherapy. Twenty-nine patients were treated with modified Eilber protocol. Thirty-four patients received adjuvant radiotherapy. Three patients (10%) in the Eilber group and five patients (15%) in the Adjuvant group developed local recurrence (P = 0.87). Major acute wound complications were noted in four patients in each group (P = 0.55). One patient (3.4%) in the Eilber group developed Grade 3 or 4 late toxicities after 1 year compared with nine patients (27%) in the Adjuvant group (P = 0.02). Patients with a diagnosis of extremity STS were retrospectively reviewed from the Prince of Wales Hospital Sarcoma Database from 1995 to 2012. Sixty-three patients underwent curative surgery with either neoadjuvant Eilber chemoradiotherapy (Eilber) or adjuvant radiotherapy (Adjuvant). Neoadjuvant chemoradiation (Eilber protocol) provided similar rates of local control when compared with adjuvant radiotherapy. Acute wound complication rates were similar but there was less severe late toxicity in the Eilber group.

[Bioequivalence studies of pharmaceutical preparations].

Science.gov (United States)

Vetchý, D; Frýbortová, K; Rabisková, M; Danecková, H

2007-01-01

Bioequivalence studies are very important for the development of a pharmaceutical preparation in the pharmaceutical industry. Their rationale is the monitoring of pharmacokinetic and pharmacodynamic parameters after the administration of tested drugs. The target of such study is to evaluate the therapeutic compatibility of tested drugs (pharmaceutical equivalents or pharmaceutical alternatives). The importance of bioequivalence studies is increasing also due to the large growth of the production and consumption of generic products. Generic products represent approximately 50 % of the whole consumption in many European countries and USA. The search output of bioequivalence study is together with the pharmaceutical quality data of medical product one of the main part of the registration file submitted to a national regulatory authorities. The registration of generic products does not demand complicated and expensive clinical study contrary to original product. The comparison of the original and the generic product via bioequivalence study is suggested as sufficient. The aim of this article is to provide to a medical public a summary about the types of bioequivalence studies, their range, rules of their practise and let them gain their own attitude to this question.

Carbohydrate fatty acid monosulphate esters are safe and effective adjuvants for humoral responses.

Science.gov (United States)

Hilgers, Luuk A Th; Platenburg, Peter Paul L I; Bajramovic, Jeffrey; Veth, Jennifer; Sauerwein, Robert; Roeffen, Will; Pohl, Marie; van Amerongen, Geert; Stittelaar, Koert J; van den Bosch, Johannes F

2017-05-31

Carbohydrate fatty acid sulphate esters (CFASEs) formulated in a squalane-in-water emulsion are effective adjuvants for humoral responses to a wide range of antigens in various animal species but rise in body temperature and local reactions albeit mild or minimal hampers application in humans. In rabbits, body temperature increased 1°C one day after intramuscular (IM) injection, which returned to normal during the next day. The effect increased with increasing dose of CFASE but not with the number of injections (up to 5). Antigen enhanced the rise in body temperature after booster immunization (P100-fold after the second immunization. In ferrets immunized with 7.5μg of inactivated influenza virus A/H7N9, CMS adjuvant gave 100-fold increase in HAI antibody titres after the first and 25-fold after the second immunisation, which were 10-20-fold higher than with the MF59-like AddaVax adjuvant. In both models, a single immunisation with CMS adjuvant revealed similar or higher titres than two immunisations with either benchmark, without detectable systemic and local adverse effects. Despite striking chemical similarities with monophospholipid A (MPL), CMS adjuvant did not activate human TLR4 expressed on HEK cells. We concluded that the synthetic CMS adjuvant is a promising candidate for poor immunogens and single-shot vaccines and that rise in body temperature, local reactions or activation of TLR4 is not a pre-requisite for high adjuvanticity. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Marketing orientation in pharmaceutical industry

Directory of Open Access Journals (Sweden)

Prošić Danica

2006-01-01

Full Text Available Pharmaceutical companies are major stakeholders in the global health agenda Virtually all drugs used by patients in Europe reach markets through the promotion tactics of a small number of corporations with a tremendous impact on global health. The sector is both fast growing and highly profitable. Effective marketing strategies are a crucial ingredient in making sure pharmaceutical products and profits flow in a virtuous cycle. At first glance, the relationship between doctors and drug companies, as well as advertising practices for over-the-counter medication, appears tightly regulated. According to many consumer organizations, drug promotion in Europe today can be characterized as nice and friendly marketing. This refers to the creation of a false sense of trust that consumers associate with branded pharmaceutical products, as a result of pharmaceutical marketing efforts disguised as genuine corporate responsibility.

PARTICULARITIES OF MODERN PHARMACEUTICAL PROMOTION

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Юрий Владимирович Тарасов

2014-02-01

Full Text Available Pharmaceutical products market is one of the most saturated consumers’ markets. Characteristic features of it are: high competition, fierce struggle for the customer, specific technologies of promotion. In conditions of globalization and increase in competition both in world pharmaceutical market and in the market of medicines and goods of medical purpose in Russia modern marketing techniques of promotion of the products to the end consumers are the key tools for strengthening market positions – both of producers of pharmaceutical goods and their suppliers, distributors, big whole-sale companies. Among main tools of promotion are: advertising, public relations, stimulation of sales on the market of medicines, personal sales, computer technologies. The article describes different technologies of promotion of medicines: indoor-advertising, hot lines, pharmaceutical exhibitions, packing. DOI: http://dx.doi.org/10.12731/2218-7405-2013-12-1

Adjuvant therapy for locally advanced renal cell cancer: A systematic review with meta-analysis

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Lima Carmen SP

2011-03-01

Full Text Available Abstract Background Many adjuvant trials have been undertaken in an attempt to reduce the risk of recurrence among patients who undergo surgical resection for locally advanced renal cancer. However, no clear benefit has been identified to date. This systematic review was conducted to examine the exact role of adjuvant therapy in renal cancer setting. Methods Randomized controlled trials were searched comparing adjuvant therapy (chemotherapy, vaccine, immunotherapy, biochemotherapy versus no active treatment after surgery among renal cell cancer patients. Outcomes were overall survival (OS, disease-free survival (DFS, and severe toxicities. Risk ratios (RR, hazard ratios (HR and 95% confidence intervals were calculated using a fixed-effects meta-analysis. Heterogeneity was measured by I2. Different strategies of adjuvant treatment were evaluated separately. Results Ten studies (2,609 patients were included. Adjuvant therapy provided no benefits in terms of OS (HR 1.07; 95%CI 0.89 to 1.28; P = 0.48 I2 = 0% or DFS (HR 1.03; 95%CI 0.87 to 1.21; P = 0.77 I2 = 15% when compared to no treatment. No subgroup analysis (immunotherapy, vaccines, biochemotherapy and hormone therapy had relevant results. Toxicity evaluation depicted a significantly higher frequency of serious adverse events in the adjuvant group. Conclusions This analysis provided no support for the hypothesis that the agents studied provide any clinical benefit for renal cancer patients although they increase the risk of toxic effects. Randomized trials are underway to test targeted therapies, which might open a new therapeutic frontier. Until these trials yield results, no adjuvant therapy can be recommended for patients who undergo surgical resection for renal cell cancer.

National transparency assessment of Kuwait's pharmaceutical sector.

Science.gov (United States)

Badawi, Dalia A; Alkhamis, Yousif; Qaddoumi, Mohammad; Behbehani, Kazem

2015-09-01

Corruption is one of several factors that may hinder the access to pharmaceuticals. Since Kuwait has the highest per-capita spending on pharmaceuticals in the region, we wanted to evaluate the level of transparency in its pharmaceutical sector using an established assessment tool adapted by the World Health Organization. Standardized questionnaires were conducted via semi-structured interviews with key informants to measure the level of transparency in eight functions of the public pharmaceutical sector. The scores for the degree of vulnerability to corruption reflected marginal to moderate venerability to corruption for most pharmaceutical sectors. The perceived strengths included availability of appropriate laws, the presence of clear standard operating procedures, and the use of an efficient registration/distribution system. Weaknesses included lack of conflict of interest guidelines and written terms of reference, absence of pharmacoeconomic studies, and inconsistencies in law enforcement. Findings reveal that few functions of Kuwait pharmaceutical sector remain fairly vulnerable to corruption. However, the willingness of Kuwait Ministry of Health to adopt the assessment study and the acknowledgement of the weaknesses of current processes of the pharmaceutical sector may assist to achieve a transparent pharmaceutical system in the near future. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Strategic Management of Innovations at Pharmaceutical Enterprises

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Honcharova Svіtlana Yu.

2014-01-01

Full Text Available The article is devoted to theoretical and practical issues of the use of the concept of strategic management of innovations at pharmaceutical enterprises. It studies main barriers, which restrict development of Ukrainian pharmaceutical enterprises. It analyses the state and tendencies of development of innovation activity of pharmaceutical enterprises and studies foreign experience of innovation activity. It marks out specific features of strategic management of innovation development in pharmaceutical industry. It specifies the role and advantages of methods of strategic analysis in the system of management of a pharmaceutical enterprise. It considers the essence of “innovation development” and “innovation model of development” notions and analyses their organisational and legal provision. It justifies strategic tasks of the pharmaceutical filed to focus on in order to achieve a breakthrough when building an innovation model of economic development. The article proves that the most important factors that ensure growth of efficiency of pharmaceutical production are: wide application of the concept of strategic management and creation of innovations.

[Chinese medicine industry 4.0：advancing digital pharmaceutical manufacture toward intelligent pharmaceutical manufacture].

Science.gov (United States)

Cheng, Yi-Yu; Qu, Hai-Bin; Zhang, Bo-Li

2016-01-01

A perspective analysis on the technological innovation in pharmaceutical engineering of Chinese medicine unveils a vision on "Future Factory" of Chinese medicine industry in mind. The strategy as well as the technical roadmap of "Chinese medicine industry 4.0" is proposed, with the projection of related core technology system. It is clarified that the technical development path of Chinese medicine industry from digital manufacture to intelligent manufacture. On the basis of precisely defining technical terms such as process control, on-line detection and process quality monitoring for Chinese medicine manufacture, the technical concepts and characteristics of intelligent pharmaceutical manufacture as well as digital pharmaceutical manufacture are elaborated. Promoting wide applications of digital manufacturing technology of Chinese medicine is strongly recommended. Through completely informationized manufacturing processes and multi-discipline cluster innovation, intelligent manufacturing technology of Chinese medicine should be developed, which would provide a new driving force for Chinese medicine industry in technology upgrade, product quality enhancement and efficiency improvement. Copyright© by the Chinese Pharmaceutical Association.

Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial.

Science.gov (United States)

Piccart-Gebhart, Martine; Holmes, Eileen; Baselga, José; de Azambuja, Evandro; Dueck, Amylou C; Viale, Giuseppe; Zujewski, Jo Anne; Goldhirsch, Aron; Armour, Alison; Pritchard, Kathleen I; McCullough, Ann E; Dolci, Stella; McFadden, Eleanor; Holmes, Andrew P; Tonghua, Liu; Eidtmann, Holger; Dinh, Phuong; Di Cosimo, Serena; Harbeck, Nadia; Tjulandin, Sergei; Im, Young-Hyuck; Huang, Chiun-Sheng; Diéras, Véronique; Hillman, David W; Wolff, Antonio C; Jackisch, Christian; Lang, Istvan; Untch, Michael; Smith, Ian; Boyle, Frances; Xu, Binghe; Gomez, Henry; Suter, Thomas; Gelber, Richard D; Perez, Edith A

2016-04-01

Lapatinib (L) plus trastuzumab (T) improves outcomes for metastatic human epidermal growth factor 2-positive breast cancer and increases the pathologic complete response in the neoadjuvant setting, but their role as adjuvant therapy remains uncertain. In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial, patients with centrally confirmed human epidermal growth factor 2-positive early breast cancer were randomly assigned to 1 year of adjuvant therapy with T, L, their sequence (T→L), or their combination (L+T). The primary end point was disease-free survival (DFS), with 850 events required for 80% power to detect a hazard ratio (HR) of 0.8 for L+T versus T. Between June 2007 and July 2011, 8,381 patients were enrolled. In 2011, due to futility to demonstrate noninferiority of L versus T, the L arm was closed, and patients free of disease were offered adjuvant T. A protocol modification required P ≤ .025 for the two remaining pairwise comparisons. At a protocol-specified analysis with a median follow-up of 4.5 years, a 16% reduction in the DFS hazard rate was observed with L+T compared with T (555 DFS events; HR, 0.84; 97.5% CI, 0.70 to 1.02; P = .048), and a 4% reduction was observed with T→L compared with T (HR, 0.96; 97.5% CI, 0.80 to 1.15; P = .61). L-treated patients experienced more diarrhea, cutaneous rash, and hepatic toxicity compared with T-treated patients. The incidence of cardiac toxicity was low in all treatment arms. Adjuvant treatment that includes L did not significantly improve DFS compared with T alone and added toxicity. One year of adjuvant T remains standard of care. © 2015 by American Society of Clinical Oncology.

Rheology in Pharmaceutical Sciences

DEFF Research Database (Denmark)

Aho, Johanna; Hvidt, Søren; Baldursdottir, Stefania

2016-01-01

Rheology is the science of flow and deformation of matter. Particularly gels and non-Newtonian fluids, which exhibit complex flow behavior, are frequently encountered in pharmaceutical engineering and manufacturing, or when dealing with various in vivo fluids. Therefore understanding rheology......, together with the common measurement techniques and their practical applications. Examples of the use of rheological techniques in the pharmaceutical field, as well as other closely related fields such as food and polymer science, are also given....... is important, and the ability to use rheological characterization tools is of great importance for any pharmaceutical scientist involved in the field. Flow can be generated by shear or extensional deformations, or a combination of both. This chapter introduces the basics of both shear and extensional rheology...

Pharmaceutical Public-Private Partnerships

DEFF Research Database (Denmark)

Bagley, Constance; Tvarnø, Christina D.

2014-01-01

This article provides a game theory and law-and-management analysis of for- profit pharmaceutical public-private partnerships, a complex type of legal arrangement in the highly regulated pharmaceutical industry. A pharmaceutical public-private partnership (PPPP) agreement is a legally binding...... and a practical perspective on how properly crafted PPPP arrangements can promote innovation more efficiently than traditional self-optimizing contracts. In particular, a properly framed binding contract, coupled with respect for positive incentives, can move the parties away from an inefficient prisoners...... systems to build and share innovation. When coupled with appropriate attention to the difficult task of coordinating the actions of interdependent actors, a PPPP arrangement can enhance the likelihood of successful commercialization of pharmacological discoveries by flipping the par- ties’ incentives...

Adjuvant Chemotherapy Improves the Probability of Freedom From Recurrence in Patients With Resected Stage IB Lung Adenocarcinoma.

Science.gov (United States)

Hung, Jung-Jyh; Wu, Yu-Chung; Chou, Teh-Ying; Jeng, Wen-Juei; Yeh, Yi-Chen; Hsu, Wen-Hu

2016-04-01

The benefit of adjuvant chemotherapy remains controversial for patients with stage IB non-small-cell lung cancer (NSCLC). This study investigated the effect of adjuvant chemotherapy and the predictors of benefit from adjuvant chemotherapy in patients with stage IB lung adenocarcinoma. A total of 243 patients with completely resected pathologic stage IB lung adenocarcinoma were included in the study. Predictors of the benefits of improved overall survival (OS) or probability of freedom from recurrence (FFR) from platinum-based adjuvant chemotherapy in patients with resected stage IB lung adenocarcinoma were investigated. Among the 243 patients, 70 (28.8%) had received platinum-based doublet adjuvant chemotherapy. A micropapillary/solid-predominant pattern (versus an acinar/papillary-predominant pattern) was a significantly worse prognostic factor for probability of FFR (p = 0.033). Although adjuvant chemotherapy (versus surgical intervention alone) was not a significant prognostic factor for OS (p = 0.303), it was a significant prognostic factor for a better probability of FFR (p = 0.029) on multivariate analysis. In propensity-score-matched pairs, there was no significant difference in OS between patients who received adjuvant chemotherapy and those who did not (p = 0.386). Patients who received adjuvant chemotherapy had a significantly better probability of FFR than those who did not (p = 0.043). For patients with a predominantly micropapillary/solid pattern, adjuvant chemotherapy (p = 0.033) was a significant prognostic factor for a better probability of FFR on multivariate analysis. Adjuvant chemotherapy is a favorable prognostic factor for the probability of FFR in patients with stage IB lung adenocarcinoma, particularly in those with a micropapillary/solid-predominant pattern. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

[Caprine arthritis-encephalitis: trial of an adjuvant vaccine preparation. I. Clinical and virological study].

Science.gov (United States)

Russo, P; Vitu, C; Fontaine, J J; Vignoni, M

1993-04-01

In purpose to protect goats against caprine arthritis encephalitis virus (CAEV), the first group of kids (I) was inoculated with purified, inactivated and adjuvant-treated virions, the second group (II) with adjuvant and the third one (III) with culture medium. 2-4 months later, the three groups were challenged with virulent CAEV by intraarticular route. On the clinical level, vaccinated and challenged kids show more early and severe arthritis than other groups. On the virological level, isolation of lentivirus from white blood cells and different organs is more important in group I than groups II and III. Therefore, vaccinations with inactivated and adjuvant-treated virions do not protect against a virulent challenge; there is an enhancement of lesions. We note that the adjuvant elicits a mild non-specific protection against virulent challenge.

Further studies on the H-2 linked dependence of the adjuvant action of Brucella abortus

International Nuclear Information System (INIS)

Oth, D.; Sabolovic, D.

1978-01-01

The B 19S strain of Brucella abortus has been found to act as an adjuvant to the anti-sheep red blood cell (SRBC) reaction in some congenic strains of mice but not in others. If the recipient was H-2sup(b), there was no adjuvant effect (B 19S); neither was there (thymus-dependent) anti-B 19S reaction as measured by thymocyte activation and change of electrophoretic mobility. In contrast, there was a thymus-independent anti-B 19S reaction (production of haemagglutinins) as good in the H-2sup(b) mice as in the others. Experiments with T cell deprived mice showed that the adjuvant action of B 19S was thymus-dependent. As the anti-SRBC reaction without adjuvant was also thymus-dependent, it was difficult to distinguish anti-SRBC and anti-B reactions from the adjuvant action of B 19S on the anti-SRBC reaction. Several explanations are possible, all involving H-2 (Isup(r)) controlled thymus dependent mechanisms. (author)

CpG-DNA enhancement the immune elicited as adjuvant of foot- and- mouth disease vaccine

Directory of Open Access Journals (Sweden)

Morshedi, A.

2010-01-01

Full Text Available In the present study the effect of the locally produced genetic adjuvant of ginea pig specific CpG-motif-containing oligodeoxynucleotide (CpG-ODN in an inactivated FMD virus vaccine was evaluated. Boosting the ginea pigs with FMD vaccine along with CpG-ODN adjuvant produced relatively higher ratio (5-fold of FMDV-specific IgG2a / IgG1 than those vaccinated in the absence of CpG-ODN. The neutralizing antibody (NA titer induced by FMD vaccine along with CpG-ODN adjuvant was significantly higher (8-fold than NA titer induced by the classical FMD vaccine in Alum adjuvant. The titer of NA and virus clearance from serum was consistently and significantly higher in animals primed with FMD vaccine and boosted by CpG-ODN than the classical FMD vaccine. The results of this study showed the potential of CpG-ODN as a genetic adjuvant to FMD vaccine in the development of Th1 responses.

Adjuvant Therapy: Treatment to Keep Cancer from Returning

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... significant side effects, and these treatments don't benefit everyone. Types of cancer treatment that are used as adjuvant therapy include: Chemotherapy. Chemotherapy uses drugs to kill cancer cells throughout ...

Adjuvant chemotherapy for endometrial cancer after hysterectomy

Science.gov (United States)

Johnson, Nick; Bryant, Andrew; Miles, Tracie; Hogberg, Thomas; Cornes, Paul

2014-01-01

Background Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. Objectives To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. Data collection and analysis We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. Main results Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly

Conceptualizing Pharmaceutical Plants

DEFF Research Database (Denmark)

Larsen, Bent Dalgaard; Jensen, Klaes Ladeby; Gjøl, Mikkel

2006-01-01

In the conceptual design phase of pharmaceutical plants as much as 80%-90% of the total cost of a project is committed. It is therefore essential that the chosen concept is viable. In this design process configuration and 3D models can help validate the decisions made. Designing 3D models...... is a complex task and requires skilled users. We demonstrate that a simple 2D/3D configuration tool can support conceptualizing of pharmaceutical plants. Present paper reports on preliminary results from a full scale implementation project at a Danish engineering company....

PSE in Pharmaceutical Process Development

DEFF Research Database (Denmark)

Gernaey, Krist; Cervera Padrell, Albert Emili; Woodley, John

2011-01-01

The pharmaceutical industry is under growing pressure to increase efficiency, both in production and in process development. This paper will discuss the use of Process Systems Engineering (PSE) methods in pharmaceutical process development, and searches for answers to questions such as: Which PSE...

Adjuvant radiotherapy after radical prostatectomy: A failure of marketing-based medicine?

International Nuclear Information System (INIS)

Shakespeare, Thomas P.

2016-01-01

Adjuvant radiotherapy for high-risk patients after radical prostatectomy has been shown to reduce local and metastatic failure, improve overall survival and improve quality of life (QOL). The evidence, based on three randomised studies and a meta-analysis, is so compelling that the national and internatioanl professional bodies, representing urologists and radiation oncologist alike, recommend that high-risk patients be offered immediate adjuvant radiotherapy. Despite this being the standard of care, few patients fo on to recive it. This paper looks at the possibilities of why this is so, highlighting that it could possibly be related to poor marketing, communication and delivery of health information to patients and professional alike. It concludes that we need a more coordinated way to increase utilisation of the gold standard adjuvant radiotherapy post-radical prostatectomy, perhaps learning some valuable lessons from the business community.

Parenteral adjuvant potential of recombinant B subunit of Escherichia coli heat-labile enterotoxin

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Carlos Eduardo Pouey da Cunha

Full Text Available BACKGROUND The B subunit of Escherichia coli heat-labile enterotoxin (LTB is a potent mucosal immune adjuvant. However, there is little information about LTB's potential as a parenteral adjuvant. OBJECTIVES We aimed at evaluating and better understanding rLTB's potential as a parenteral adjuvant using the fused R1 repeat of Mycoplasma hyopneumoniae P97 adhesin as an antigen to characterise the humoral immune response induced by this construct and comparing it to that generated when aluminium hydroxide is used as adjuvant instead. METHODS BALB/c mice were immunised intraperitoneally with either rLTBR1 or recombinant R1 adsorbed onto aluminium hydroxide. The levels of systemic anti-rR1 antibodies (total Ig, IgG1, IgG2a, and IgA were assessed by enzyme-linked immunosorbent assay (ELISA. The ratio of IgG1 and IgG2a was used to characterise a Th1, Th2, or mixed Th1/Th2 immune response. FINDINGS Western blot confirmed rR1, either alone or fused to LTB, remained antigenic; anti-cholera toxin ELISA confirmed that LTB retained its activity when expressed in a heterologous system. Mice immunised with the rLTBR1 fusion protein produced approximately twice as much anti-rR1 immunoglobulins as mice vaccinated with rR1 adsorbed onto aluminium hydroxide. Animals vaccinated with either rLTBR1 or rR1 adsorbed onto aluminium hydroxide presented a mixed Th1/Th2 immune response. We speculate this might be a result of rR1 immune modulation rather than adjuvant modulation. Mice immunised with rLTBR1 produced approximately 1.5-fold more serum IgA than animals immunised with rR1 and aluminium hydroxide. MAIN CONCLUSIONS The results suggest that rLTB is a more powerful parenteral adjuvant than aluminium hydroxide when administered intraperitoneally as it induced higher antibody titres. Therefore, we recommend that rLTB be considered an alternative adjuvant, even if different administration routes are employed.

Adjuvant irradiation improves the outcome of patients with rectal cancer following local excision

International Nuclear Information System (INIS)

Chakravarti, Arnab; Willett, Christopher G.; Shellito, Paul; Kaufman, Donald; Daley, William J.

1997-01-01

PURPOSE: the long-term outcomes of patients undergoing local excision with or without pelvic irradiation were examined to define the role of adjuvant irradiation following local excision of T1 and T2 rectal cancers. METHODS: From January 1966 to January 1997, 114 patients underwent local excision for rectal cancer. Fifty-nine patients underwent local excision alone, and 55 patients received adjuvant pelvic irradiation (45 Gy to 65.8 Gy)+/-concurrent 5-fluorouracil chemotherapy. Outcome was assessed by treatment, stage, and pathologic features of tumor grade and lymphatic/venous vessel involvement. RESULTS: Of the 114 patients treated by local excision, 90 had T1/T2 tumors. The 5-year actuarial local control (LC) and recurrence-free survival (RFS) of these 90 patients are shown (with numbers of patients at risk at 5 years) in the table below. The 5-year actuarial local control and recurrence-free survival (RFS) for T1/T2 patients treated by local excision alone was 85% and 77%, respectively. The corresponding values for patients undergoing local excision and adjuvant irradiation alone were 88% and 78%, respectively. All 20 patients treated by adjuvant chemoradiation achieved 5-year actuarial local control and had a recurrence-free survival of 88%. The improved outcomes in the adjuvant radiation group become more impressive when the higher T stage distribution of this group is considered. Fifty-five percent of the group receiving adjuvant radiation were stage T2 compared to only 14% of patients treated by local excision alone. Subgroup analysis was performed on those features recognized as poor prognostic factors including poorly differentiated histology and lymphatic vascular invasion. Patients in the local excision alone group with one or more adverse pathologic features had reduced rates of local control compared to those with the absence of such features (38% vs. 91%, respectively, p=0.02). In comparison, the 5 patients with poor prognostic features treated by

Effect of adjuvants on responses to skin immunization by microneedles coated with influenza subunit vaccine.

Directory of Open Access Journals (Sweden)

William C Weldon

Full Text Available Recent studies have demonstrated the effectiveness of vaccine delivery to the skin by vaccine-coated microneedles; however there is little information on the effects of adjuvants using this approach for vaccination. Here we investigate the use of TLR ligands as adjuvants with skin-based delivery of influenza subunit vaccine. BALB/c mice received 1 µg of monovalent H1N1 subunit vaccine alone or with 1 µg of imiquimod or poly(I:C individually or in combination via coated microneedle patches inserted into the skin. Poly(I:C adjuvanted subunit influenza vaccine induced similar antigen-specific immune responses compared to vaccine alone when delivered to the skin by microneedles. However, imiquimod-adjuvanted vaccine elicited higher levels of serum IgG2a antibodies and increased hemagglutination inhibition titers compared to vaccine alone, suggesting enhanced induction of functional antibodies. In addition, imiquimod-adjuvanted vaccine induced a robust IFN-γ cellular response. These responses correlated with improved protection compared to influenza subunit vaccine alone, as well as reduced viral replication and production of pro-inflammatory cytokines in the lungs. The finding that microneedle delivery of imiquimod with influenza subunit vaccine induces improved immune responses compared to vaccine alone supports the use of TLR7 ligands as adjuvants for skin-based influenza vaccines.

The role of adjuvant radiotherapy in the treatment of resectable desmoid tumors

International Nuclear Information System (INIS)

Goy, Barry W.; Lee, Steve P.; Eilber, Frederick; Dorey, Fred; Eckardt, Jeffrey; Fu, Yao-Shi; Juillard, Guy J. F.; Selch, Michael T.

1997-01-01

Purpose: Desmoid tumors have a high propensity for local recurrence with surgical resection. There are many reports describing good responses of desmoid tumors to irradiation, but none have clearly established the indications for adjuvant radiotherapy in treating resectable desmoid tumors. Methods and Materials: A retrospective analysis was performed on 61 patients with resectable desmoid tumor(s) who were treated at our institution from 1965 to February of 1992. Five patients had multifocal disease and are analyzed separately. Fifty-six patients had unifocal disease, of which 34 had positive surgical margins. Forty-five of the 56 patients with unifocal disease were treated with surgery alone, while 11 were treated with surgery plus adjuvant radiotherapy. Median follow-up was 6 years. Local control was measured from the last day of treatment, and all cases were reviewed by our Department of Pathology. Results: Multivariate analysis of the 56 patients with unifocal disease revealed that positive margins independently predicted for local recurrence (p ≤ 0.01). Only 3 of 22 patients with clear margins experienced a local recurrence, with a 6-year actuarial local control of 85%. Multivariate analysis of the 34 patients with positive margins revealed that adjuvant radiotherapy independently predicted for improved local control (p 0.01), and patients with recurrent disease had a slightly higher risk of local recurrence (p = 0.08). The 6-year actuarial local control determined by Kaplan-Meier for patients with unifocal disease and positive margins was 32% (±12%) with surgery alone, and 78% (±14%) with surgery plus adjuvant radiotherapy (p = 0.02). Subgroup analysis of the patients with positive margins and recurrent disease revealed that those treated with surgery alone had a 6-year actuarial local control of 0% vs. 80% for those treated with surgery plus radiotherapy (p ≤ 0.01). Patients with positive margins and primary disease had a trend towards improved local

Analysis of adjuvant treatment with chemoradiation in gastric cancer

International Nuclear Information System (INIS)

Fallas Solis, Elias

2008-01-01

The Hospital San Juan de Dios has analyzed the benefit of patients with gastric cancer who undergo surgery after receiving adjuvant chemoradiation. A retrospective study was performed reviewing records of patients during the period 1 January 2001 to December 31, 2005. These patients have been discharged with a diagnosis of gastric cancer and have received a complete resection with curative gastric malignancy and adjuvant chemoradiation according to the protocol established by Dr. MacDonald. In the study 0116. 743 patients were discharged to Hospital San Juan de Dios, 1 in 20 has been possible to diagnose gastric cancer at early stages for a total of 28 patients. The results obtained were compared at the Hospital San Juan de Dios with those published by Dr. MacDonald. The over-life of 3 years in the chemoradiation group in Hospital San Juan de Dios has been of 42.9% and 50% in the study MacDonald. The group that has not received adjuvant the over-life in the same period has been of 20 % in HSJD and 41% in the study MacDonald, being lower percentage of patients with this over-life, but greater range of difference. [es

Contribution of hospital effluents to the load of pharmaceuticals in urban wastewaters: identification of ecologically relevant pharmaceuticals.

Science.gov (United States)

Santos, Lúcia H M L M; Gros, Meritxell; Rodriguez-Mozaz, Sara; Delerue-Matos, Cristina; Pena, Angelina; Barceló, Damià; Montenegro, M Conceição B S M

2013-09-01

The impact of effluent wastewaters from four different hospitals: a university (1456 beds), a general (350 beds), a pediatric (110 beds) and a maternity hospital (96 beds), which are conveyed to the same wastewater treatment plant (WWTP), was evaluated in the receiving urban wastewaters. The occurrence of 78 pharmaceuticals belonging to several therapeutic classes was assessed in hospital effluents and WWTP wastewaters (influent and effluent) as well as the contribution of each hospital in WWTP influent in terms of pharmaceutical load. Results indicate that pharmaceuticals are widespread pollutants in both hospital and urban wastewaters. The contribution of hospitals to the input of pharmaceuticals in urban wastewaters widely varies, according to their dimension. The estimated total mass loadings were 306 g d(-1) for the university hospital, 155 g d(-1) for the general one, 14 g d(-1) for the pediatric hospital and 1.5 g d(-1) for the maternity hospital, showing that the biggest hospitals have a greater contribution to the total mass load of pharmaceuticals. Furthermore, analysis of individual contributions of each therapeutic group showed that NSAIDs, analgesics and antibiotics are among the groups with the highest inputs. Removal efficiency can go from over 90% for pharmaceuticals like acetaminophen and ibuprofen to not removal for β-blockers and salbutamol. Total mass load of pharmaceuticals into receiving surface waters was estimated between 5 and 14 g/d/1000 inhabitants. Finally, the environmental risk posed by pharmaceuticals detected in hospital and WWTP effluents was assessed by means of hazard quotients toward different trophic levels (algae, daphnids and fish). Several pharmaceuticals present in the different matrices were identified as potentially hazardous to aquatic organisms, showing that especial attention should be paid to antibiotics such as ciprofloxacin, ofloxacin, sulfamethoxazole, azithromycin and clarithromycin, since their hazard quotients

Novel methodology for pharmaceutical expenditure forecast

OpenAIRE

Vataire, Anne-Lise; Cetinsoy, Laurent; Aball?a, Samuel; R?muzat, C?cile; Urbinati, Duccio; Kornfeld, ?sa; Mzoughi, Olfa; Toumi, Mondher

2014-01-01

Background and objective: The value appreciation of new drugs across countries today features a disruption that is making the historical data that are used for forecasting pharmaceutical expenditure poorly reliable. Forecasting methods rarely addressed uncertainty. The objective of this project was to propose a methodology to perform pharmaceutical expenditure forecasting that integrates expected policy changes and uncertainty (developed for the European Commission as the ‘EU Pharmaceutical e...

Bioremediation Kinetics of Pharmaceutical Industrial Effluent

OpenAIRE

M. Šabić; M. Vuković Domanovac; Z. Findrik Blažević; E. Meštrović

2015-01-01

In recent years, concerns about the occurrence and fate of pharmaceuticals that could be present in water and wastewater has gained increasing attention. With the public’s enhanced awareness of eco-safety, environmentally benign methods based on microorganisms have become more accepted methods of removing pollutants from aquatic systems. This study investigates bioremediation of pharmaceutical wastewater from pharmaceutical company Pliva Hrvatska d.o.o., using activated sludge and bioaugmente...

[Freeze drying process optimization of ginger juice-adjuvant for Chinese materia medica processing and stability of freeze-dried ginger juice powder].

Science.gov (United States)

Yang, Chun-Yu; Guo, Feng-Qian; Zang, Chen; Cao, Hui; Zhang, Bao-Xian

2018-02-01

Ginger juice， a commonly used adjuvant for Chinese materia medica， is applied in processing of multiple Chinese herbal decoction pieces. Because of the raw materials and preparation process of ginger juice， it is difficult to be preserved for a long time， and the dosage of ginger juice in the processing can not be determined base on its content of main compositions. Ginger juice from different sources is hard to achieve consistent effect during the processing of traditional Chinese herbal decoction pieces. Based on the previous studies， the freeze drying of ginger juice under different shelf temperatures and vacuum degrees were studied， and the optimized freeze drying condition of ginger juice was determined. The content determination method for 6-gingerol， 8-gingerol， 10-gingerol and 6-shagaol in ginger juice and redissolved ginger juice was established. The content changes of 6-gingerol， 8-gingerol， 10-gingerol， 6-gingerol， 6-shagaol， volatile oil and total phenol were studied through the drying process and 30 days preservation period. The results showed that the freeze drying time of ginger juice was shortened after process optimization; the compositions basically remained unchanged after freeze drying， and there was no significant changes in the total phenol content and gingerol content， but the volatile oil content was significantly decreased( P <0.05). Within 30 days， the contents of gingerol， total phenol， and volatile oil were on the decline as a whole. This study has preliminarily proved the feasibility of freeze-drying process of ginger juice as an adjuvant for Chinese medicine processing. Copyright© by the Chinese Pharmaceutical Association.

The effect of adjuvant radiation on survival in early stage clear cell ovarian carcinoma.

Science.gov (United States)

Hogen, Liat; Thomas, Gillian; Bernardini, Marcus; Bassiouny, Dina; Brar, Harinder; Gien, Lilian T; Rosen, Barry; Le, Lisa; Vicus, Danielle

2016-11-01

To assess the impact of adjuvant radiotherapy (RT) on survival in patients with stage I and II ovarian clear cell carcinoma (OCCC). Data collection and analysis of stage I and II OCCC patients treated at two tertiary centers in Toronto, between 1995 and 2014, was performed. Descriptive statistics and Kaplan-Meier survival probability estimates were completed. The log-rank test was used to compare survival curves. 163 patients were eligible. 44 (27%) patients were treated with adjuvant RT: 37 of them received adjuvant chemotherapy (CT), and 7 had RT only. In the no-RT group, there were 119 patients: 83 patients received adjuvant CT and 36 had no adjuvant treatment. The 10year progression free survival (PFS) was 65% for patients treated with RT, and 59% no-RT patients. There were a total of 41 (25%) recurrences in the cohort: 12 (27.2%) patients in RT group and 29 (24.3%) in the no-RT group. On multivariable analysis, adjuvant RT was not significantly associated with an increased PFS (0.85 (0.44-1.63) p=0.63) or overall survival (OS) (0.84 (0.39-1.82) p=0.66). In the subset of 59 patients defined as high-risk: stage IC with positive cytology and/or surface involvement and stage II: RT was not found to be associated with a better PFS (HR 1.18 (95% CI: 0.55-2.54) or O S(HR 1.04 (95% CI: 0.40-2.69)). Adjuvant RT was not found to be associated with a survival benefit in patients with stage I and II ovarian clear cell carcinoma or in a high risk subset of patients including stage IC cytology positive/surface involvement and stage II patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Vulnerabilities to misinformation in online pharmaceutical marketing.

Science.gov (United States)

De Freitas, Julian; Falls, Brian A; Haque, Omar S; Bursztajn, Harold J

2013-05-01

Given the large percentage of Internet users who search for health information online, pharmaceutical companies have invested significantly in online marketing of their products. Although online pharmaceutical marketing can potentially benefit both physicians and patients, it can also harm these groups by misleading them. Indeed, some pharmaceutical companies have been guilty of undue influence, which has threatened public health and trust. We conducted a review of the available literature on online pharmaceutical marketing, undue influence and the psychology of decision-making, in order to identify factors that contribute to Internet users' vulnerability to online pharmaceutical misinformation. We find five converging factors: Internet dependence, excessive trust in the veracity of online information, unawareness of pharmaceutical company influence, social isolation and detail fixation. As the Internet continues to change, it is important that regulators keep in mind not only misinformation that surrounds new web technologies and their contents, but also the factors that make Internet users vulnerable to misinformation in the first place. Psychological components are a critical, although often neglected, risk factor for Internet users becoming misinformed upon exposure to online pharmaceutical marketing. Awareness of these psychological factors may help Internet users attentively and safely navigate an evolving web terrain.

ERCC1 as a biomarker for bladder cancer patients likely to benefit from adjuvant chemotherapy

International Nuclear Information System (INIS)

Sun, Jong-Mu; Choi, Han Yong; Lim, Ho Yeong; Sung, Ji-Youn; Park, Se Hoon; Kwon, Ghee Young; Jeong, Byong Chang; Seo, Seong Il; Jeon, Seong Soo; Lee, Hyun Moo; Jo, Jisuk

2012-01-01

The role of adjuvant chemotherapy and the value of molecular biomarkers in bladder cancer have not been determined. We aimed to assess the predictive and prognostic values of excision repair cross-complementation 1 (ERCC1) in identifying appropriate patients who may potentially benefit from adjuvant chemotherapy for bladder cancer. A retrospective analysis was performed on 93 patients with completely resected transitional cell carcinoma of the bladder. ERCC1 expression was assessed by immunohistochemistry. ERCC1 expression was analyzed in 57 patients treated with adjuvant gemcitabine plus cisplatin chemotherapy and 36 who were not treated. Among 93 patients, ERCC1 expression was positive in 54 (58.1%) and negative in 39 (41.9%). ERCC1 positivity was significantly associated with longer survival (adjusted hazard ratio for death, 0.12, 95% confidence interval [CI] 0.014-0.99; P = 0.049) in the group without adjuvant chemotherapy while ERCC1 positivity was associated with shorter survival among patients who have received adjuvant chemotherapy (adjusted hazard ratio for death, 2.64; 95% CI 1.01-6.85; P = 0.047). Therefore, clinical benefit from adjuvant chemotherapy was associated with ERCC1 negativity as measured by overall survival (test for interaction, P = 0.034) and by disease-free survival (test for interaction, P = 0.20). Among patients with completely resected transitional cell carcinoma of the bladder, those with ERCC1-negative tumors seemed to benefit more from adjuvant gemcitabine plus cisplatin chemotherapy than those with ERCC1-positive tumors. Future prospective, randomized studies are warranted to confirm our findings

Adjuvant-Mediated Epitope Specificity and Enhanced Neutralizing Activity of Antibodies Targeting Dengue Virus Envelope Protein

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Denicar Lina Nascimento Fabris Maeda

2017-09-01

Full Text Available The heat-labile toxins (LT produced by enterotoxigenic Escherichia coli display adjuvant effects to coadministered antigens, leading to enhanced production of serum antibodies. Despite extensive knowledge of the adjuvant properties of LT derivatives, including in vitro-generated non-toxic mutant forms, little is known about the capacity of these adjuvants to modulate the epitope specificity of antibodies directed against antigens. This study characterizes the role of LT and its non-toxic B subunit (LTB in the modulation of antibody responses to a coadministered antigen, the dengue virus (DENV envelope glycoprotein domain III (EDIII, which binds to surface receptors and mediates virus entry into host cells. In contrast to non-adjuvanted or alum-adjuvanted formulations, antibodies induced in mice immunized with LT or LTB showed enhanced virus-neutralization effects that were not ascribed to a subclass shift or antigen affinity. Nonetheless, immunosignature analyses revealed that purified LT-adjuvanted EDIII-specific antibodies display distinct epitope-binding patterns with regard to antibodies raised in mice immunized with EDIII or the alum-adjuvanted vaccine. Notably, the analyses led to the identification of a specific EDIII epitope located in the EF to FG loop, which is involved in the entry of DENV into eukaryotic cells. The present results demonstrate that LT and LTB modulate the epitope specificity of antibodies generated after immunization with coadministered antigens that, in the case of EDIII, was associated with the induction of neutralizing antibody responses. These results open perspectives for the more rational development of vaccines with enhanced protective effects against DENV infections.

Outcomes of curettage and anhydrous alcohol adjuvant for low-grade chondrosarcoma of long bone.

Science.gov (United States)

Kim, Wanlim; Han, Ilkyu; Kim, Eo Jin; Kang, Seungcheol; Kim, Han-Soo

2015-06-01

Low-grade chondrosarcoma of long bones can be treated successfully with extended intralesional curettage using adjuvants. However, there is no study reporting the use of anhydrous alcohol as an adjuvant in the treatment of low-grade chondrosarcoma. We asked (1) whether intralesional curettage and anhydrous alcohol adjuvant for low-grade chondrosarcoma is associated with good oncologic outcomes; and we report (2) the complications of the procedure. Thirty-six patients (13 men, 23 women) with a mean age of 46 years (range, 18-67 years) were treated for low-grade chondrosarcoma and followed up for a median of 62 months (range, 24-169 months). After intralesional curettage, and additional burring, anhydrous alcohol was used as an adjuvant therapy. At the time of last follow-up, there were no local recurrences or distant metastases. Six patients developed complications: 4 postoperative fractures (11%), 1 intra-articular loose body (3%) and 1 postoperative joint stiffness (3%). Anhydrous alcohol is a reasonable adjuvant for the curettage of low-grade chondrosarcoma of long bones. A long-term follow-up study is necessary, considering the slow biological progression of low-grade chondrosarcoma. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pharmaceutical policies in European countries.

Science.gov (United States)

Barros, Pedro Pita

2010-01-01

Pharmaceutical expenditures have an important role in Europe. The attempts to control expenditure have used a wide range of policy measures. We reviewed the main measures adopted by the European Union countries, especially in countries where governments are the largest third-party payers. To complement a literature review on the topic, data was gathered from national reviews of health systems and direct inquiries to several government bodies. Almost all countries regulate prices of pharmaceutical products. Popular policy measures include international referencing to set prices (using as benchmark countries that have set lower prices), internal reference pricing systems to promote price competition in domestic markets, and positive lists for reimbursement to promote consumption of generics (including in some cases substitution by pharmacists of drugs prescribed by physicians). Despite the wide range of policy measures, it is not possible to identify a "silver bullet" to control pharmaceutical expenditures. We also identified two main policy challenges: policy coordination among countries within the European Union to maintain incentives for R&D at the global level, and the development of new relationships with the pharmaceutical industry; namely, the so-called risk-sharing agreements between the pharmaceutical industry and governments/regulators (or large third-party payers).

Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial

Science.gov (United States)

Holmes, Eileen; Baselga, José; de Azambuja, Evandro; Dueck, Amylou C.; Viale, Giuseppe; Zujewski, Jo Anne; Goldhirsch, Aron; Armour, Alison; Pritchard, Kathleen I.; McCullough, Ann E.; Dolci, Stella; McFadden, Eleanor; Holmes, Andrew P.; Tonghua, Liu; Eidtmann, Holger; Dinh, Phuong; Di Cosimo, Serena; Harbeck, Nadia; Tjulandin, Sergei; Im, Young-Hyuck; Huang, Chiun-Sheng; Diéras, Véronique; Hillman, David W.; Wolff, Antonio C.; Jackisch, Christian; Lang, Istvan; Untch, Michael; Smith, Ian; Boyle, Frances; Xu, Binghe; Gomez, Henry; Suter, Thomas; Gelber, Richard D.; Perez, Edith A.

2016-01-01

Background Lapatinib (L) plus trastuzumab (T) improves outcomes for metastatic human epidermal growth factor 2–positive breast cancer and increases the pathologic complete response in the neoadjuvant setting, but their role as adjuvant therapy remains uncertain. Methods In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial, patients with centrally confirmed human epidermal growth factor 2–positive early breast cancer were randomly assigned to 1 year of adjuvant therapy with T, L, their sequence (T→L), or their combination (L+T). The primary end point was disease-free survival (DFS), with 850 events required for 80% power to detect a hazard ratio (HR) of 0.8 for L+T versus T. Results Between June 2007 and July 2011, 8,381 patients were enrolled. In 2011, due to futility to demonstrate noninferiority of L versus T, the L arm was closed, and patients free of disease were offered adjuvant T. A protocol modification required P ≤ .025 for the two remaining pairwise comparisons. At a protocol-specified analysis with a median follow-up of 4.5 years, a 16% reduction in the DFS hazard rate was observed with L+T compared with T (555 DFS events; HR, 0.84; 97.5% CI, 0.70 to 1.02; P = .048), and a 4% reduction was observed with T→L compared with T (HR, 0.96; 97.5% CI, 0.80 to 1.15; P = .61). L-treated patients experienced more diarrhea, cutaneous rash, and hepatic toxicity compared with T-treated patients. The incidence of cardiac toxicity was low in all treatment arms. Conclusion Adjuvant treatment that includes L did not significantly improve DFS compared with T alone and added toxicity. One year of adjuvant T remains standard of care. PMID:26598744

Multi-institutional Pooled Analysis on Adjuvant Chemoradiation in Pancreatic Cancer

International Nuclear Information System (INIS)

Morganti, Alessio G.; Falconi, Massimo; Stiphout, Ruud G.P.M. van; Mattiucci, Gian-Carlo; Alfieri, Sergio; Calvo, Felipe A.; Dubois, Jean-Bernard; Fastner, Gerd; Herman, Joseph M.; Maidment, Bert W.; Miller, Robert C.; Regine, William F.; Reni, Michele; Sharma, Navesh K.; Ippolito, Edy

2014-01-01

Purpose: To determine the impact of chemoradiation therapy (CRT) on overall survival (OS) after resection of pancreatic adenocarcinoma. Methods and Materials: A multicenter retrospective review of 955 consecutive patients who underwent complete resection with macroscopically negative margins (R0-1) for invasive carcinoma (T1-4; N0-1; M0) of the pancreas was performed. Exclusion criteria included metastatic or unresectable disease at surgery, macroscopic residual disease (R2), treatment with intraoperative radiation therapy (IORT), and a histological diagnosis of no ductal carcinoma, or postoperative death (within 60 days of surgery). In all, 623 patients received postoperative radiation therapy (RT), 575 patients received concurrent chemotherapy (CT), and 462 patients received adjuvant CT. Results: Median follow-up was 21.0 months. Median OS after adjuvant CRT was 39.9 versus 24.8 months after no adjuvant CRT (P<.001) and 27.8 months after CT alone (P<.001). Five-year OS was 41.2% versus 24.8% with and without postoperative CRT, respectively. The positive impact of CRT was confirmed by multivariate analysis (hazard ratio [HR] = 0.72; confidence interval [CI], 0.60-0.87; P=.001). Adverse prognostic factors identified by multivariate analysis included the following: R1 resection (HR = 1.17; CI = 1.07-1.28; P<.001), higher pT stage (HR = 1.23; CI = 1.11-1.37; P<.001), positive lymph nodes (HR = 1.27; CI = 1.15-1.41; P<.001), and tumor diameter >20 mm (HR = 1.14; CI = 1.05-1.23; P=.002). Multivariate analysis also showed a better prognosis in patients treated in centers with >10 pancreatic resections per year (HR = 0.87; CI = 0.78-0.97; P=.014) Conclusion: This study represents the largest comparative study on adjuvant therapy in patients after resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CRT

Multi-institutional Pooled Analysis on Adjuvant Chemoradiation in Pancreatic Cancer

Energy Technology Data Exchange (ETDEWEB)

Morganti, Alessio G. [Department of Radiotherapy, Università Cattolica S. Cuore, Rome (Italy); Unit of Radiotherapy, Unit of General Oncology, Fondazione Giovanni Paolo II, Campobasso (Italy); Falconi, Massimo [Department of Surgery, University of Verona, Verona (Italy); Stiphout, Ruud G.P.M. van [Department of Radiation Oncology (MAASTRO), GROW, University Medical Centre Maastricht (Netherlands); Mattiucci, Gian-Carlo, E-mail: gcmattiucci@rm.unicatt.it [Department of Radiotherapy, Università Cattolica S. Cuore, Rome (Italy); Alfieri, Sergio [Department of Surgery, Università Cattolica S. Cuore, Rome (Italy); Calvo, Felipe A. [Department of Oncology, Hospital General Universitario Gregorio Marañón, Complutense University, Madrid (Spain); Dubois, Jean-Bernard [Département de Radiothérapie, CRLC, Montpellier Cedex (France); Fastner, Gerd [Department of Radiotherapy, PMU, Salzburg (Austria); Herman, Joseph M. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Maidment, Bert W. [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia (United States); Miller, Robert C. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Regine, William F. [Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (United States); Reni, Michele [Department of Oncology, S. Raffaele Scientific Institute, Milan (Italy); Sharma, Navesh K. [Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (United States); Ippolito, Edy [Department of Radiation Oncology, University Campus Biomedico, Roma (Italy); and others

2014-11-15

Purpose: To determine the impact of chemoradiation therapy (CRT) on overall survival (OS) after resection of pancreatic adenocarcinoma. Methods and Materials: A multicenter retrospective review of 955 consecutive patients who underwent complete resection with macroscopically negative margins (R0-1) for invasive carcinoma (T1-4; N0-1; M0) of the pancreas was performed. Exclusion criteria included metastatic or unresectable disease at surgery, macroscopic residual disease (R2), treatment with intraoperative radiation therapy (IORT), and a histological diagnosis of no ductal carcinoma, or postoperative death (within 60 days of surgery). In all, 623 patients received postoperative radiation therapy (RT), 575 patients received concurrent chemotherapy (CT), and 462 patients received adjuvant CT. Results: Median follow-up was 21.0 months. Median OS after adjuvant CRT was 39.9 versus 24.8 months after no adjuvant CRT (P<.001) and 27.8 months after CT alone (P<.001). Five-year OS was 41.2% versus 24.8% with and without postoperative CRT, respectively. The positive impact of CRT was confirmed by multivariate analysis (hazard ratio [HR] = 0.72; confidence interval [CI], 0.60-0.87; P=.001). Adverse prognostic factors identified by multivariate analysis included the following: R1 resection (HR = 1.17; CI = 1.07-1.28; P<.001), higher pT stage (HR = 1.23; CI = 1.11-1.37; P<.001), positive lymph nodes (HR = 1.27; CI = 1.15-1.41; P<.001), and tumor diameter >20 mm (HR = 1.14; CI = 1.05-1.23; P=.002). Multivariate analysis also showed a better prognosis in patients treated in centers with >10 pancreatic resections per year (HR = 0.87; CI = 0.78-0.97; P=.014) Conclusion: This study represents the largest comparative study on adjuvant therapy in patients after resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CRT.

Nanocrystals Technology for Pharmaceutical Science.

Science.gov (United States)

Cheng, Zhongyao; Lian, Yumei; Kamal, Zul; Ma, Xin; Chen, Jianjun; Zhou, Xinbo; Su, Jing; Qiu, Mingfeng

2018-05-17

Nanocrystals technology is a promising method for improving the dissolution rate and enhancing the bioavailability of poorly soluble drugs. In recent years, it has been developing rapidly and applied to drug research and engineering. Nanocrystal drugs can be formulated into various dosage forms. This review mainly focused on the nanocrystals technology and its application in pharmaceutical science. Firstly, different preparation methods of nanocrystal technology and the characterization of nanocrystal drugs are briefly described. Secondly, the application of nanocrystals technology in pharmaceutical science is mainly discussed followed by the introduction of sustained release formulations. Then, the scaling up process, marketed nanocrystal drug products and regulatory aspects about nanodrugs are summarized. Finally, the specific challenges and opportunities of nanocrystals technology for pharmaceutical science are summarized and discussed. This review will provide a comprehensive guide for scientists and engineers in the field of pharmaceutical science and biochemical engineering. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

EU pharmaceutical expenditure forecast

OpenAIRE

Urbinati, Duccio; Rémuzat, Cécile; Kornfeld, Åsa; Vataire, Anne-Lise; Cetinsoy, Laurent; Aballéa, Samuel; Mzoughi, Olfa; Toumi, Mondher

2014-01-01

Background and Objectives: With constant incentives for healthcare payers to contain their pharmaceutical budgets, forecasting has become critically important. Some countries have, for instance, developed pharmaceutical horizon scanning units. The objective of this project was to build a model to assess the net effect of the entrance of new patented medicinal products versus medicinal products going off-patent, with a defined forecast horizon, on selected European Union (EU) Member States’ ph...

Immunogenicity, protective efficacy and mechanism of novel CCS adjuvanted influenza vaccine.

Science.gov (United States)

Even-Or, Orli; Samira, Sarit; Rochlin, Eli; Balasingam, Shobana; Mann, Alex J; Lambkin-Williams, Rob; Spira, Jack; Goldwaser, Itzhak; Ellis, Ronald; Barenholz, Yechezkel

2010-09-07

We optimized the immunogenicity of adjuvanted seasonal influenza vaccine based on commercial split influenza virus as an antigen (hemagglutinin = HA) and on a novel polycationic liposome as a potent adjuvant and efficient antigen carrier (CCS/C-HA vaccine). The vaccine was characterized physicochemically, and the mechanism of action of CCS/C as antigen carrier and adjuvant was studied. The optimized CCS/C-HA split virus vaccine, when administered intramuscularly (i.m.), is significantly more immunogenic in mice, rats and ferrets than split virus HA vaccine alone, and it provides for protective immunity in ferrets and mice against live virus challenge that exceeds the degree of efficacy of the split virus vaccine. Similar adjuvant effects of optimized CCS/C are also observed in mice for H1N1 swine influenza antigen. The CCS/C-HA vaccine enhances immune responses via the Th1 and Th2 pathways, and it increases both the humoral responses and the production of IL-2 and IFN-γ but not of the pro-inflammatory factor TNFα. In mice, levels of CD4(+) and CD8(+) T-cells and of MHC II and CD40 co-stimulatory molecules are also elevated. Structure-function relationship studies of the CCS molecule as an adjuvant/carrier show that replacing the saturated palmitoyl acyl chain with the mono-unsaturated oleoyl (C18:1) chain affects neither size distribution and zeta potential nor immune responses in mice. However, replacing the polyalkylamine head group spermine (having two secondary amines) with spermidine (having only one secondary amine) reduces the enhancement of the immune response by ∼ 50%, while polyalkylamines by themselves are ineffective in improving the immunogenicity over the commercial HA vaccine. This highlights the importance of the particulate nature of the carrier and the polyalkylamine secondary amines in the enhancement of the immune responses against seasonal influenza. Altogether, our results suggest that the CCS/C polycationic liposomes combine the

Elucidating the mechanisms of protein antigen adsorption to the CAF/NAF liposomal vaccine adjuvant systems

DEFF Research Database (Denmark)

Hamborg, Mette; Rose, Fabrice; Jorgensen, Lene

2014-01-01

is generally known about how antigens and adjuvants interact at the molecular level. The aim of this study was to elucidate the mechanisms of interactions between the equally sized, but oppositely charged model protein antigens α-lactalbumin and lysozyme, and i) the clinically tested cationic liposomal...... antigens are presented to antigen-presenting cells, and may play an important role for the efficacy of the vaccine-induced immune response. These studies thus exemplify the importance of characterizing the molecular interactions between the vaccine antigen and adjuvant along with immunogenicity......The reverse vaccinology approach has recently resulted in the identification of promising protein antigens, which in combination with appropriate adjuvants can stimulate customized, protective immune responses. Although antigen adsorption to adjuvants influences vaccine efficacy and safety, little...

Nanotechnology tools in pharmaceutical R&D

OpenAIRE

Challa S.S.R. Kumar

2010-01-01

Nanotechnology is a new approach to problem solving and can be considered as a collection of tools and ideas which can be applied in pharmaceutical industry. Application of nanotechnology tools in pharmaceutical R&D is likely to result in moving the industry from ‘blockbuster drug’ model to ‘personalized medicine’. There are compelling applications in pharmaceutical industry where inexpensive nanotechnology tools can be utilized. The review explores the possibility of categorizing various nan...

Adjuvant therapy in renal cell carcinoma: does higher risk for recurrence improve the chance for success?

Science.gov (United States)

Figlin, R A; Leibovich, B C; Stewart, G D; Negrier, S

2018-02-01

The success of targeted therapies, including inhibitors of the vascular endothelial growth factor pathway or the mammalian target of rapamycin, in the treatment of metastatic renal cell carcinoma led to interest in testing their efficacy in the adjuvant setting. Results from the first trials are now available, with other studies due to report imminently. This review provides an overview of adjuvant targeted therapy in renal cell carcinoma, including interpretation of currently available conflicting data and future direction of research. We discuss the key differences between the completed targeted therapy adjuvant trials, and highlight the importance of accurately identifying patients who are likely to benefit from adjuvant treatment. We also consider reasons why blinded independent radiology review and treatment dose may prove critical for adjuvant treatment success. The implications of using disease-free survival as a surrogate end point for overall survival from the patient perspective and measurement of health benefit have recently been brought into focus and are discussed. Finally, we discuss how the ongoing adjuvant trials with targeted therapies and checkpoint inhibitors may improve our understanding and ability to prevent tumor recurrence after nephrectomy in the future.

Patent indicators: a window to pharmaceutical market success.

Science.gov (United States)

Guo, Yang; Hu, Yuanjia; Zheng, Mingli; Wang, Yitao

2013-07-01

Pharmaceutical success in the market is the best reward for pharmaceutical investors undergoing the lengthy, costly and risky process of pharmaceutical Research and Development (R&D). Drugs with high market revenues trigger fierce competition between pharmaceutical enterprises, as is demonstrated by the increasing Mergers & Acquisitions (M&A) cases focusing on seizing the best-selling products. On the other hand, patents, as the best shield for innovative drugs against generic drugs, become a powerful weapon for pharmaceutical enterprises to win the substantial returns generated by market exclusivity. Patents seem to be directly responsible for the commercial success of new medicines. In this context, it is of great significance to find out the empirical associations between pharmaceutical commercial success and patents. By comprehensively analysing 127 drugs marketed in the USA and their 621 American patents, this article identifies the evidence to link various patent indicators with pharmaceutical sales in actual market.

Tocotrienols are good adjuvants for developing cancer vaccines

Directory of Open Access Journals (Sweden)

Radhakrishnan Ammu

2010-01-01

Full Text Available Abstract Background Dendritic cells (DCs have the potential for cancer immunotherapy due to their ability to process and present antigens to T-cells and also in stimulating immune responses. However, DC-based vaccines have only exhibited minimal effectiveness against established tumours in mice and humans. The use of appropriate adjuvant enhances the efficacy of DC based cancer vaccines in treating tumours. Methods In this study we have used tocotrienol-rich fraction (TRF, a non-toxic natural compound, as an adjuvant to enhance the effectiveness of DC vaccines in treating mouse mammary cancers. In the mouse model, six-week-old female BALB/c mice were injected subcutaneously with DC and supplemented with oral TRF daily (DC+TRF and DC pulsed with tumour lysate from 4T1 cells (DC+TL. Experimental mice were also injected with DC pulsed with tumour lysate and supplemented daily with oral TRF (DC+TL+TRF while two groups of animal which were supplemented daily with carrier oil (control and with TRF (TRF. After three times vaccination, mice were inoculated with 4T1 cells in the mammary breast pad to induce tumour. Results Our study showed that TRF in combination with DC pulsed with tumour lysate (DC+TL+TRF injected subcutaneously significantly inhibited the growth of 4T1 mammary tumour cells as compared to control group. Analysis of cytokines production from murine splenocytes showed significant increased productions of IFN-γ and IL-12 in experimental mice (DC+TL+TRF compared to control, mice injected with DC without TRF, mice injected with DC pulsed with tumour lysate and mice supplemented with TRF alone. Higher numbers of cytotoxic T cells (CD8 and natural killer cells (NK were observed in the peripheral blood of TRF adjuvanted DC pulsed tumour lysate mice. Conclusion Our study show that TRF has the potential to be an adjuvant to augment DC based immunotherapy.

Retroperitoneal liposarcoma; The role of adjuvant radiation therapy and the prognostic factors

Energy Technology Data Exchange (ETDEWEB)

Lee, Hong Seok; Yu, Jeong Il; Lim, Do Hoon; Kim, Sung Joo [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2016-09-15

To evaluate the benefit of adjuvant radiation therapy (RT) for retroperitoneal liposarcoma (RPLS) following gross tumor removal. We reviewed 77 patients with primary RPLS surgically treated between January 2000 and December 2013. Cases with gross residual disease were excluded. Tumor grade was evaluated according to the French Federation of Cancer Centers Sarcoma Group (FNCLCC) system. Adjuvant RT was delivered to 32 patients (42%) using external beam RT alone. Median follow-up time was 36 months (range, 5 to 169). Among 77 patients, 33 (43%) presented with well-differentiated, 31 (40%) with de-differentiated, 8 (10%) with myxoid/round and 4 (5%) with pleomorphic morphology. The RT group included less well-differentiated subtype than surgery group (28% vs. 53%). During follow up, 34 patients (44%) showed local recurrence. Local recurrence rate was lower in the RT group (38%) compared to the surgery group (49%). The 3-year local control rate (LC) was 55.6%, and the 3-year overall survival (OS) was 82.1%. Tumor histology and FNCLCC grade were significantly associated with local recurrence. There was no statistical significance of adding adjuvant RT in LC (p = 0.312). However, patients with tumor histology other than well-differentiated subtype showed marginally decreased local recurrence rate after adjuvant RT (3-year LC, RT 43.9% vs. no RT 35.3%; p = 0.087). RPLS patients receiving RT experienced less local recurrence. We suggest that the addition of adjuvant RT may be related to improvement of LCs, especially in patients with non-favorable histologic subtypes.

21 CFR 178.3010 - Adjuvant substances used in the manufacture of foamed plastics.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Adjuvant substances used in the manufacture of... substances used in the manufacture of foamed plastics. The following substances may be safely used as adjuvants in the manufacture of foamed plastics intended for use in contact with food, subject to any...

Silica nanoparticles as the adjuvant for the immunisation of mice using hepatitis B core virus-like particles.

Directory of Open Access Journals (Sweden)

Dace Skrastina

Full Text Available Advances in nanotechnology and nanomaterials have facilitated the development of silicon dioxide, or Silica, particles as a promising immunological adjuvant for the generation of novel prophylactic and therapeutic vaccines. In the present study, we have compared the adjuvanting potential of commercially available Silica nanoparticles (initial particles size of 10-20 nm with that of aluminium hydroxide, or Alum, as well as that of complete and incomplete Freund's adjuvants for the immunisation of BALB/c mice with virus-like particles (VLPs formed by recombinant full-length Hepatitis B virus core (HBc protein. The induction of B-cell and T-cell responses was studied after immunisation. Silica nanoparticles were able to adsorb maximally 40% of the added HBc, whereas the adsorption capacity of Alum exceeded 90% at the same VLPs/adjuvant ratio. Both Silica and Alum formed large complexes with HBc VLPs that sedimented rapidly after formulation, as detected by dynamic light scattering, spectrophotometry, and electron microscopy. Both Silica and Alum augmented the humoral response against HBc VLPs to the high anti-HBc level in the case of intraperitoneal immunisation, whereas in subcutaneous immunisation, the Silica-adjuvanted anti-HBc level even exceeded the level adjuvanted by Alum. The adjuvanting of HBc VLPs by Silica resulted in the same typical IgG2a/IgG1 ratios as in the case of the adjuvanting by Alum. The combination of Silica with monophosphoryl lipid A (MPL led to the same enhancement of the HBc-specific T-cell induction as in the case of the Alum and MPL combination. These findings demonstrate that Silica is not a weaker putative adjuvant than Alum for induction of B-cell and T-cell responses against recombinant HBc VLPs. This finding may have an essential impact on the development of the set of Silica-adjuvanted vaccines based on a long list of HBc-derived virus-like particles as the biological component.

Archives: Tropical Journal of Pharmaceutical Research

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Archives: Nigerian Journal of Pharmaceutical Research

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Pharmaceutical technology management--profitable business avenue.

Science.gov (United States)

Puthli, Shivanand P

2010-01-01

Growing research expenditure, regulatory framework and generic erosion have forced pharmaceutical companies globally to resort to pharmaceutical technology management (PTM). Indeed, the pharmaceutical industry has witnessed the impact of innovative drug delivery and device technologies and their influence on business. PTM has given a new business insight with greater profits and enhancement of product franchise. Promising breakthrough technologies have not been able to reach a commercial platform largely owing to lack of capital at the preliminary stages of the product development program. Intellectual property plays a considerable role in protecting innovative technologies. Joint ventures and strategic alliances also become important for commercializing a new technology. The synergy of PTM with options of in-licensing is expected to infuse newer opportunities to the pharmaceutical business.

Pharmaceutical care education in Kuwait: pharmacy students’ perspectives

OpenAIRE

Katoue, Maram G.; Awad, Abdelmoneim I.; Schwinghammer, Terry L.; Kombian, Samuel B.

2014-01-01

Background: Pharmaceutical care is defined as the responsible provision of medication therapy to achieve definite outcomes that improve patients’ quality of life. Pharmacy education should equip students with the knowledge, skills, and attitudes they need to practise pharmaceutical care competently. Objective: To investigate pharmacy students’ attitudes towards pharmaceutical care, perceptions of their preparedness to perform pharmaceutical care competencies, opinions about the importance...

Saponin-based adjuvants induce cross-presentation in dendritic cells by intracellular lipid body formation

NARCIS (Netherlands)

Brok, M.H. den; Bull, C.; Wassink, M.; Graaf, A.M.A. de; Wagenaars, J.A.L.; Minderman, M.; Thakur, M.; Amigorena, S.; Rijke, E.O.; Schrier, C.C.; Adema, G.J.

2016-01-01

Saponin-based adjuvants (SBAs) are being used in animal and human (cancer) vaccines, as they induce protective cellular immunity. Their adjuvant potency is a factor of inflammasome activation and enhanced antigen cross-presentation by dendritic cells (DCs), but how antigen cross-presentation is

Vulnerabilities to misinformation in online pharmaceutical marketing

Science.gov (United States)

De Freitas, Julian; Falls, Brian A; Haque, Omar S; Bursztajn, Harold J

2013-01-01

Given the large percentage of Internet users who search for health information online, pharmaceutical companies have invested significantly in online marketing of their products. Although online pharmaceutical marketing can potentially benefit both physicians and patients, it can also harm these groups by misleading them. Indeed, some pharmaceutical companies have been guilty of undue influence, which has threatened public health and trust. We conducted a review of the available literature on online pharmaceutical marketing, undue influence and the psychology of decision-making, in order to identify factors that contribute to Internet users’ vulnerability to online pharmaceutical misinformation. We find five converging factors: Internet dependence, excessive trust in the veracity of online information, unawareness of pharmaceutical company influence, social isolation and detail fixation. As the Internet continues to change, it is important that regulators keep in mind not only misinformation that surrounds new web technologies and their contents, but also the factors that make Internet users vulnerable to misinformation in the first place. Psychological components are a critical, although often neglected, risk factor for Internet users becoming misinformed upon exposure to online pharmaceutical marketing. Awareness of these psychological factors may help Internet users attentively and safely navigate an evolving web terrain. PMID:23761527

Pharmaceutical costs of assisted reproduction in Spain.

Science.gov (United States)

Lorente, Maria-Reyes; Hernández, Juana; Antoñanzas, Fernando

2013-11-01

Assisted reproduction is one of the health services currently being considered for possible limitation or exclusion from the public health services portfolio in Spain. One of the main reasons claimed for this is the impact on the budget for pharmaceutical expenditure. The objective of this study was to assess the significance of the pharmaceutical costs of assisted reproduction in Spain. This study focused on medical practice in Spain, and is based on the opinions of experts in assisted reproduction and the results provided by professional societies' publications. The reference year is 2012 and the setting was secondary care. We have included all existing pharmaceutical modalities for assisted reproduction, as well as the most common drug for each modality. We have considered the pharmaceutical cost per cycle for artificial insemination, in vitro fertilisation with or without intracytoplasmic sperm injection (IVF_ICSI), and cryotransfer and donated fresh oocytes reception. In Spain, artificial insemination has a pharmaceutical cost per cycle of between €69.36 and €873.79. This amounts to an average cycle cost of €364.87 for partner's sperm and €327.10 for donor sperm. The pharmaceutical cost of IVF_ICSI ranges between €278.16 and €1,902.66, giving an average cost per cycle of €1,139.65. In the case of cryotransfer and donated fresh oocytes reception, the pharmaceutical cost per cycle is between €22.61 and €58.73, yielding an average cost of €40.67. The budgetary impact of pharmaceutical expenditure for assisted reproduction in Spain for the year 2012 was estimated at €98.7 million. In Spain, the total pharmaceutical cost of assisted reproduction is substantial. According to our results, we can say that about 29% of the total pharmaceutical expenditure for assisted reproduction techniques is funded by the National Health System and the rest represents 2.4% of the total annual out-of-pocket family expenditure on drugs.

Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Clinical Practice Guideline Focused Update.

Science.gov (United States)

Denduluri, Neelima; Chavez-MacGregor, Mariana; Telli, Melinda L; Eisen, Andrea; Graff, Stephanie L; Hassett, Michael J; Holloway, Jamie N; Hurria, Arti; King, Tari A; Lyman, Gary H; Partridge, Ann H; Somerfield, Mark R; Trudeau, Maureen E; Wolff, Antonio C; Giordano, Sharon H

2018-05-22

Purpose To update key recommendations of the ASCO guideline adaptation of the Cancer Care Ontario guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer and adjuvant targeted therapy for breast cancer. Methods An Expert Panel conducted targeted systematic literature reviews guided by a signals approach to identify new, potentially practice-changing data that might translate to revised practice recommendations. Results The Expert Panel reviewed phase III trials that evaluated adjuvant capecitabine after completion of standard preoperative anthracycline- and taxane-based combination chemotherapy by patients with early-stage breast cancer HER2-negative breast cancer with residual invasive disease at surgery; the addition of 1 year of adjuvant pertuzumab to combination chemotherapy and trastuzumab for patients with early-stage, HER2-positive breast cancer; and the use of neratinib as extended adjuvant therapy for patients after combination chemotherapy and trastuzumab-based adjuvant therapy with early-stage, HER2-positive breast cancer. Recommendations Patients with early-stage HER2-negative breast cancer with pathologic, invasive residual disease at surgery following standard anthracycline- and taxane-based preoperative therapy may be offered up to six to eight cycles of adjuvant capecitabine. Clinicians may add 1 year of adjuvant pertuzumab to trastuzumab-based combination chemotherapy in patients with high-risk, early-stage, HER2-positive breast cancer. Clinicians may use extended adjuvant therapy with neratinib to follow trastuzumab in patients with early-stage, HER2-positive breast cancer. Neratinib causes substantial diarrhea, and diarrhea prophylaxis must be used. Additional information can be found at www.asco.org/breast-cancer-guidelines .

in vivo evaluation of chitosan as an adjuvant in subcutaneous vaccine formulations

DEFF Research Database (Denmark)

Scherließ, Regina; Buske, Simon; Young, Katherine

2013-01-01

Vaccines utilising pure antigens instead of whole pathogens and alternative administration routes require the use of potent adjuvants and effective antigen delivery systems. Chitosan has been reported to act as both an adjuvant as well as a matrix for delivery systems. Chitosan is a natural product...... produced predominantly from crab shell and commercially available preparations vary in molecular weight, degree of deacetylation and purity. In this study, the impact of chitosan characteristics (molecular weight, degree of deacetylation, particle size, viscosity and impurities) on adjuvant activity were...... examined. It could be shown that the degree of immune response differed if different chitosan qualities were used and this could be attributed to different characteristics of the chitosan qualities: the immunoadjuvant effect of chitosan probably is a result of an interplay between chemical properties...

Pharmaceutical policy and the pharmacy profession

DEFF Research Database (Denmark)

Traulsen, Janine Marie; Almarsdóttir, Anna Birna

2005-01-01

In this article, the authors look at the relationship between pharmaceutical policy and the pharmacy profession with focus on pharmacy practice and pharmacists in the health care sector. Pharmaceutical policy encompasses three major policy inputs: public health policy, health care policy and indu......In this article, the authors look at the relationship between pharmaceutical policy and the pharmacy profession with focus on pharmacy practice and pharmacists in the health care sector. Pharmaceutical policy encompasses three major policy inputs: public health policy, health care policy...... and industrial policy. In order to analyse and understand pharmaceutical policy, it is important to know how policymakers view pharmacy and pharmacists. The authors look at the issues that arise when policy regulates pharmacy as a business, and what this means for the profession. The perspective of pharmacy...... in managerialism, and how the division of labour with other health professionals such as physicians and pharmacy assistants is affecting the pharmacy profession's position in the labour market. Next the authors look at ways in which the pharmacy profession has affected policy. Pharmacists have been instrumental...

Utilization of a Green Brominating Agent for the Spectrophotometric Determination of Pipazethate HCl in Pure Form and Pharmaceutical Preparations

Directory of Open Access Journals (Sweden)

Ayman A. Gouda

2013-01-01

Full Text Available Five simple, accurate, and sensitive spectrophotometric methods (A–E have been described for the indirect assay of pipazethate HCl (PZT either in pure form or in pharmaceutical preparations. The proposed methods are based on the bromination of pipazethate HCl with a solution of excess bromate-bromide mixture in hydrochloric acid medium and subsequent estimation of the residual bromine by different reaction schemes. In the first three methods (A–C, the determination of the residual bromine is based on its ability to bleach the color of methyl orange, indigo carmine, or thymol blue dyes and measuring the absorbance at 520, 610, and 550 nm for methods A, B, and C, respectively. Methods D and E involves treating the unreacted bromine with a measured excess of iron(II, and the remaining iron(II is complexed with 1,10-phenanthroline, and the increase in absorbance is measured at 510 nm for method D and the resulting iron(III is complexed with thiocyanate and the absorbance is measured at 480 nm for method E. The different experimental parameters affecting the development and stability of the color are carefully studied and optimized. Regression analysis of the Beer-Lambert plots showed good correlation in the concentration ranges of 0.5–8.0 μg . The apparent molar absorptivity, Sandell's sensitivity, detection and quantitation limits were evaluated. The proposed methods have been applied and validated successfully for the analysis of the drug in its pure form and pharmaceutical formulations with mean recoveries of 99.94%–100.15% and relative standard deviation ≤1.53. No interference was observed from a common pharmaceutical adjuvant. Statistical comparison of the results with the reference method shows excellent agreement and indicates no significant difference in accuracy and precision.

Pharmaceuticals: pharmaceutical cost controls--2005. End of Year Issue Brief.

Science.gov (United States)

Seay, Melicia; Varma, Priya

2005-12-31

The enactment of the Omnibus Budget Reconciliation Act of 1990 (OBRA '90) gave states the option of offering pharmaceutical benefits within their Medicaid programs. But the law placed restrictions on states' flexibility to control what prescriptions they would cover and required the states to reimburse outpatient prescription drugs from manufacturers that signed rebate agreements with the U.S. Department of Health and Human Services. Forty-nine states--Arizona is excluded, based on its program structure--and the District of Columbia currently offer prescription drug coverage under the Medicaid Drug Rebate Program. During the past four years, states all over the country have been plagued with revenue shortfalls in their state Medicaid budgets. While the fiscal situation improved for most states in the 2004 legislative session, many states still face budget pressures in 2005. Compounding existing budget pressures are threats from the Bush Administration to shift increased costs of the Medicaid program on to the states. All things considered, the economic pressure of funding Medicaid is at the top of legislative agendas in 2005. As in previous years, states are attempting to reduce costs to their Medicaid programs by seeking savings in their pharmaceutical programs. Prescription drug costs are highly attributed as a contributing factor to the fiscal climate of state Medicaid programs. Currently, prescription drug spending outpaces that of every other category of health care and drug prices are rising faster than inflation. In response, states are instituting a variety of pharmaceutical cost control measures such as creating preferred drug lists (PDLs), negotiating supplemental rebates, forming bulk purchasing pools, promoting generic drug substitution and implementing price controls. As prescription drug cost containment tools have gained acceptance and momentum, they continue to be controversial. This issue brief explores the debate, history, methodology, utilization

Application of guar gum biopolymer in the prescription of tablets with sodium ibuprofen--quality tests and pharmaceutical availability in vitro.

Science.gov (United States)

Berner-Strzelczyk, Aneta; Kołodziejska, Justyna; Zgoda, Marian Mikołaj

2006-01-01

The increasing interest of the technology of drug form in natural biopolymers has become the reason for undertaking investigations on the possibility of guar gum application in the prescription of oral solid form of a drug. Alternative compositions and technology of the production of tablets of regulated in time sodium ibuprofen release were worked out for children. Two series of tablets were prepared with guar gum (5 and 10% content) and a series without the biopolymer. The tablet mass in each case contained keryostatic sorbitol and bioadhesive polyvinylpyrrolidone. All tablets were tested as regards the quality of production, compliance with the requirements of Polish Pharmacopoeia VI and potential therapeutic usefulness, manifestation of which is pharmaceutical availability of the therapeutic agent (sodium ibuprofen). The tests demonstrated that the produced tablets with sodium ibuprofen have proper physicochemical properties, in compliance with Polish Pharmacopoeia VI requirements. Application of biopolymer of guar gum type as adjuvant substance contributes to the improvement of the tablet hardness parameters and prevents technological problems (lining mixture of powders to tableting machine punch). The designed tablets demonstrate proper pharmaceutical availability of over 80%. Introduction of guar gum into their prescription prolonged their disintegration time and the rate of sodium ibuprofen release, which predisposes the produced form of a drug to have the function of a tablet with slowed-down release.

Pharmaceutical care education in Kuwait: pharmacy students' perspectives.

Science.gov (United States)

Katoue, Maram G; Awad, Abdelmoneim I; Schwinghammer, Terry L; Kombian, Samuel B

2014-07-01

Pharmaceutical care is defined as the responsible provision of medication therapy to achieve definite outcomes that improve patients' quality of life. Pharmacy education should equip students with the knowledge, skills, and attitudes they need to practise pharmaceutical care competently. To investigate pharmacy students' attitudes towards pharmaceutical care, perceptions of their preparedness to perform pharmaceutical care competencies, opinions about the importance of the various pharmaceutical care activities, and the barriers to its implementation in Kuwait. A descriptive, cross-sectional survey of pharmacy students (n=126) was conducted at Faculty of Pharmacy, Kuwait University. Data were collected via a pre-tested self-administered questionnaire. Descriptive statistics including percentages, medians and means Likert scale rating (SD) were calculated and compared using SPSS, version 19. Statistical significance was accepted at a p value of 0.05 or lower. The response rate was 99.2%. Pharmacy students expressed overall positive attitudes towards pharmaceutical care. They felt prepared to implement the various aspects of pharmaceutical care, with the least preparedness in the administrative/management aspects. Perceived pharmaceutical care competencies grew as students progressed through the curriculum. The students also appreciated the importance of the various pharmaceutical care competencies. They agreed/strongly agreed that the major barriers to the integration of pharmaceutical care into practice were lack of private counseling areas or inappropriate pharmacy layout (95.2%), lack of pharmacist time (83.3%), organizational obstacles (82.6%), and pharmacists' physical separation from patient care areas (82.6%). Pharmacy students' attitudes and perceived preparedness can serve as needs assessment tools to guide curricular change and improvement. Student pharmacists at Kuwait University understand and advocate implementation of pharmaceutical care while also

Pharmaceutical Cocrystals: Regulatory and Strategic Aspects, Design and Development

OpenAIRE

Gadade, Dipak Dilip; Pekamwar, Sanjay Sudhakar

2016-01-01

Cocrystal is a concept of the supramolecular chemistry which is gaining the extensive interest of researchers from pharmaceutical and chemical sciences and of drug regulatory agencies. The prominent reason of which is its ability to modify physicochemical properties of active pharmaceutical ingredients. During the development of the pharmaceutical product, formulators have to optimize the physicochemical properties of active pharmaceutical ingredients. Pharmaceutical cocrystals can be employe...

Effect of adjuvant chemotherapy in postmenopausal patients with invasive ductal versus lobular breast cancer.

Science.gov (United States)

Truin, W; Voogd, A C; Vreugdenhil, G; van der Heiden-van der Loo, M; Siesling, S; Roumen, R M

2012-11-01

On the basis of the lack of response of invasive lobular breast cancer to neoadjuvant chemotherapy, we questioned the effectiveness of adjuvant chemotherapy in relation to histology. Women with primary nonmetastatic invasive ductal or (mixed type) lobular breast cancer, aged 50-70 years, diagnosed between 1995 and 2008, were selected from the Netherlands Cancer Registry and followed until January 1, 2010. The patients were divided in two groups: one group receiving adjuvant hormonal therapy only and the other receiving adjuvant hormonal therapy in combination with adjuvant chemotherapy. In total, 19,609 patients had ductal cancer and 3685 had lobular cancer. The 10-year overall survival rate in ductal cancer when treated with hormonal therapy alone was 69%, compared with 74% with the combination therapy (P lobular cancer, 10-year survival rates were 68% after hormonal treatment alone and 66% after the combination therapy (P = 0.45). The hazard ratio (HR) for mortality in ductal cancer after combination therapy was 0.70 [95% confidence interval (CI) 0.64-0.76; P lobular cancer was 1.00 (95% CI 0.82-1.21; P = 0.97). Adjuvant chemotherapy seems to confer no additional beneficial effects in postmenopausal patients with pure or mixed type lobular breast cancer receiving hormonal therapy.

Biocatalytic Synthesis of Chiral Pharmaceutical Intermediates

Directory of Open Access Journals (Sweden)

Ramesh N. Patel

2004-01-01

Full Text Available The production of single enantiomers of drug intermediates has become increasingly important in the pharmaceutical industry. Chiral intermediates and fine chemicals are in high demand from both the pharmaceutical and agrochemical industries for the preparation of bulk drug substances and agricultural products. The enormous potential of microorganisms and enzymes for the transformation of synthetic chemicals with high chemo-, regio- and enantioselectivities has been demonstrated. In this article, biocatalytic processes are described for the synthesis of chiral pharmaceutical intermediates.

Pharmaceutical Cocrystals: Regulatory and Strategic Aspects, Design and Development

Directory of Open Access Journals (Sweden)

Dipak Dilip Gadade

2016-12-01

Full Text Available Cocrystal is a concept of the supramolecular chemistry which is gaining the extensive interest of researchers from pharmaceutical and chemical sciences and of drug regulatory agencies. The prominent reason of which is its ability to modify physicochemical properties of active pharmaceutical ingredients. During the development of the pharmaceutical product, formulators have to optimize the physicochemical properties of active pharmaceutical ingredients. Pharmaceutical cocrystals can be employed to improve vital physicochemical characteristics of a drug, including solubility, dissolution, bioavailability and stability of pharmaceutical compounds while maintaining its therapeutic activity. It is advantageous being a green synthesis approach for production of pharmaceutical compounds. The formation polymorphic forms, solvates, hydrates and salts of cocrystals during the synthesis reported in the literature which can be a potential issue in the development of pharmaceutical cocrystals. The approaches like hydrogen bonding rules, solubility parameters, screening through the CSD database or thermodynamic characteristics can be utilized for the rational design of cocrystals and selection of coformers for synthesis multi-component cocrystals. Considering the significance of pharmaceutical cocrystals pharmaceutical regulatory authorities in the United States and Europe issued guidance documents which may be helpful for pharmaceutical product registration in these regions. In this article, we deal with the design, synthesis, strategic aspects and characteristics of cocrystals along perspectives on its regulatory and intellectual property considerations.

Pharmaceutical Cocrystals: Regulatory and Strategic Aspects, Design and Development.

Science.gov (United States)

Gadade, Dipak Dilip; Pekamwar, Sanjay Sudhakar

2016-12-01

Cocrystal is a concept of the supramolecular chemistry which is gaining the extensive interest of researchers from pharmaceutical and chemical sciences and of drug regulatory agencies. The prominent reason of which is its ability to modify physicochemical properties of active pharmaceutical ingredients. During the development of the pharmaceutical product, formulators have to optimize the physicochemical properties of active pharmaceutical ingredients. Pharmaceutical cocrystals can be employed to improve vital physicochemical characteristics of a drug, including solubility, dissolution, bioavailability and stability of pharmaceutical compounds while maintaining its therapeutic activity. It is advantageous being a green synthesis approach for production of pharmaceutical compounds. The formation polymorphic forms, solvates, hydrates and salts of cocrystals during the synthesis reported in the literature which can be a potential issue in the development of pharmaceutical cocrystals. The approaches like hydrogen bonding rules, solubility parameters, screening through the CSD database or thermodynamic characteristics can be utilized for the rational design of cocrystals and selection of coformers for synthesis multi-component cocrystals. Considering the significance of pharmaceutical cocrystals pharmaceutical regulatory authorities in the United States and Europe issued guidance documents which may be helpful for pharmaceutical product registration in these regions. In this article, we deal with the design, synthesis, strategic aspects and characteristics of cocrystals along perspectives on its regulatory and intellectual property considerations.

Cognitive Changes After Adjuvant Treatment in Older Adults with Early-Stage Breast Cancer.

Science.gov (United States)

Lange, Marie; Heutte, Natacha; Noal, Sabine; Rigal, Olivier; Kurtz, Jean-Emmanuel; Lévy, Christelle; Allouache, Djelila; Rieux, Chantal; Lefel, Johan; Clarisse, Bénédicte; Leconte, Alexandra; Veyret, Corinne; Barthélémy, Philippe; Longato, Nadine; Tron, Laure; Castel, Hélène; Eustache, Francis; Giffard, Bénédicte; Joly, Florence

2018-06-22

Group-based trajectory modeling is particularly important to identify subgroups of patients with pathological cognitive changes after cancer treatment. To date, only one study has explored cognitive trajectories in older patients with cancer. The present article describes objective cognitive changes before to after adjuvant treatment in older adults with early-stage breast cancer (EBC) after adjuvant treatment compared with healthy controls. Participants were patients ≥65 years of age with newly diagnosed EBC and healthy controls (age-, sex-, and education-matched). The pretreatment assessment was conducted before adjuvant therapy, and the post-treatment assessment after the end of the first adjuvant treatment. Objective cognitive changes before to after treatment were evaluated based on the Reliable Change Index for cognitive decline accounting for cognitive impairment status. The sample consisted of women newly diagnosed with EBC ( n  = 118) and healthy controls ( n  = 62). Five patterns of changes before to after treatment were identified based on the presence of cognitive decline and cognitive impairment. The distribution of these five change patterns was statistically significant ( p  = .0001). Thirty-six percent of patients had phase shift changes, 31% without initial objective cognitive impairment developed impairment, 15% had a normal aging, 12% had a nonpathological decline, and 6% experienced accelerated cognitive decline. This study described for the first time objective cognitive changes before to after treatment of older adults with EBC immediately after the end of adjuvant treatment. A longer-term remote follow-up of adjuvant treatment is needed to better understand the cognitive trajectories of older patients with EBC. The Oncologist IMPLICATIONS FOR PRACTICE: After the end of adjuvant treatment, 31% of older adults with early-stage breast cancer without initial objective cognitive impairment developed impairment, and 6% experienced

Randomized Trial of Asprin as Adjuvant Therapy for Node-Positive Breast Cancer

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-15-1-0268 TITLE: Randomized Trial of Asprin as Adjuvant Therapy for Node-Positive Breast Cancer PRINCIPAL INVESTIGATOR...Eric Winer CONTRACTING ORGANIZATION: Dana-Farber Cancer Institute Boston, MA 02215 REPORT DATE: OCTOBER 2017 TYPE OF REPORT: ANNUAL PREPARED FOR...CONTRACT NUMBER Randomized Trial of Asprin as Adjuvant Therapy for Node- Positive Breast Cancer 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR

Liposomal preparations of muramyl glycopeptides as immunomodulators and adjuvants.

Science.gov (United States)

Turánek, Jaroslav; Ledvina, Miroslav; Kasná, Andrea; Vacek, Antonín; Hríbalova, Vera; Krejcí, Josef; Miller, Andrew D

2006-04-12

The need for safe and structurally defined immunomodulators and adjuvants is increasing in connection with the recently observed marked increase in the prevalence of pathological conditions characterized by immunodeficiency. Important groups of such compounds are muramyl glycopeptides, analogs of muramyl dipeptide (MDP), glucosaminyl-muramyl dipeptide (GMDP), and desmuramylpeptides. We have designed and synthesized new types of analogs with changes in both the sugar and the peptide parts of the molecule that show a high immunostimulating and adjuvant activity and suppressed adverse side effects. The introduction of lipophilic residues has also improved their incorporation into liposomes, which represent a suitable drug carrier. The proliposome-liposome method is based on the conversion of the initial proliposome preparation into liposome dispersion by dilution with the aqueous phase. The description of a home-made stirred thermostated cell and its link-up with a liquid delivery system for a rapid and automated preparation of multilamellar liposomes at strictly controlled conditions (sterility, temperature, dilution rate and schedule) is presented. The cell has been designed for laboratory-scale preparation of liposomes (300-1000 mg of phospholipid per run) in a procedure taking less than 90 min. The method can be readily scaled up. Examples of adjuvant and immunostimulatory effect of liposomal preparation in mice model will be presented.

Organic Colouring Agents in the Pharmaceutical Industry

Directory of Open Access Journals (Sweden)

Šuleková M.

2017-09-01

Full Text Available Food dyes are largely used in the process of manufacturing pharmaceutical products. The aim of such a procedure is not only to increase the attractiveness of products, but also to help patients distinguish between pharmaceuticals. Various dyes, especially organic colouring agents, may in some cases have a negative impact on the human body. They are incorporated into pharmaceutical products including tablets, hard gelatine capsules or soft gelatine capsules, lozenges, syrups, etc. This article provides an overview of the most widely used colouring agents in pharmaceuticals, their characteristics and the EU legislation which regulates their use.

Occurrence of pharmaceuticals in Taiwan's surface waters: impact of waste streams from hospitals and pharmaceutical production facilities.

Science.gov (United States)

Lin, Angela Yu-Chen; Tsai, Yu-Ting

2009-06-01

We investigated the occurrence and distribution of pharmaceuticals (including antibiotics, estrogens, non-steroidal anti-inflammatory drugs (NSAIDs), beta-blockers, and lipid regulators) in three rivers and in the waste streams of six hospitals and four pharmaceutical production facilities in Taiwan. The most frequently detected pharmaceuticals were acetaminophen, erythromycin-H(2)O, sulfamethoxazole, and gemfibrozil. NSAIDs were the next most-often detected compounds, with a detection frequency >60%. The other analytes were not detected or were seen in only a few samples at trace concentrations. The present study demonstrates a significant discharge of human medications from hospital and drug production facilities into surface waters in the Taipei district. The high concentrations of pharmaceuticals found in the Sindian and Dahan rivers demonstrate the alarming degree to which they have been impacted by urban drainage (waste effluents from hospitals, households, and pharmaceutical production facilities). The ubiquitous occurrence at extremely high concentrations of acetaminophen and erythromycin-H(2)O in both rivers (up to 15.7 and 75.5 microg/L) and in wastewater from hospitals and pharmaceutical production facilities (up to 417.5 and 7.84 microg/L) was unique. This finding, in combination with acetaminophen's status as the drug most often prescribed by Taiwan's dominant clinical institute, suggests the potential use of acetaminophen as a molecular indicator of contamination of Taiwan's aqueous environments with untreated urban drainage.

Insight into the cellular fate and toxicity of aluminium adjuvants used in clinically approved human vaccinations.

Science.gov (United States)

Mold, Matthew; Shardlow, Emma; Exley, Christopher

2016-08-12

Aluminium adjuvants remain the most widely used and effective adjuvants in vaccination and immunotherapy. Herein, the particle size distribution (PSD) of aluminium oxyhydroxide and aluminium hydroxyphosphate adjuvants was elucidated in attempt to correlate these properties with the biological responses observed post vaccination. Heightened solubility and potentially the generation of Al(3+) in the lysosomal environment were positively correlated with an increase in cell mortality in vitro, potentially generating a greater inflammatory response at the site of simulated injection. The cellular uptake of aluminium based adjuvants (ABAs) used in clinically approved vaccinations are compared to a commonly used experimental ABA, in an in vitro THP-1 cell model. Using lumogallion as a direct-fluorescent molecular probe for aluminium, complemented with transmission electron microscopy provides further insight into the morphology of internalised particulates, driven by the physicochemical variations of the ABAs investigated. We demonstrate that not all aluminium adjuvants are equal neither in terms of their physical properties nor their biological reactivity and potential toxicities both at the injection site and beyond. High loading of aluminium oxyhydroxide in the cytoplasm of THP-1 cells without immediate cytotoxicity might predispose this form of aluminium adjuvant to its subsequent transport throughout the body including access to the brain.

Does adjuvant systemic therapy with interferon-alpha for stage II-III melanoma prolong survival?

NARCIS (Netherlands)

Eggermont, Alexander M. M.; Punt, Cornelis J. A.

2003-01-01

The experience with interferon-alpha in malignant melanoma resembles, to some degree, the experience with various kinds of adjuvant immunotherapeutic agents where 25 years of phase III trials of adjuvant therapy in stage II-IIII melanoma have not defined a standard therapy. Most trials failed to

Adjuvant treatment or primary topical monotherapy for ocular surface squamous neoplasia: a systematic review

Directory of Open Access Journals (Sweden)

Gustavo Arruda Viani

Full Text Available ABSTRACT In this systematic review, we evaluated studies involving adjuvant and primary topical treatment for ocular surface squamous neoplasia (OSSN. The findings were: (i adjuvant 5-fluorouracil (5-FU reduces the risk of relapse after surgical excision with mild side effects [level Ib, grade of recommendation (GR A]. (ii Primary topical mitomycin (MMC produces a high rate of complete response, low recurrence rate, and mild side effects (level Ib, GR A. (iii Primary chemotherapy versus adjuvant chemotherapy produce similar rates of recurrence, with no significant difference (level IIb, GR B. (iv Adjuvant 5-FU versus MMC showed no significant differences, with mild side effects in both groups and a better toxicity profile for MMC (level III, GR C. (v Primary topical 5-FU versus MMC versus interferon (IFN showed similar rates of tumor recurrence, mild side effects for all drugs, and more severe side effects in the 5-FU arm, followed successively by MMC and IFN (level III, GR C.

Patrick Couvreur: inspiring pharmaceutical innovation.

Science.gov (United States)

Stanwix, Hannah

2014-05-01

Patrick Couvreur speaks to Hannah Stanwix, Managing Comissioning Editor: Professor Patrick Couvreur received his pharmacy degree from the Université Catholique de Louvain (Louvain-la-Neuve, Belgium) in 1972. He holds a PhD in pharmaceutical technology from the same university and completed a postdoctoral fellowship at the Eidgenössische Technische Hochschule (Zürich, Switzerland). Since 1984, Professor Couvreur has been Full Professor of Pharmacy at the Paris-Sud University (Paris, France) and was holder of the Chair of Innovation Technologique at the prestigious Collège de France (Paris, France). He has published more than 450 peer-reviewed articles and has an H-index of 73, with over 19,000 citations. Professor Coureur has been recognized by numerous national and international awards, including the 2004 Pharmaceutical Sciences World Congress Award, the prestigious Host Madsen Medal, the Prix Galien, the European Pharmaceutical Scientist Award 2011 from the European Federation of Pharmaceutical Sciences, the Médaille de l'Innovation from the Centre National de la Recherche Scientifique, and recently the European Inventor Award 2013 from the European Patent Office.

The short-term safety of adjuvant paclitaxel plus trastuzumab - A single centre experience.

Science.gov (United States)

Ates, Ozturk; Sunar, Veli; Aslan, Alma; Karatas, Fatih; Sahin, Suleyman; Altundag, Kadri

2017-01-01

HER2-amplified breast cancer (BC) has a poor prognosis. The combination of trastuzumab with chemotherapy in the adjuvant setting decreases recurrence and improves overall survival in HER2-positive BC. However, the role of adjuvant treatment in patients with HER2-amplified small BC without lymph node involvement is still under debate. The purpose of this study was to investigate the safety of adjuvant paclitaxel and trastuzumab (APT) in this group of patients. A total of 87 operated early BC patients without lymph node involvement (N0) were treated with APT for 12 weeks followed by trastuzumab alone for a total of 9 months. Clinicopathological features and adverse events were analyzed. The median patient age was 50 years (range 28- 82), and 51% of them were postmenopausal. The median tumor diameter was 2.4 cm (range 0.5-6), with 51% of the patients having tumor size between 2 and 3 cm. Eighty-one percent of patients had invasive ductal carcinoma (IDC), and 64% had grade 3 tumors. Adjuvant hormone therapy and adjuvant radiotherapy were administered to 65 and 54% of patients, respectively. At a median follow up of 13 months (range 6-38), one patient (1.1%, 95% CI 0-3.4) experienced an asymptomatic decrease in left ventricular ejection fraction (LVEF) and 3 patients (3.4%, 95% CI 0-6.9) experienced grade 3 neuropathy. APT appears to be a safe combination in early-stage, HER2-amplified and node-negative BC.

Biochemical Evaluation of Withania somnifera Root Powder on Adjuvant-Induced Arthritis in Rats

Directory of Open Access Journals (Sweden)

Mahaboobkhan Rasool

2015-04-01

Full Text Available The present investigation was carried out to evaluate the biochemical effect of Withania somnifera Linn. Solanaceae, commonly known as ashwagandha on adjuvant induced arthritic rats. Results were compared to Indomethacin, a non steroidal anti-inflammatory drug. Arthritis was induced by an intra dermal injection of Complete Freund’s Adjuvant (0.1 ml into the right hind paw of Wistar albino rats. Withania somnifera root powder (1000 mg/kg/day and Indomethacin (3 mg/kg/day were orally administered for 8 days (from 11th to 18th day after adjuvant injection. After the experimental period, all the animals were sacrificed and serum, liver and spleen samples were collected for further biochemical analysis. A significant increase in the activities of gluconeogenic enzymes, tissue marker enzymes, blood glucose level, WBC, platelet count, erythrocyte sedimentation rate, and acute phase proteins (hyaluronic acid, fibrinogen and ceruloplasmin was observed in adjuvant-induced arthritic rats, whereas the activities of glycolytic enzymes, body weight, levels of hemoglobin, RBC count, and packed cell volume were found to be decreased. These biochemical alterations observed in arthritic animals were ameliorated significantly after the administration of Withania somnifera root powder (1000 mg/kg/b.wt and Indomethacin (3 mg/kg/b.wt. Our results suggest that Withania somnifera root powder is capable of rectifying the above biochemical changes in adjuvant arthritis and it may prove to be useful in treating rheumatoid arthritis.

Preclinical Evaluation of the Synthetic Adjuvant SQS-21 and its Constituent Isomeric Saponins

Science.gov (United States)

Ragupathi, Govind; Damani, Payal; Deng, Kai; Adams, Michelle M.; Hang, Jianfeng; George, Constantine; Livingston, Philip O.; Gin, David Y.

2010-01-01

The saponin fraction QS-21 from Quillaja saponaria has been demonstrated to be a potent immunological adjuvant when mixed with keyhole limpet hemocyanin conjugate vaccines, as well as with other classes of subunit antigen vaccines. QS-21 adjuvant is composed of two isomers that include the apiose and xylose forms in a ratio of 65:35, respectively. The chemical syntheses of these two isomers in pure form have recently been disclosed. Herein we describe detailed in vivo immunological evaluations of these synthetic QS-21 isomeric constituents, employing the GD3-KLH melanoma antigen. With this vaccine construct, high antibody titers against GD3 ganglioside and KLH were elicited when GD3-KLH was co-administered with adjuvant, either as the individual separate synthetic QS-21 isomers (SQS-21-Api or SQS-21-Xyl), or as its reconstituted 65:35 isomeric mixture (SQS-21). These antibody titer levels were comparable to that elicited by vaccinations employing naturally derived QS-21 (PQS-21). Moreover, toxicities of the synthetic saponin adjuvants were also found to be comparable to that of naturally derived PQS-21. These findings demonstrate unequivocally that the adjuvant activity of QS-21 resides in these two principal isomeric forms, and not in trace contaminants within the natural extracts. This lays the foundation for future exploration of structure-function correlations to enable the discovery of novel saponins with increased potency, enhanced stability, and attenuated toxicity. PMID:20450868

Advax™, a novel microcrystalline polysaccharide particle engineered from delta inulin, provides robust adjuvant potency together with tolerability and safety.

Science.gov (United States)

Petrovsky, Nikolai; Cooper, Peter D

2015-11-04

There is an ongoing need for new adjuvants to facilitate development of vaccines against HIV, tuberculosis, malaria and cancer, amongst many others. Unfortunately, the most potent adjuvants are often associated with toxicity and safety issues. Inulin, a plant-derived polysaccharide, has no immunological activity in its native soluble form but when crystallized into a stable microcrystalline particulate from (delta inulin) acquires potent adjuvant activity. Delta inulin has been shown to enhance humoral and cellular immune responses against a broad range of co-administered viral, bacterial, parasitic and toxin antigens. Inulin normally crystallizes as large heterogeneous particles with a broad size distribution and variable solubility temperatures. To ensure reproducible delta inulin particles with a consistent size distribution and temperature of solubility, a current Good Manufacturing Practice (cGMP) process was designed to produce Advax™ adjuvant. In its cCMP form, Advax™ adjuvant has proved successful in human trials of vaccines against seasonal and pandemic influenza, hepatitis B and insect sting anaphylaxis, enhancing antibody and T-cell responses while being safe and well tolerated. Advax™ adjuvant represents a novel human adjuvant that enhances both humoral and cellular immunity. This review describes the discovery and development of Advax™ adjuvant and research into its unique mechanism of action. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rotavirus capsid VP6 tubular and spherical nanostructures act as local adjuvants when co-delivered with norovirus VLPs.

Science.gov (United States)

Malm, M; Heinimäki, S; Vesikari, T; Blazevic, V

2017-09-01

A subunit protein vaccine candidate based on norovirus (NoV) virus-like particles (VLPs) and rotavirus (RV) VP6 protein against acute childhood gastroenteritis has been proposed recently. RV VP6 forms different oligomeric nanostructures, including tubes and spheres when expressed in vitro, which are highly immunogenic in different animal models. We have shown recently that recombinant VP6 nanotubes have an adjuvant effect on immunogenicity of NoV VLPs in mice. In this study, we investigated if the adjuvant effect is dependent upon a VP6 dose or different VP6 structural assemblies. In addition, local and systemic adjuvant effects as well as requirements for antigen co-delivery and co-localization were studied. The magnitude and functionality of NoV GII.4-specific antibodies and T cell responses were tested in mice immunized with GII.4 VLPs alone or different combinations of VLPs and VP6. A VP6 dose-dependent adjuvant effect on GII.4-specific antibody responses was observed. The adjuvant effect was found to be strictly dependent upon co-administration of NoV GII.4 VLPs and VP6 at the same anatomic site and at the same time. However, the adjuvant effect was not dependent on the types of oligomers used, as both nanotubes and nanospheres exerted adjuvant effect on GII.4-specific antibody generation and, for the first time, T cell immunity. These findings elucidate the mechanisms of VP6 adjuvant effect in vivo and support its use as an adjuvant in a combination NoV and RV vaccine. © 2017 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.

Prognostic impact of interhospital variation in adjuvant chemotherapy for patients with Stage II/III colorectal cancer: a nationwide study.

Science.gov (United States)

Arakawa, K; Kawai, K; Tanaka, T; Hata, K; Sugihara, K; Nozawa, H

2018-05-12

Clinical guidelines recommend adjuvant chemotherapy for high-risk patients with Stage II-III colorectal cancer. However, chemotherapeutic administration rates differ significantly between hospitals. We assessed the prognostic benefit of adjuvant chemotherapy in patients with Stage IIb/c colorectal cancer, and the prognostic impact of interhospital variations in the administration of adjuvant chemotherapy for Stage II-III colorectal cancer. We conducted a multicentre, retrospective study of 17 757 patients with Stage II-III colorectal cancer treated between 1997 and 2008 in 23 hospitals in Japan. Hospitals were classified as high-rate (rate > 42.8%) or low-rate (rate ≤ 42.8%), chemotherapy prescribing clinics. The 5-year overall survival (OS) of patients with Stage II-III colorectal cancer receiving adjuvant chemotherapy was significantly higher than for those not receiving adjuvant chemotherapy (85.7% vs 79.2%, P colorectal cancer (both P colorectal cancer who received adjuvant chemotherapy, with patients who were treated in hospitals with high adjuvant chemotherapy rates demonstrating better prognoses. Colorectal Disease © 2018 The Association of Coloproctology of Great Britain and Ireland.

Coordinated research project on radiation sterilization and decontamination of pharmaceuticals and pharmaceutical raw materials. CRP report

International Nuclear Information System (INIS)

2005-01-01

Radiation processing is a very convenient tool for imparting desirable effects in materials and it has been an area of enormous interest in the last few decades. Radiation processing of synthetic and natural polymers for improving their characteristics is largely used in laboratory and industrial scale. Radiation sterilization is a well developed and established technology for many products. It is especially useful for the treatment of pharmaceuticals due to flexibility of radiation processing to be carried out at any desired temperature, sterilizability of mixed products in kits, offering simultaneous sterilization and modification of polymer based formulations. The success of radiation technology for processing of synthetic and natural polymers and treatment of pharmaceuticals has been based, to a large extent, on empirical knowledge. But now, the applications of natural polymers are being sought in knowledge-demanding areas such as pharmacy and biotechnology. Reliable analytical methods are being developed for controlling of degradation effects of radiation on polymers. Procedures and chemical formulations are being investigated enhancing or preventing degradation effects depending on the desired application of the process. The Coordinated Research Project (CRP) on the use of radiation processing for sterilization or decontamination of pharmaceuticals and pharmaceutical raw materials has been completed in 2002. The overall objective of the CRP was to coordinate the research and development programmes carried out in different countries in use of radiation processing for sterilization or decontamination of pharmaceuticals and pharmaceutic raw materials. It has been concluded that in addition to well known advantages of radiation sterilization being a well developed and established technology requiring the control of only one parameter, dose, to achieve sterilization; it is especially useful for the treatment of pharmaceuticals due to flexibility of radiation

Coordinated research project on radiation sterilization and decontamination of pharmaceuticals and pharmaceutical raw materials. CRP report

Energy Technology Data Exchange (ETDEWEB)

NONE

2005-07-01

Radiation processing is a very convenient tool for imparting desirable effects in materials and it has been an area of enormous interest in the last few decades. Radiation processing of synthetic and natural polymers for improving their characteristics is largely used in laboratory and industrial scale. Radiation sterilization is a well developed and established technology for many products. It is especially useful for the treatment of pharmaceuticals due to flexibility of radiation processing to be carried out at any desired temperature, sterilizability of mixed products in kits, offering simultaneous sterilization and modification of polymer based formulations. The success of radiation technology for processing of synthetic and natural polymers and treatment of pharmaceuticals has been based, to a large extent, on empirical knowledge. But now, the applications of natural polymers are being sought in knowledge-demanding areas such as pharmacy and biotechnology. Reliable analytical methods are being developed for controlling of degradation effects of radiation on polymers. Procedures and chemical formulations are being investigated enhancing or preventing degradation effects depending on the desired application of the process. The Coordinated Research Project (CRP) on the use of radiation processing for sterilization or decontamination of pharmaceuticals and pharmaceutical raw materials has been completed in 2002. The overall objective of the CRP was to coordinate the research and development programmes carried out in different countries in use of radiation processing for sterilization or decontamination of pharmaceuticals and pharmaceutic raw materials. It has been concluded that in addition to well known advantages of radiation sterilization being a well developed and established technology requiring the control of only one parameter, dose, to achieve sterilization; it is especially useful for the treatment of pharmaceuticals due to flexibility of radiation

Long-term outcomes of adjuvant radiotherapy after surgical resection of central neurocytoma

International Nuclear Information System (INIS)

Chen, Yi-Dong; Li, Wen-Bin; Feng, Jin; Qiu, Xiao-Guang

2014-01-01

The role of adjuvant radiotherapy for central neurocytomas (CNs) is not clear. Therefore, we aimed to examine the clinical outcomes of treating histologically confirmed CNs with adjuvant RT after surgical resection. Sixty-three CN patients were retrospectively evaluated: 24 patients underwent gross total resection (GTR); 28, subtotal resection (STR); 9, partial resection (PR), and 2, biopsy (Bx). They underwent adjuvant RT after surgery (median dose, 54 Gy). The median follow-up was 69 months (15–129 months). The 5-year overall survival (OS) and 5-year progression-free survival (PFS) were 94.4% and 95% after GTR + RT, 96.4% and 100% after STR + RT, and 100% and 90.9% after PR + RT. Only three patients had tumor recurrence: at the primary site at 30 and 24 months in two GTR + PR patients, and dissemination to the spinal cord at 75 months in one STR + RT patient. Thirty-eight (63.3%) patients experienced late neurotoxicity (28, grade 1; 7, grade 2; 3, grade 3). Short-term memory impairment was the most common toxicity. RT after incomplete resection (IR) led to OS and PFS comparable to those for GTR. Considering the excellent outcomes and limited late toxicity, adjuvant RT maybe a good option for CN patients who undergo IR

Estimating the adjuvant chemotherapy effect in elderly stage II and III colon cancer patients in an observational study.

Science.gov (United States)

Kim, Ki-Yeol; Cha, In-Ho; Ahn, Joong Bae; Kim, Nam Kyu; Rha, Sun Young; Chung, Hyun Cheol; Roh, Jae Kyung; Shin, Sang Joon

2013-05-01

Adjuvant chemotherapy has been known as a standard treatment for patients with resected colon cancer. However, in elderly colon cancer patients, the characteristics of patients are heterogeneous with regard to life expectancy and comorbidities. Thus, with regard to the effectiveness of adjuvant chemotherapy for colon cancer, it is difficult to extrapolate data of clinical trials from the younger into the older general population. Data for 382 elderly colon cancer patients were analyzed: 217 in Stage II and 165 in Stage III. The efficacy of adjuvant chemotherapy was evaluated in elderly colon cancer patients after a match by the propensity score method. For matched patients with Stage II colon cancer, there was no significant efficacy of adjuvant chemotherapy in the risk of death during all follow-up periods (P-value, 0.06-0.37). Though there was a tendency that the adjuvant chemotherapy reduces the death rate during the follow-up periods, it was not statistically significant. In the case of Stage III, the adjuvant chemotherapy was significantly effective in matched patients for 5-year (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.30-0.90) and overall survival (HR, 0.56; 95% CI, 0.34-0.94). Adjuvant chemotherapy for elderly patients with Stage II colon cancer is not effective, whereas elderly patients with Stage III with adjuvant chemotherapy appear to have a better survival rate in the general population. Copyright © 2012 Wiley Periodicals, Inc.

Radioimmunoassay of adjuvant-associated porcine parvovirus using a monoclonal antibody in a nitrocellulose membrane system

International Nuclear Information System (INIS)

Katz, J.B.; Van Deusen, R.A.

1985-01-01

A quantitative and simple indirect radioimmunoassay (IRIA) was developed for porcine parvovirus (PPV), employing a monoclonal antibody directed against PPV adsorbed to nitrocellulose membrane. The IRIA was equally sensitive to live or inactivated PPV. There was a linear relationship between membrane-bound radioactivity and PPV quantity within a range of 10-80 hemagglutinating (HA) units of virus. Two commercially used adjuvants, aluminum hydroxide (AH) and carboxyvinyl polymer (CP), reduced bound radioactivity in a concentration-dependent manner. At fixed adjuvant concentrations, there were, nevertheless, linear relationships between bound radioactivity and HA units of PPV. Known amounts of PPV were prepared in adjuvants according to commercial vaccine formulations. Using these standards, the PPV content of 16 commercial PPV vaccines was estimated by IRIA. The IRIA may be one practical method of in vitro estimation of antigenic mass in adjuvanted vaccines. (Auth.)

Adjuvant radiotherapy following radical hysterectomy for patients with stage IB and IIA cervical cancer

Energy Technology Data Exchange (ETDEWEB)

Soisson, A.P.; Soper, J.T.; Clarke-Pearson, D.L.; Berchuck, A.; Montana, G.; Creasman, W.T. (Duke Univ. Medical Center, Durham, NC (USA))

1990-06-01

From 1971 through 1984, 320 women underwent radical hysterectomy as primary therapy of stage IB and IIA cervical cancer. Two hundred forty-eight patients (78%) were treated with surgery alone and 72 patients (22%) received adjuvant postoperative external-beam radiotherapy. Presence of lymph node metastasis, large lesion (greater than 4 cm in diameter), histologic grade, race (noncaucasian), and age (greater than 40 years) were significant poor prognostic factors for the entire group of patients. Patients treated with surgery alone had a better disease-free survival than those who received combination therapy (P less than 0.001). However, patients receiving adjuvant radiation therapy had a higher incidence of lymphatic metastases, tumor involvement of the surgical margin, and large cervical lesions. Adjuvant pelvic radiation therapy did not improve the survival of patients with unilateral nodal metastases or those who had a large cervical lesion with free surgical margins and the absence of nodal involvement. Radiation therapy appears to reduce the incidence of pelvic recurrences. Unfortunately, 84% of patients who developed recurrent tumor after combination therapy had a component of distant failure. The incidence of severe gastrointestinal or genitourinary tract complications was not different in the two treatment groups. However, the incidence of lymphedema was increased in patients who received adjuvant radiation therapy. Although adjuvant radiation therapy appears to be tolerated without a significant increase in serious complications, the extent to which it may improve local control rates and survival in high-risk patients appears to be limited. In view of the high incidence of distant metastases in high-risk patients, consideration should be given to adjuvant systemic chemotherapy in addition to radiation therapy.

Cardiac safety of trastuzumab as adjuvant treatment for Japanese patients with early breast cancer

International Nuclear Information System (INIS)

Ishihara, Mikiya; Mukai, Hirofumi; Nagai, Shunji; Mukohara, Toru

2009-01-01

Recently, randomized trials revealed that trastuzumab as adjuvant treatment was effective in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients. Safety information on adjuvant trastuzumab use in Japanese patients, especially cardiac toxicity data, is needed. We retrospectively reviewed 48 patients with early-stage HER2-positive breast cancer who were treated with curative surgery and adjuvant trastuzumab at the National Cancer Center Hospital East (Kashiwa, Japan). The cardiac safety as well as the short-term efficacy of trastuzumab were evaluated. The median age of the patients was 54 years. All patients received adjuvant or neoadjuvant cytotoxic chemotherapy. Twenty-seven patients (56%) received adjuvant radiation therapy. Forty-four patients (92%) received trastuzumab without concurrent cytotoxic chemotherapy and 4 patients (8%) on taxanes received trastuzumab concurrently. Twenty-five patients completed 1 year of trastuzumab treatment and 5 patients completed 2 years of trastuzumab treatment. Nine patients discontinued trastuzumab treatment, because of progressive disease (1 patient), decrease in left ventricular ejection fraction (LVEF; 2 patients), patient's refusal (4 patients), and other reasons (2 patients). There were five cardiac events. A decrease in LVEF to less than 50% was seen in 2 patients. The relationship between trastuzumab treatment and the cardiac events was unclear in 3 patients. The median follow-up time was 21.2 months. The disease-free survival (DFS) was 97.5% at 1 year and 92.9% at 2 years. The incidence of cardiac events caused by trastuzumab treatment was low in our analysis. Adjuvant trastuzumab treatment for up to at least 1 year should be safe for Japanese breast cancer patients. (author)

FORMATION AND FURTHER DEVELOPMENT OF MODERN PROMOTION OF PHARMACEUTICAL PRODUCTS

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Юрий Владимирович Тарасов

2014-02-01

Full Text Available The articles addresses key notions and elements of marketing of pharmaceutical companies. Key stages and particularities of formation of pharmaceutical marketing are considered. It is proved that in general pharmaceutical market is developing under general marketing rules, however while developing strategy of promotion of pharmaceutical products specific features of the industry must be taken into consideration. The authors describes specific features of modern pharmaceutical market, which must be considered while developing policy of promotion of pharmaceutical products.The analysis is made of modern state of Russian pharmaceutical industry, its place in world pharmaceutical market. It is found that development of pharmaceutical market is directly influenced by the reform of pharmaceutical industry initiated by the Government of our country in 2008. Characteristic of current stage of market development is more strict conditions in marketing sphere and promotion of drugs. DOI: http://dx.doi.org/10.12731/2218-7405-2013-12-2

Application of radio-detoxified endotoxin as adjuvant for experimental foot-and-mouth disease vaccine

Energy Technology Data Exchange (ETDEWEB)

Solyom, F; Bertok, L

1985-01-01

The immunity enhancing adjuvant activity of radiodetoxified endotoxin (RD-LPS) on the potency of C type foot-and-mouth (FMD) vaccine was tested in different animal species. For radiodetoxification 5 Mrad gamma radiation was used. The suitable quantity of RD-LSP (20 ..mu..g per mouse) adjuvated FMD vaccines of lower antigen content better than those of higher one. In cattle and sheep the adjuvant effect of oil + RD + LPS surpassed only slightly that of oil alone. The effect of RD-LPS in pig was very pronounced when applied in small doses but further studies in larger animal populations have to confirm this result. (author). 14 references, 6 tables.

Effectiveness of Brucella abortus lipopolysaccharide as an adjuvant for tuberculin PPD.

Science.gov (United States)

Jamalan, Mostafa; Ardestani, Susan Kaboudanian; Zeinali, Majid; Mosaveri, Nader; Mohammad Taheri, Mohammad

2011-01-01

Bacterial lipopolysaccharide (LPS) has T-helper 1 (Th1) immunostimulatory activities but because of toxicity and pyrogenicity cannot be used as an adjuvant. Brucella abortus LPS has less toxicity and no pyrogenic properties in comparison to other bacterial LPS. In the current study, the immunostimulatory properties of B. abortus LPS were evaluated for its adjuvant activity. Tuberculin purified protein derivative (PPD) from Mycobacterium tuberculosis was extracted and after anion-exchange chromatography on Q-sepharose column, two fractions (17 and 23), which dominantly contained 30- and 70-kDa antigens, were collected for immunological studies. BALB/c mice were immunized with four different antigen preparations (BCG, PPD, 17th and 23rd PPD fractions) along with complete Freund's adjuvant or B. abortus LPS. The T-cell immune response of mice was assessed by measurement of Th1-type cytokine (IFN-γ) and Th2-type cytokines (IL-5 and IL-10) levels. Also, the humoral immunity was evaluated by measuring the specific IgG levels. Our results showed that immunization of mice with 17th PPD fraction along with B. abortus LPS can induce a Th1-type cytokine response characterized with a high IFN-γ/IL-5 ratio, while immunization with PPD or 23rd PPD fraction along with the same adjuvant resulted to a mixed Th1/Th2-type cytokine response. Copyright © 2010 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.

Tailorable Trimethyl chitosans as adjuvant for intranasal immunization

NARCIS (Netherlands)

Verheul, R.J.

2010-01-01

Tailorable Trimethyl Chitosans as Adjuvant for Intranasal Immunization Active vaccination has proven to be the most (cost) effective tool in the fight against infectious diseases. Nowadays, most vaccines are administered via parenteral injection. However, the risk of contaminated needles and need

Pharmaceutical care education in Kuwait: pharmacy students’ perspectives

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Katoue MG

2014-09-01

Full Text Available Background: Pharmaceutical care is defined as the responsible provision of medication therapy to achieve definite outcomes that improve patients’ quality of life. Pharmacy education should equip students with the knowledge, skills, and attitudes they need to practise pharmaceutical care competently. Objective: To investigate pharmacy students’ attitudes towards pharmaceutical care, perceptions of their preparedness to perform pharmaceutical care competencies, opinions about the importance of the various pharmaceutical care activities, and the barriers to its implementation in Kuwait. Methods: A descriptive, cross-sectional survey of pharmacy students (n=126 was conducted at Faculty of Pharmacy, Kuwait University. Data were collected via a pre-tested self-administered questionnaire. Descriptive statistics including percentages, medians and means Likert scale rating (SD were calculated and compared using SPSS, version 19. Statistical significance was accepted at a p value of 0.05 or lower. Results: The response rate was 99.2%. Pharmacy students expressed overall positive attitudes towards pharmaceutical care. They felt prepared to implement the various aspects of pharmaceutical care, with the least preparedness in the administrative/management aspects. Perceived pharmaceutical care competencies grew as students progressed through the curriculum. The students also appreciated the importance of the various pharmaceutical care competencies. They agreed/strongly agreed that the major barriers to the integration of pharmaceutical care into practice were lack of private counseling areas or inappropriate pharmacy layout (95.2%, lack of pharmacist time (83.3%, organizational obstacles (82.6%, and pharmacists’ physical separation from patient care areas (82.6%. Conclusion: Pharmacy students’ attitudes and perceived preparedness can serve as needs assessment tools to guide curricular change and improvement. Student pharmacists at Kuwait University

Supply Chain Management in Zhendong Pharmaceutical Company

OpenAIRE

Li, Yan

2011-01-01

Medicines are special commodity related to people’s lives and health, therefore, pharmaceutical distribution is an industry affecting the national economy and the people's livelihood. With health care reform, changeable pharmaceutical policy and fiercely increasing competition in the medical industry, pharmaceutical distribution companies should improve their level of logistics operations and reduce overall logistics management costs in order to gain a leading position in the competition. In ...

Enhancement of the Immunogenicity and Protective Efficacy of a Mucosal Influenza Subunit Vaccine by the Saponin Adjuvant GPI-0100

NARCIS (Netherlands)

Liu, Heng; Patil, Harshad P.; de Vries-Idema, Jacqueline; Wilschut, Jan; Huckriede, Anke

2012-01-01

Identification of safe and effective adjuvants remains an urgent need for the development of inactivated influenza vaccines for mucosal administration. Here, we used a murine challenge model to evaluate the adjuvant activity of GPI-0100, a saponin-derived adjuvant, on influenza subunit vaccine

[Fourcroy and pharmaceutical journals].

Science.gov (United States)

Bonnemain, Bruno

2011-04-01

Cadet de Gassicourt wrote a brief Eloge of Fourcroy in January 1810 as he died in December of 1809. Fourcroy had a major role concerning the new ideas on the place of pharmacy at the beginning of the 19th century. Fourcroy has had a key influence for the start of several pharmaceutical journals that wanted to emphasize the link between the new chemistry and pharmacy. None of these journals created with him will survive and one has to wait for 1909 to see the creation, without Fourcroy, of a new pharmaceutical journal, the "Journal de Pharmacie" that will become "Journal de Pharmacie et des Sciences accessoires", then "Journal de Pharmacie et de Chimie", before taking the name of"Annales Pharmaceutiques Françaises", the present official journal of the French Academy of Pharmacy. In spite of the essential role of Fourcroy at the start of pharmaceutical journals, Cadet did not even mention it in his Eloge of 1810.

Vaccine Adjuvants in Fish Vaccines Make a Difference: Comparing Three Adjuvants (Montanide ISA763A Oil, CpG/Poly I:C Combo and VHSV Glycoprotein Alone or in Combination Formulated with an Inactivated Whole Salmonid Alphavirus Antigen

Directory of Open Access Journals (Sweden)

Hanna L. Thim

2014-03-01

Full Text Available Most commercial vaccines offered to the aquaculture industry include inactivated antigens (Ag formulated in oil adjuvants. Safety concerns are related to the use of oil adjuvants in multivalent vaccines for fish, since adverse side effects (e.g., adhesions can appear. Therefore, there is a request for vaccine formulations for which protection will be maintained or improved, while the risk of side effects is reduced. Here, by using an inactivated salmonid alphavirus (SAV as the test Ag, the combined use of two Toll-like receptor (TLR ligand adjuvants, CpG oligonucleotides (ODNs and poly I:C, as well as a genetic adjuvant consisting of a DNA plasmid vector expressing the viral haemorrhagic septicaemia virus (VHSV glycoprotein (G was explored. VHSV-G DNA vaccine was intramuscularly injected in combination with intraperitoneal injection of either SAV Ag alone or combined with the oil adjuvant, Montanide ISA763, or the CpG/polyI:C combo. Adjuvant formulations were evaluated for their ability to boost immune responses and induce protection against SAV in Atlantic salmon, following cohabitation challenge. It was observed that CpG/polyI:C-based formulations generated the highest neutralizing antibody titres (nAbs before challenge, which endured post challenge. nAb responses for VHSV G-DNA- and oil-adjuvanted formulations were marginal compared to the CpG/poly I:C treatment. Interestingly, heat-inactivated sera showed reduced nAb titres compared to their non-heated counterparts, which suggests a role of complement-mediated neutralization against SAV. Consistently elevated levels of innate antiviral immune genes in the CpG/polyI:C injected groups suggested a role of IFN-mediated responses. Co-delivery of the VHSV-G DNA construct with either CpG/polyI:C or oil-adjuvanted SAV vaccine generated higher CD4 responses in head kidney at 48 h compared to injection of this vector or SAV Ag alone. The results demonstrate that a combination of pattern recognizing

Prospective and comparative assessment of toxicity of adjuvant concomitant chemo-radiotherapy after neo-adjuvant chemotherapy in breast cancer; evaluation prospective et comparative de la toxicite de la chimioradiotherapie concomitante adjuvante apres chimiotherapie neoadjuvante dans le cancer du sein

Energy Technology Data Exchange (ETDEWEB)

Marchand, V.; Angelergues, A.; Gobaux, V.; Kirova, Y.M.; Campana, F.; Dendale, R.; Reyal, F.; Pierga, J.Y.; Fourquet, A.; Bollet, M.A. [Institut Curie, Paris (France)

2011-10-15

The authors report a prospective assessment of toxicity a treatment comprising an adjuvant chemo-radiotherapy after neo-adjuvant chemotherapy and a comparison with a treatment comprising only radiotherapy. Two sets of patients have been treated for a breast cancer between 1997 and 2002 by association of neo-adjuvant chemotherapy, surgery and radiotherapy with or without concomitant chemotherapy. Late toxicity has been assessed prospectively according to Common Terminology Criteria for Adverse Events. Acute toxicity has been noticed in medical files. The analysis of 142 treatments reveals that the concomitant administration of chemotherapy to radiotherapy after neo-adjuvant chemotherapy and surgery is associated with an increase of acute toxicity without increase of long term toxicity. Short communication

Analysis of the dose-sparing effect of adjuvanted Sabin-inactivated poliovirus vaccine (sIPV).

Science.gov (United States)

Li, Zhuofan; Ding, Wenting; Guo, Qi; Liu, Ze; Zhu, Zhe; Song, Shaohui; Li, Weidong; Liao, Guoyang

2018-03-30

Sabin-based inactivated poliovirus vaccine(sIPV) is gradually replacing live-attenuated oral polio vaccine(OPV). Sabin-inactivated poliovirus vaccine(sIPV) has played a vital role in reducing economic burden of poliomyelitis and maintaining appropriate antibody levels in the population. However, due to its high cost and limited manufacturing capacity, sIPV cannot reach its full potential for global poliovirus eradication in developing countries. Therefore, to address this situation, we designed this study to evaluate the dose-sparing effects of AS03, CpG oligodeoxynucleotides (CpG-ODN) and polyinosinic:polycytidylic acid (PolyI:C) admixed with sIPV in rats. Our results showed that a combination of 1/4-dose sIPV adjuvanted with AS03 or AS03 with BW006 provides a seroconversion rate similar to that of full-dose sIPV without adjuvant and that, this rate is 5-fold higher than that of 1/4-dose sIPV without adjuvant after the first immunization. The combination of AS03 or AS03 with BW006 as an adjuvant effectively reduced sIPV dose by at least 4-fold and induced both humoral and cellular immune responses. Therefore, our study revealed that the combination of AS03 or AS03 with BW006 is a promising adjuvant for sIPV development.

NMR imaging and pharmaceutical sciences

International Nuclear Information System (INIS)

Beall, P.T.; Good, W.R.

1986-01-01

Described is the technique of NMR-imaging in diagnostic medicine. Proton and phosphorus NMR in diagnosis of abnormal tissue pathology. Discussed is the value of NMR to the pharmaceutical sciences. NMR may play an important role in monitoring the response of tissues to drugs, determining the localization of drugs, performing real time pharmacokinetics and testing the use of NMR contrast pharmaceuticals

Bioremediation Kinetics of Pharmaceutical Industrial Effluent

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M. Šabić

2015-05-01

Full Text Available In recent years, concerns about the occurrence and fate of pharmaceuticals that could be present in water and wastewater has gained increasing attention. With the public’s enhanced awareness of eco-safety, environmentally benign methods based on microorganisms have become more accepted methods of removing pollutants from aquatic systems. This study investigates bioremediation of pharmaceutical wastewater from pharmaceutical company Pliva Hrvatska d.o.o., using activated sludge and bioaugmented activated sludge with isolated mixed bacterial culture. The experiments were conducted in a batch reactor in submerged conditions, at initial concentration of organic matter in pharmaceutical wastewater, expressed as COD, 5.01 g dm–3 and different initial concentrations of activated sludge, which ranged from 1.16 to 3.54 g dm–3. During the experiments, the COD, pH, concentrations of dissolved oxygen and biomass were monitored. Microscopic analyses were performed to monitor the quality of activated sludge. Before starting with the bioremediation in the batch reactor, toxicity of the pharmaceutical wastewater was determined by toxicity test using bacteria Vibrio fischeri. The obtained results showed that the effective concentration of the pharmaceutical wastewater was EC50 = 17 % and toxicity impact index was TII50 = 5.9, meaning that the untreated pharmaceutical industrial effluent must not be discharged into the environment before treatment. The results of the pharmaceutical wastewater bioremediation process in the batch reactor are presented in Table 1. The ratio γXv ⁄ γX maintained high values throughout all experiments and ranged from 0.90 and 0.95, suggesting that the concentrations of biomass remained unchanged during the experiments. The important kinetic parameters required for performance of the biological removal process, namely μmax, Ks, Ki, Y and kd were calculated from batch experiments (Table 2. Figs. 1 and 2 show the experimental

Diagnostic and therapeutic approaches in Italian hospitals: adjuvant and metastatic therapy in melanoma.

Science.gov (United States)

Chiarion-Sileni, Vanna; Guida, Michele; Romanini, Antonella; Bernengo, Maria Grazia; Ascierto, Paolo; Queirolo, Paola; Mandalà, Mario; Maio, Michele; Ferraresi, Virginia; Stanganelli, Ignazio; Testori, Alessandro; Ridolfi, Ruggero

2013-01-01

Melanoma incidence and mortality rates are rising in Italy, indicating that more effective treatments are required both in the adjuvant and metastatic settings. We analyzed clinical practices in the adjuvant and metastatic settings by conducting a nationwide survey of clinicians responsible for managing melanoma treatment and follow-up in a representative sample of Italian hospitals. 95% of participating hospitals completed the panel of questions on adjuvant and metastatic treatment, making it likely that these results give a realistic picture of treatment and follow-up of melanoma patients in Italy. In low-volume hospitals (<25 new melanoma diagnoses yearly) adjuvant therapy was significantly more used than in large-volume hospitals for patients in stage III and IV (82 versus 66% and 56 versus 30%, respectively), and only 11% of patients were enrolled in clinical trials. In the metastatic setting dacarbazine was the preferred first-line treatment (32%) followed by polychemotherapy (23%); 12% of patients were enrolled in clinical trials and less than 10% received interleukin-2, usually subcutaneously. The information provided by this study was used by the Italian Melanoma Intergroup to improve the quality of care and to redirect financial resources. Copyright © 2013 S. Karger AG, Basel.

Computational prediction of multidisciplinary team decision-making for adjuvant breast cancer drug therapies: a machine learning approach.

Science.gov (United States)

Lin, Frank P Y; Pokorny, Adrian; Teng, Christina; Dear, Rachel; Epstein, Richard J

2016-12-01

Multidisciplinary team (MDT) meetings are used to optimise expert decision-making about treatment options, but such expertise is not digitally transferable between centres. To help standardise medical decision-making, we developed a machine learning model designed to predict MDT decisions about adjuvant breast cancer treatments. We analysed MDT decisions regarding adjuvant systemic therapy for 1065 breast cancer cases over eight years. Machine learning classifiers with and without bootstrap aggregation were correlated with MDT decisions (recommended, not recommended, or discussable) regarding adjuvant cytotoxic, endocrine and biologic/targeted therapies, then tested for predictability using stratified ten-fold cross-validations. The predictions so derived were duly compared with those based on published (ESMO and NCCN) cancer guidelines. Machine learning more accurately predicted adjuvant chemotherapy MDT decisions than did simple application of guidelines. No differences were found between MDT- vs. ESMO/NCCN- based decisions to prescribe either adjuvant endocrine (97%, p = 0.44/0.74) or biologic/targeted therapies (98%, p = 0.82/0.59). In contrast, significant discrepancies were evident between MDT- and guideline-based decisions to prescribe chemotherapy (87%, p machine learning models. A machine learning approach based on clinicopathologic characteristics can predict MDT decisions about adjuvant breast cancer drug therapies. The discrepancy between MDT- and guideline-based decisions regarding adjuvant chemotherapy implies that certain non-clincopathologic criteria, such as patient preference and resource availability, are factored into clinical decision-making by local experts but not captured by guidelines.

Nurse practitioners' perceptions and participation in pharmaceutical marketing.

Science.gov (United States)

Crigger, Nancy; Barnes, Kristen; Junko, Autumn; Rahal, Sarah; Sheek, Casey

2009-03-01

This paper reports on a study conducted to describe family nurse practitioners' perceptions towards and participation in pharmaceutical marketing and to explore the relationships among related variables. The pharmaceutical industry's intense global marketing strategies have resulted in widespread concern in healthcare professionals and professional groups, sectors of the public in many countries, and in the World Health Organization. Research on healthcare providers' participation in pharmaceutical marketing indicates that these relationships are conflicts of interests and compromise healthcare providers' prescribing practices and trust. Nursing, as a discipline, appears to be slow to address the impact of pharmaceutical marketing on nursing practice. Questionnaires about perceptions and participation in pharmaceutical marketing were completed by a random sample of 84 licensed family nurse practitioners in the United States of America in 2007. Family nurse practitioners viewed pharmaceutical company marketing uncritically as educational and beneficial. They also perceived other providers but not themselves as influenced by pharmaceutical marketing. The findings supported those found in previous research with nurses and physicians. Lack of education, participation in marketing and psychological and social responses may impede family nurse practitioners' ability to respond critically and appropriately to marketing strategies and the conflict of interest it creates.

Retrospective analysis on prognostic impact of adjuvant chemotherapy in the patients with advanced and resectable oral squamous cell carcinoma

International Nuclear Information System (INIS)

Kurita, Hiroshi; Koike, Takeshi; Miyazawa, Hideki; Uehara, Shinobu; Kobayashi, Hiroichi; Kurashina, Kenji

2006-01-01

The effect of adjuvant chemotherapy on oral squamous cell carcinoma (SCC) is unclear mainly because there have been a few studies which evaluate the efficacy of adjuvant chemotherapy. The purpose of this retrospective study was to analyze the efficacy of adjuvant chemotherapy in the patients with advanced and resectable oral SCC. Forty-one patients in whom advanced SCC (stage III and IV) was completely removed were included in this study. The impact of multiple variables including T-classification, degree of differentiation, mode of invasion, number and level of cervical metastatic node, pre- and post-operative radiation therapy, neoadjuvant chemotherapy, and adjuvant chemotherapy on survival and control of local relapse or distant metastasis was assessed using the stepwise Cox proportional hazards model. The level of neck node metastasis (p<0.02) was a significant independent predictor for cause-specific survival and adjuvant chemotherapy was of borderline significance (p=0.07). The number of neck node metastasis (p<0.01) and adjuvant chemotherapy (p<0.01) were significantly related with disease free survival. The results of this retrospective study suggested that adjuvant chemotherapy had a significant benefit in improving disease free survival. (author)

Prognostic factors for patients with early-stage uterine serous carcinoma without adjuvant therapy.

Science.gov (United States)

Tate, Keisei; Yoshida, Hiroshi; Ishikawa, Mitsuya; Uehara, Takashi; Ikeda, Shun Ichi; Hiraoka, Nobuyoshi; Kato, Tomoyasu

2018-05-01

Uterine serous carcinoma (USC) is an aggressive type 2 endometrial cancer. Data on prognostic factors for patients with early-stage USC without adjuvant therapy are limited. This study aims to assess the baseline recurrence risk of early-stage USC patients without adjuvant treatment and to identify prognostic factors and patients who need adjuvant therapy. Sixty-eight patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II USC between 1997 and 2016 were included. All the cases did not undergo adjuvant treatment as institutional practice. Clinicopathological features, recurrence patterns, and survival outcomes were analyzed to determine prognostic factors. FIGO stages IA, IB, and II were observed in 42, 7, and 19 cases, respectively. Median follow-up time was 60 months. Five-year disease-free survival (DFS) and overall survival (OS) rates for all cases were 73.9% and 78.0%, respectively. On multivariate analysis, cervical stromal involvement and positive pelvic cytology were significant predictors of DFS and OS, and ≥1/2 myometrial invasion was also a significant predictor of OS. Of 68 patients, 38 patients had no cervical stromal invasion or positive pelvic cytology and showed 88.8% 5-year DFS and 93.6% 5-year OS. Cervical stromal invasion and positive pelvic cytology are prognostic factors for stage I-II USC. Patients with stage IA or IB USC showing negative pelvic cytology may have an extremely favorable prognosis and need not receive any adjuvant therapies. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

The mechanism of action of MF59 - an innately attractive adjuvant formulation.

Science.gov (United States)

O'Hagan, D T; Ott, G S; De Gregorio, E; Seubert, A

2012-06-19

MF59 is a safe and effective vaccine adjuvant which was originally approved to be included in a licensed influenza vaccine to be used in the elderly in Europe in 1997. The MF59 adjuvanted influenza vaccine (Fluad™) is now licensed in more than 20 countries worldwide and more than 85 million doses have been administered. More recently the vaccine adjuvant has also been shown to be safe and effective in young children and resulted in a significant increase in influenza vaccine efficacy in a controlled clinical trial in Europe. Since the early days of its discovery we have explored the mechanism of action of MF59, using a variety of available techniques. In recent years we have explored more thoroughly the mechanism of action using new and more sophisticated techniques. It is remarkable how consistent the data has been, using a variety of different approaches both in several small animal models and also using human immune cells in vitro. Here we present a summary of all the work performed to date on the mechanism of action of MF59 and we present a unified theory based on the accumulated data of how it exerts its adjuvant effects. A key element of the mechanism of action appears to be the creation of a transient 'immunocompetent' local environment at the injection site, resulting in the recruitment of key immune cells, which are able to take up antigen and adjuvant and transport them to the local lymph nodes, where the immune response is induced. This recruitment appears to be triggered by the induction of a chemokine driven gradient by the impact of MF59 on local cells, which are activated to secrete further chemokines, which are recruitment factors for more immune cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

Pharmaceutical drug detailing in primary care: extent and methods

DEFF Research Database (Denmark)

Schramm, Jesper

The dimension and methods of pharmaceutical marketing towards 47 danish general practitioners is described. Conclusions: Pharmaceutical drug detailing possesses a huge potential to influence the prescription pattern of GP's.......The dimension and methods of pharmaceutical marketing towards 47 danish general practitioners is described. Conclusions: Pharmaceutical drug detailing possesses a huge potential to influence the prescription pattern of GP's....

EU pharmaceutical expenditure forecast.

Science.gov (United States)

Urbinati, Duccio; Rémuzat, Cécile; Kornfeld, Åsa; Vataire, Anne-Lise; Cetinsoy, Laurent; Aballéa, Samuel; Mzoughi, Olfa; Toumi, Mondher

2014-01-01

With constant incentives for healthcare payers to contain their pharmaceutical budgets, forecasting has become critically important. Some countries have, for instance, developed pharmaceutical horizon scanning units. The objective of this project was to build a model to assess the net effect of the entrance of new patented medicinal products versus medicinal products going off-patent, with a defined forecast horizon, on selected European Union (EU) Member States' pharmaceutical budgets. This model took into account population ageing, as well as current and future country-specific pricing, reimbursement, and market access policies (the project was performed for the European Commission; see http://ec.europa.eu/health/healthcare/key_documents/index_en.htm). In order to have a representative heterogeneity of EU Member States, the following countries were selected for the analysis: France, Germany, Greece, Hungary, Poland, Portugal, and the United Kingdom. A forecasting period of 5 years (2012-2016) was chosen to assess the net pharmaceutical budget impact. A model for generics and biosimilars was developed for each country. The model estimated a separate and combined effect of the direct and indirect impacts of the patent cliff. A second model, estimating the sales development and the risk of development failure, was developed for new drugs. New drugs were reviewed individually to assess their clinical potential and translate it into commercial potential. The forecast was carried out according to three perspectives (healthcare public payer, society, and manufacturer), and several types of distribution chains (retail, hospital, and combined retail and hospital). Probabilistic and deterministic sensitivity analyses were carried out. According to the model, all countries experienced drug budget reductions except Poland (+€41 million). Savings were expected to be the highest in the United Kingdom (-€9,367 million), France (-€5,589 million), and, far behind them

Doctors and pharmaceutical industry.

Science.gov (United States)

Beran, Roy G

2009-09-01

The pharmaceutical industry is seen as seducing doctors by providing expensive gifts, subsidising travel and underwriting practice expenses in return for those doctors prescribing products that otherwise they would not use. This paints doctors in a very negative light; suggests doctors are available to the highest bidder; implies doctors do not adequately act as independent agents; and that doctors are driven more by self-interest than by patient needs. Similar practices, in other industries, are accepted as normal business behaviour but it is automatically assumed to be improper if the pharmaceutical industry supports doctors. Should the pharmaceutical industry withdraw educational grants then there would be: fewer scientific meetings; reduced attendance at conferences; limited post graduate education; and a depreciated level of maintenance of professional standards. To suggest that doctors prescribe inappropriately in return for largesse maligns their integrity but where there is no scientific reason to choose between different treatments then there can be little argument against selecting the product manufactured by a company that has invested in the doctor and the question arises as to whether this represents bad medicine? This paper will examine what constitutes non-professional conduct in response to inducements by the pharmaceutical industry. It will review: conflict of interest; relationships between doctors and pharma and the consequences for patients; and the need for critical appraisal before automatically decrying this relationship while accepting that there remain those who do not practice ethical medicine.

The Impact of Biotechnology on Pharmaceutics.

Science.gov (United States)

Block, Lawrence H.

1990-01-01

The emergence of bioactive peptides and proteins as new drug species poses formidable problems for the pharmaceutical scientist. Implications for revision or change in undergraduate and graduate pharmaceutics curricula derive from the biopharmaceutical, pharmacokinetic, and physiochemical aspects of the new drug species, which differ from…

Pharmaceutical counseling: Between evidence-based medicine and profits.

Science.gov (United States)

Egorova, S N; Akhmetova, T

2015-01-01

The number of pharmacies, which produce drug formulations locally, has recently considerably reduced in Russia. Pharmacies mainly operate as retailers of industrially manufactured drugs.Pharmaceutical consultation of customers at pharmacies aimed at responsible self-medication is the most popular and accessible feature of pharmaceutical care. In Russia there is a significant list of medicines approved for sale in pharmacies on a non-prescription basis that is specified in the product label. In this regard, the role of pharmacists in public health in Russia increases. Pharmacist, working directly with population, is an important figure for the rational use of medicines. This type of work requires high level of professional training and appropriate ethics. To explore the current status of pharmaceutical counseling in Russia. Situation analysis, surveys of pharmacists. Our experience in the system of postgraduate professional education, the results of the survey of pharmacists, and the long-term dialogue with pharmacists allowed us to identify several unresolved issues in the work of a pharmacist selling non-prescription drugs.Lack of differentiation in the functions of a pharmacist with a higher education and pharmaceutical technologist: In production/industrial pharmacy technicians are engaged in manufacturing of pharmaceutical formulations. However, due to the loss of production functions technologists had to move away from production laboratories of apothecaries to the sales area. Currently, the apothecary's assignment to receive prescriptions and dispense medications can be fulfilled by either a pharmacist or a pharmaceutical technician. It significantly discerns the pharmacy from the medical organization with clearly delineated functions of doctors and nurses. Russian regulations should consider the level of education required for high-quality pharmaceutical counseling.Contradiction between the pharmacist's special functions and trade procedure with the lack of

Tabletted guar gum microspheres of piroxicam for targeted adjuvant therapy for colonic adenocarcinomas.

Science.gov (United States)

Vats, Anima; Pathak, Kamla

2012-11-01

In recent years, nonsteroidal anti-inflammatory drugs have been found to be cogent as an adjuvant therapeutic agent in mitigating colorectal cancer. Thus, this present investigation was aimed to formulate an oral, targeted tablet of piroxicam microspheres for sustained and targeted adjuvant therapy for colonic adenocarcinomas. Crosslinked guar gum microspheres of piroxicam were directly compressed into matrix tablet and coated with Eudragit S100. The optimized tablet that displayed 0% release in simulated gastric fluid, 15% in simulated intestinal fluid and 97.1% in simulated colonic fluid underwent roentgenographic study in rabbits to check its safe transit to the colon. x-ray images revealed intactness of the tablet until it reached the colon where the tablet matrix eroded. The designed, conceptual formulation emerged as potential carrier for targeted adjuvant therapy of piroxicam.

PMA Induces Vaccine Adjuvant Activity by the Modulation of TLR Signaling Pathway

Directory of Open Access Journals (Sweden)

Dool-Ri Oh

2014-01-01

Full Text Available Toll-like receptor (TLR ligands are being developed for use as vaccine adjuvants and as immunomodulators because of their ability to stimulate innate and adaptive immune responses. Flagellin, a TLR5 ligand, was reported to show potent mucosal vaccine adjuvant activity. To identify ligands that potentiate the adjuvant activity of flagellin, we screened a plant library using HEK293T cells transiently cotransfected with phTLR5 and pNF-κB-SEAP plasmids. The 90% EtOH extract from Croton tiglium showed significant NF-κB transactivation in a TLR5-independent manner along with the increase of a flagellin activity. We have studied to characterize an active component from Croton tiglium and to elucidate the action mechanisms. Phorbol 12-myristate 13-acetate (PMA was isolated as an active component of Croton tiglium by activity-guided fractionation, column chromatography, HPLC, NMR, and MS. PMA at a range of nM induced PKC-dependent NF-κB activation and IL-8 production in both TLR5− and TLR5+ assay systems. In in vivo mouse vaccination model, PMA induced antigen-specific IgG and IgA antibody responses and increased IL-12 production corresponding to T cell responses in spleen lymphocytes. These results suggest that PMA would serve as an efficacious mucosal vaccine adjuvant.

[The aspects of pricing policy in Azerbaijan pharmaceutical sector].

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Dzhalilova, K I; Alieva, K Ia

2012-01-01

The effect of macro-, middle- and microeconomic factors on price formation in Azerbaijan pharmaceutical market has been studied. Worldwide pharmaceutical leaders have the goals to become leader on the pharmaceutical market of Azerbaijan and maximize their market share. Non-leaders pharmaceutical companies use different strategies of price formation: prime cost plus markup, or price formation on the base of current prices. It was revealed that domestic pharmaceutical market has high demand elasticity. Future market development is related to stimulation of product development, and hard penetration to the market through realization of price formation strategy. Non-state pharmaceutical organizations to achieve the purpose of survive in conditions of high competition should take in to account the factor perceptions of assortment by customers.

Uptake and depuration of pharmaceuticals in aquatic invertebrates

International Nuclear Information System (INIS)

Meredith-Williams, Melanie; Carter, Laura J.; Fussell, Richard; Raffaelli, David; Ashauer, Roman; Boxall, Alistair B.A.

2012-01-01

The uptake and depuration of a range of pharmaceuticals in the freshwater shrimp (Gammarus pulex) and the water boatman (Notonecta glauca) was studied. For one compound, studies were also done using the freshwater snail Planobarius corneus. In G. pulex, bioconcentration factors (BCFs) ranged from 4.6 to 185,900 and increased in the order moclobemide < 5-fluoruracil < carbamazepine < diazepam < carvedilol < fluoxetine. In N. glauca BCFs ranged from 0.1 to 1.6 and increased in the order 5-fluorouracil < carbamazepine < moclobemide < diazepam < fluoxetine < carvedilol. For P. corneus, the BCF for carvedilol was 57.3. The differences in degree of uptake across the three organisms may be due to differences in mode of respiration, behaviour and the pH of the test system. BCFs of the pharmaceuticals for each organism were correlated to the pH-corrected liposome–water partition coefficient of the pharmaceuticals. - Highlights: ► One of the first studies exploring the uptake of pharmaceuticals into aquatic invertebrates. ► Data presented on uptake, depuration rates and bioconcentration for a range of pharmaceuticals. ► Uptake is correlated with the pH-corrected liposome–water partition coefficient. ► Findings can be used to better predict impacts of pharmaceuticals on the aquatic environment. - The factors affecting the degree of uptake of pharmaceuticals into aquatic invertebrates were studied. The results indicate that species traits such as respiration and behaviour of the organisms and pH-corrected liposome–water partition coefficients are important factors in determining pharmaceutical uptake.

Pharmaceutical and Medicine Manufacturing Sector (NAICS 3254)

Science.gov (United States)

Find environmental regulatory and compliance information for the pharmaceutical manufacturing sector, including essential uses of CFCs, NESHAP for pharmaceutical production, effluent guidelines for wastewater and management of hazardous waste.

Adjuvant chemo- and radiotherapy in gastrointestinal tumors; Adjuvante Chemo- und Strahlentherapie bei gastrointestinalen Tumoren

Energy Technology Data Exchange (ETDEWEB)

Sendler, A. [Technische Univ. Muenchen (Germany). Chirurgische Klinik und Poliklinik; Feldmann, H.J. [Technische Univ. Muenchen (Germany). Inst. und Poliklinik fuer Strahlentherapie und Radiologische Onkologie; Fink, U. [Technische Univ. Muenchen (Germany). Chirurgische Klinik und Poliklinik; Molls, M. [Technische Univ. Muenchen (Germany). Inst. und Poliklinik fuer Strahlentherapie und Radiologische Onkologie; Siewert, J.R. [Technische Univ. Muenchen (Germany). Chirurgische Klinik und Poliklinik

1995-04-21

In modern surgical oncology, adjuvant therapies are important complementary strategies. In local advanced carcinomas of the gastrointestinal tract, 5-year survival data are still disappointing despite standardized surgery. In this context, it has to be differentiated between adjuvant therapy following complete tumor exstirpation (so-called UICC R{sub 0} resection) and additive therapies following incomplete tumor resections (UICC R{sub 1} or R{sub 2} resection). Modalities in the adjuvant setting are chemotherapy, radiotherapy or the combined radio-/chemotherapy. In esophageal and gastric cancer there is up to now no benefit of postoperative adjuvant therapy. In pancreatic cancer, there are studies indicating a benefit of combined radio-/chemotherapy after complete tumor resection. A standard adjuvant chemotherapeutic treatment is proven in colon cancer stage III (Dukes C) with levamisole and 5-FU. Completely resected rectal carcinoma should be treated postoperatively with combined radio-/chemotherapy. In the common clinical or practical setting, adjuvant therapy is indicated only in locally advanced gastrointestinal tumors following R{sub 0} resection. Postoperative therapy following incomplete tumor resection has its reason only in a palliative intention. (orig.) [Deutsch] Adjuvante Therapiestrategien sind wichtige flankierende Massnahmen der modernen onkologischen Chirurgie, da u.a. die 5-Jahres-Ueberlebensquoten bei lokal fortgeschrittenen Tumoren des Gastrointestinaltraktes nach wie vor unbefriedingend sind. Dabei muss grundsaetzlich zwischen adjuvanten Behandlungen nach kompletter Tumorexstirpation (UICC-R{sub 0}-Resektion) und der additiven Therapie nach palliativer Resektion (UICC-R{sub 1}- oder -R{sub 2}-Resektion) unterschieden werden. Als Modalitaeten kommen Chemotherapie, Strahlentherapie und ihre Kombination in Frage. Bei Oesophagus- und Magenkarzinomen kann derzeit keine gueltige Empfehlung zur adjuvanten Therapie gegeben werden. Die Radio

Cost-utility analysis of adjuvant chemotherapy in patients with stage III colon cancer in Thailand.

Science.gov (United States)

Lerdkiattikorn, Panattharin; Chaikledkaew, Usa; Lausoontornsiri, Wirote; Chindavijak, Somjin; Khuhaprema, Thirawud; Tantai, Narisa; Teerawattananon, Yot

2015-01-01

In Thailand, there has been no economic evaluation study of adjuvant chemotherapy for stage III colon cancer patients after resection. This study aims to evaluate the cost-utility of all chemotherapy regimens currently used in Thailand compared with the adjuvant 5-fluorouracil/leucovorin (5-FU/LV) plus capecitabine as the first-line therapy for metastatic disease in patients with stage III colon cancer after resection. A cost-utility analysis was performed to estimate the relevant lifetime costs and health outcomes of chemotherapy regimens based on a societal perspective using a Markov model. The results suggested that the adjuvant 5-FU/LV plus capecitabine as the first-line therapy for metastatic disease would be the most cost-effective chemotherapy. The adjuvant FOLFOX and FOLFIRI as the first-line treatment for metastatic disease would be cost-effective with an incremental cost-effectiveness ratio of 299,365 Thai baht per QALY gained based on a societal perspective if both prices of FOLFOX and FOLFIRI were decreased by 40%.

A model of the prescription-pharmaceutical sales process

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Michael Stros

2018-06-01

Full Text Available The purpose of this paper is to determine the factors in marketing most relevant to achieving pharmaceutical sales success and their interrelations, as well as providing a prescription-pharmaceuticals sales process model. This will enable scholars to obtain a better understanding of the marketing process for prescription pharmaceuticals, as well as enabling marketers to apply more efficient marketing approaches. The study uses a unique data set, combining primary data and secondary data from the Swiss prescription-pharmaceuticals market. The data is analysed using a multiple-regression based model. A multi-level data structure is found, suggesting that factors concerning the specific brand and also the pharmaceutical substance itself are relevant to sales success. It is revealed that the factors most relevant to sales success are: order of market entry, perceived product-quality, average price, and marketing expenditures, leading to practical recommendations for scholars and marketing professionals. The study focuses only on the Swiss prescription-pharmaceuticals market, investigating five medical drug classes. The assumption is made that these results can be generalised to similar markets and drug classes. The study develops a conceptual prescription-pharmaceuticals sales-process model; offers practical guidelines and a good basis for further scholarly research are provided; and identifies several research gaps by giving proposals for future research.

Renal Toxicity of Adjuvant Chemoradiotherapy With Cisplatin in Gastric Cancer

International Nuclear Information System (INIS)

Welz, Stefan; Hehr, Thomas; Kollmannsberger, Christian; Bokemeyer, Carsten; Belka, Claus; Budach, Wilfried

2007-01-01

Purpose: Adjuvant, 5-fluorouracil (5-FU)-based chemoradiotherapy for completely resected high-risk gastric adenocarcinoma has been shown to improve survival in a randomized Intergroup trial. However, the results still showed an unsatisfactory outcome. On the basis of previously reported results of a Phase II trial using a more aggressive, cisplatin-containing chemoradiotherapy schedule, we investigated the effects of this approach on long-term renal function. Patients and Methods: Between December 2000 and September 2003, 27 patients were treated at Tuebingen University in a Phase II multicenter trial investigating adjuvant chemoradiotherapy. The adjuvant chemoradiotherapy consisted of two cycles of adjuvant 5-FU, folinic acid, cisplatin (200 mg/m 2 ), and paclitaxel before and after radiotherapy (45 Gy in 1.8-Gy fractions) with daily concomitant 5-FU (225 mg/m 2 /24 h). A dose constraint of ≤12 Gy for 37.5% of the functional volume of both kidneys was used. Renal function was assessed by the changes in creatinine and creatinine clearance during follow-up. Results: The prescribed 45 Gy was administered to 100% of the patients, and the cumulative cisplatin dose was 200 mg/m 2 in 74% of all patients. In 89%, the constraints concerning the renal absorbed doses were met. The median follow-up for the creatinine and clearance values was 30 and 26 months, respectively. The creatinine values tended to worsen over time without reaching critical levels. We were unable to demonstrate a significant dose-response relationship for renal damage in the tested dose range. Conclusions: Using a dose constraint of ≤12 Gy for 37.5% of the functional volume of both kidneys appears to be safe at a median follow-up of 2 years for a cumulative cisplatin dose of 200 mg/m 2 administered before and after simultaneous 5-FU and radiotherapy

Toward a Regional Research Agenda on Pharmaceutical ...

International Development Research Centre (IDRC) Digital Library (Canada)

African policymakers are pushing for local pharmaceutical manufacturing as a ... Africa Development Community Pharmaceutical Business Plan (2007-2013) and ... IDRC congratulates first cohort of Women in Climate Change Science Fellows.

Concept of the Ural pharmaceutical cluster formation

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Aleksandr Petrovich Petrov

2011-06-01

Full Text Available This paper substantiates the necessity of cluster organization of the pharmaceutical industry in the region. The estimation of the state and prospects of development of such structures in the domestic economy is given. Sverdlovsk region was chosen as the object of study on the possibility of forming a pharmaceutical cluster. Objective prerequisites for the organization of a cluster of pharmaceutical production in Sverdlovsk region are considered, among these were distinguished: capacious and fast-growing market for pharmaceutical products, availability of potential development of the pharmaceutical industry in the territory and the key success factors for enterprises - potential participants of the cluster. Indicated key success factors are: presence of a creative team and close interaction between business and government, high level of cooperation among the enterprises of the cluster and commercialization of products, implementation of research and development expenditures etc. Thus, it was substantiated that in there all references and resources for the formation of a pharmaceutical cluster. The concept of formation and development of the Ural pharmaceutical cluster was elaborated. Inside the concept, the goals, objectives, processing, product and organizational priorities for cluster formation are identified. Architecture of this structure with a justification of its members and certain forms of interaction between them is proposed. The stages of formation and development of the Ural pharmaceutical cluster on the basis of a ten-year settlement period for the full range of activities for this project are substantiated. At each stage, a set of key objectives and results of the cluster was defined. The choice of phases was carried out on the basis of investment programs of cluster's enterprises strategic position on the mastering of markets and infrastructure development. An assessment of socio-economic efficiency of the Ural pharmaceutical

Adjuvant chemotherapy is associated with improved survival in patients with stage II colon cancer.

Science.gov (United States)

Casadaban, Leigh; Rauscher, Garth; Aklilu, Mebea; Villenes, Dana; Freels, Sally; Maker, Ajay V

2016-11-15

The role of adjuvant chemotherapy in patients with stage II colon cancer remains to be elucidated and its use varies between patients and institutions. Currently, clinical guidelines suggest discussing adjuvant chemotherapy for patients with high-risk stage II disease in the absence of conclusive randomized controlled trial data. To further investigate this relationship, the objective of the current study was to determine whether an association exists between overall survival (OS) and adjuvant chemotherapy in patients stratified by age and pathological risk features. Data from the National Cancer Data Base were analyzed for demographics, tumor characteristics, management, and survival of patients with stage II colon cancer who were diagnosed from 1998 to 2006 with survival information through 2011. Pearson Chi-square tests and binary logistic regression were used to analyze disease and demographic data. Survival analysis was performed with the log-rank test and Cox proportional hazards regression modeling. Propensity score weighting was used to match cohorts. Among 153,110 patients with stage II colon cancer, predictors of receiving chemotherapy included age clinically relevant OS was associated with the receipt of adjuvant chemotherapy in all patient subgroups regardless of high-risk tumor pathologic features (poor or undifferentiated histology, colon cancer evaluated to date, improved OS was found to be associated with adjuvant chemotherapy regardless of treatment regimen, patient age, or high-risk pathologic risk features. Cancer 2016;122:3277-3287. © 2016 American Cancer Society. © 2016 American Cancer Society.

Clinicopathological predictors of benefit from adjuvant chemotherapy for stage C colorectal cancer: Microsatellite unstable cases benefit.

Science.gov (United States)

Thomas, Michelle L; Hewett, Peter J; Ruszkiewicz, Andrew R; Moore, James W E

2015-12-01

In colorectal cancer (CRC), adjuvant therapy is offered on the basis of stage and attempts to identify factors to better target treatment have not been successful. Recent work suggested that mismatch repair deficient CRCs may not benefit from 5FU adjuvant chemotherapy but studies remain conflicting. We aimed to determine if gender, tumor site, tumor pathological characteristics and microsatellite instability (MSI) predict survival benefit from adjuvant chemotherapy in stage C CRC. Data were collated on ACPS (Australian Clinico-pathological Staging System) stage C CRC cases that underwent curative resection over a 23-year period. Pathology was reevaluated, DNA was extracted from the formalin-fixed paraffin specimen, and MSI status was established by BAT26 instability. Multivariate analysis was performed using Cox proportional hazard model and effects modification interaction testing. In total 814 unselected cases were included, of whom 37% received chemotherapy. Seventy-seven cases exhibited MSI. Overall, adjuvant chemotherapy produced a cancer-specific survival benefit (HR 0.52, 95% CI 0.39-0.70; P benefit. Chemotherapy was beneficial in both the MSI (HR 0.08, 95% CI 0.02-0.27; P = benefit from 5FU adjuvant chemotherapy for stage C CRC does not vary according to gender, site of tumor, pathological characteristics or MSI status. This study suggests that it would be unwise to exclude patients from being offered adjuvant chemotherapy on the basis of MSI. © 2015 The Authors. Asia-Pacific Journal of Clinical Oncology Published by Wiley Publishing Asia Pty Ltd.

Modelling of drying processes of pharmaceutical granules. Pharmaceutical Sciences for the Future of Medicines

DEFF Research Database (Denmark)

Mortier, S.T.F.C.; Vedantam, S.; De Beer, T.

Tablets are conventionally produced via consecutive batch process steps. Recent introduction of continuous process equipment is gaining industrial importance in pharmaceutics. Transition to continuous production requires improved understanding of all operations, necessitating the development...... of mechanistic models of multi‐phase systems which in the end allow process control. This contribution focuses on continuous fluidized bed drying of pharmaceutical wet granules. A stepwise approach is used in model development, starting with the drying behaviour of single granules. Experiments to determine...

[Assessment of the MF59-adjuvanted pandemic influenza A/H1N1 vaccine. Systematic review of literature].

Science.gov (United States)

Ruiz-Aragón, J; Grande Tejada, A M; Márquez-Peláez, S; Molina Linde, J M; Yang, R

2013-10-01

To assess the efficacy and safety of MF59-adjuvanted pandemic influenza A/H1N1 vaccine in children. A systematic review of the literature was performed after searching the MedLine and Embase electronic databases, and manual search in specialties journals, with MeSH terms and and free terms. Inclusion criteria were clinical trials with children vaccinated with MF59-adjuvanted influenza A/H1N1 vaccine, compared with other vaccines doses with/without MF59-adjuvanted. The immunogenicity and safety of the vaccine was recorded. The quality of the studies included was assessed by CASPe checklist. Four clinical trials with moderate quality were selected. The local and systemic adverse effects were rare and mild, with no differences between groups. Seroconversion and seroprotection levels were higher with MF59-adjuvanted vaccines. Antibody titres were also higher with the adjuvant vaccines. The adjuvant vaccine has a good efficacy and safety profile. The adverse effects that may occur are common and appear similarly in both vaccination groups. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Pharmaceutical product cross-contamination: industrial and clinical ...

African Journals Online (AJOL)

problems. Pharmaceutical product cross-contamination is a serious problem which has been detected as an obstacle ... In the pharmaceutical care of patients in developed countries, cross-contamination ..... neonatal intensive care units.

Quality Systems Implementation in the Pharmaceutical Industry

African Journals Online (AJOL)

Nafiisah

quality standards imposed on local pharmaceutical manufacturers. Keywords: Quality/ .... GMP is concerned with both production and quality control. It is aimed ... in the European pharmaceutical industry in designing their quality systems:.

The role of adjuvant platinum-based chemotherapy in esophagogastric cancer patients who received neoadjuvant chemotherapy prior to definitive surgery.

Science.gov (United States)

Saunders, John H; Bowman, Christopher R; Reece-Smith, Alex M; Pang, Vincent; Dorrington, Matthew S; Mumtaz, Errum; Soomro, Irshad; Kaye, Philip; Madhusudan, Srinivasan; Parsons, Simon L

2017-06-01

For patients with operable esophagogastric cancer, peri-operative chemotherapy confers a significant overall survival benefit compared to surgery alone, however only 30-40% of patients demonstrate histopathological response. It is unclear whether those with no neoadjuvant chemotherapy response should go onto receive adjuvant chemotherapy, as no further benefit may be conferred. Esophagogastric cancers were prospectively captured with associated histopathological tumor regression grades following neoadjuvant chemotherapy. This cohort was then interrogated for clinico-pathological and survival outcomes. Following neoadjuvant chemotherapy and surgery, patients with chemotherapy responsive cancers, who were administered adjuvant chemotherapy gained a significant overall survival benefit. Multivariate Cox analysis, demonstrated a final adjusted hazard ratio for adjuvant therapy of 0.509; (95%CI 0.28-0.93); P = 0.028. In contrast, patients with non-responsive tumors, who underwent adjuvant chemotherapy, did not show any survival benefit. Chemotherapy toxicity was prevalent and contributed to only half of patients receiving adjuvant chemotherapy. These results suggest the benefit of the adjuvant portion of chemotherapy is limited to those who demonstrate a histopathological response to neoadjuvant chemotherapy. The administration of the adjuvant portion of chemotherapy to patients without a response to neoadjuvant chemotherapy may not provide any survival benefit, while potentially causing increased morbidity. © 2017 Wiley Periodicals, Inc.

PHARMACEUTICAL COMPANIES BETWEEN CRISIS AND COMPETITIVENESS - SECTORAL DIAGNOSIS

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Mihaela\tBÎRSAN

2015-06-01

Full Text Available The evolution of the pharmaceutical industry was a positive constant with the indicators of industrial production even in years of crisis. Although the economic crisis in Romania decreased average growth rate of pharmaceutical companies, market value is expected to increase. The explanation comes from the fact that in order to boost productivity, pharmaceutical companies are turning to emerging countries with aging populations such as open new markets for future development. Add to this the recent health policies implemented by newly industrialized countries that are aimed at ensuring increased access to care. Analysts see the field phenomenon called "Farma-merger" a good chance for European pharmaceutical companies oriented to developing countries where drug sales should record a double-digit annual growth until 2017. In Erste Group reports stated that the impact of the crisis on the pharmaceutical industry should be limited markets for EU only their economic slowdown. This will be possible because the external indebtedness of pharmaceutical companies in the EU remains at a minimum, they are able to finance their investment plans without tapping financial markets, are not adversely affected by the current limited availability of credit resources. Therefore major pharmaceutical companies in the EU will remain a solid investment on the long term, the negative developments are limited due to high resistance to the crisis their business model segment "generic". The consequence of these developments is reflected in the recognition for the first time, the pharmaceutical sector as a strategic sector for the Romanian economy. In the context of public debate launching the National Strategy for Competitiveness 2014-2020, Generic Medicines Industry Association of Romania (APMGR local pharmaceutical industry reminds the Government proposals on correcting the current fiscal and operational regulatory framework, to allow unlocking investments in facilities

Cost benefit of investment on quality in pharmaceutical manufacturing: WHO GMP pre- and post-certification of a Nigerian pharmaceutical manufacturer.

Science.gov (United States)

Anyakora, Chimezie; Ekwunife, Obinna; Alozie, Faith; Esuga, Mopa; Ukwuru, Jonathan; Onya, Steve; Nwokike, Jude

2017-09-18

Pharmaceutical companies in Africa need to invest in both facilities and quality management systems to achieve good manufacturing practice (GMP) compliance. Compliance to international GMP standards is important to the attainment of World Health Organization (WHO) prequalification. However, most of the local pharmaceutical manufacturing companies may be deterred from investing in quality because of many reasons, ranging from financial constraints to technical capacity. This paper primarily evaluates benefits against the cost of investing in GMP, using a Nigerian pharmaceutical company, Chi Pharmaceuticals Limited, as a case study. This paper also discusses how to drive more local manufacturers to invest in quality to attain GMP compliance; and proffers practical recommendations for local manufacturers who would want to invest in quality to meet ethical and regulatory obligations. The cost benefit of improving the quality of Chi Pharmaceuticals Limited's facilities and system to attain WHO GMP certification for the production of zinc sulfate 20-mg dispersible tablets was calculated by dividing the annual benefits derived from quality improvement interventions by the annual costs of implementing quality improvement interventions, referred to as a benefit-cost ratio (BCR). Cost benefit of obtaining WHO GMP certification for the production of zinc sulfate 20-mg dispersible tablets was 5.3 (95% confidence interval of 5.0-5.5). Investment in quality improvement intervention is cost-beneficial for local manufacturing companies. Governments and regulators in African countries should support pharmaceutical companies striving to invest in quality. Collaboration of local manufacturing companies with global companies will further improve quality. Local pharmaceutical companies should be encouraged to key into development opportunities available for pharmaceutical companies in Africa.

A new e-beam application in the pharmaceutical industry

International Nuclear Information System (INIS)

Sadat, Theo; Malcolm, Fiona

2005-01-01

The paper presents a new electron beam application in the pharmaceutical industry: an in-line self-shielded atropic transfer system using electron beam for surface decontamination of products entering a pharmaceutical filling line. The unit was developed by Linac Technologies in response to the specifications of a multi-national pharmaceutical company, to solve the risk of microbial contamination entering a filling line housed inside an isolator. In order to fit the sterilization unit inside the pharmaceutical plant, a 'miniature' low-energy (200 keV) electron beam accelerator and e-beam tunnel were designed, all conforming to the pharmaceutical good manufacturing practice (GMP) regulations. Process validation using biological indicators is described, with reference to the regulations governing the pharmaceutical industry. Other industrial applications of a small-sized self-shielded electron beam sterilization unit are mentioned

DNA Vaccine Electroporation and Molecular Adjuvants

Science.gov (United States)

2016-03-16

Suschak and Schmaljohn DNA Vaccine Electroporation and Molecular Adjuvants 1 Abstract To date, there is no protective vaccine for Ebola virus...the formulation of DNA launched virus-like particles (VLP). In this case, the antigen is encoded in one DNA plasmid, while structural proteins are...Virol, 2010. 155(12): p. 2083-103. 2. Feldmann, H. and T.W. Geisbert, Ebola haemorrhagic fever. Lancet, 2011. 377(9768): p. 849-62. 3. Hart, M.K

Nanoparticulate Tubular Immunostimulating Complexes: Novel Formulation of Effective Adjuvants and Antigen Delivery Systems

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Nina Sanina

2017-01-01

Full Text Available New generation vaccines, based on isolated antigens, are safer than traditional ones, comprising the whole pathogen. However, major part of purified antigens has weak immunogenicity. Therefore, elaboration of new adjuvants, more effective and safe, is an urgent problem of vaccinology. Tubular immunostimulating complexes (TI-complexes are a new type of nanoparticulate antigen delivery systems with adjuvant activity. TI-complexes consist of cholesterol and compounds isolated from marine hydrobionts: cucumarioside A2-2 (CDA from Cucumaria japonica and monogalactosyldiacylglycerol (MGDG from marine algae or seagrass. These components were selected due to immunomodulatory and other biological activities. Glycolipid MGDG from marine macrophytes comprises a high level of polyunsaturated fatty acids (PUFAs, which demonstrate immunomodulatory properties. CDA is a well-characterized individual compound capable of forming stable complex with cholesterol. Such complexes do not possess hemolytic activity. Ultralow doses of cucumariosides stimulate cell as well as humoral immunity. Therefore, TI-complexes comprising biologically active components turned out to be more effective than the strongest adjuvants: immunostimulating complexes (ISCOMs and complete Freund’s adjuvant. In the present review, we discuss results published in series of our articles on elaboration, qualitative and quantitative composition, ultrastructure, and immunostimulating activity of TI-complexes. The review allows immersion in the history of creating TI-complexes.

Pharmaceutical regulation in 15 European countries review.

Science.gov (United States)

Panteli, Dimitra; Arickx, Francis; Cleemput, Irina; Dedet, Guillaume; Eckhardt, Helen; Fogarty, Emer; Gerkens, Sophie; Henschke, Cornelia; Hislop, Jennifer; Jommi, Claudio; Kaitelidou, Daphne; Kawalec, Pawel; Keskimaki, Ilmo; Kroneman, Madelon; Lopez Bastida, Julio; Pita Barros, Pedro; Ramsberg, Joakim; Schneider, Peter; Spillane, Susan; Vogler, Sabine; Vuorenkoski, Lauri; Wallach Kildemoes, Helle; Wouters, Olivier; Busse, Reinhard

2016-10-01

In the context of pharmaceutical care, policy-makers repeatedly face the challenge of balancing patient access to effective medicines with affordability and rising costs. With the aim of guiding the health policy discourse towards questions that are important to actual and potential patients, this study investigates a broad range of regulatory measures, spanning marketing authorization to generic substitution and resulting price levels in a sample of 16 European health systems (Austria, Belgium, Denmark, England, Finland, France, Germany, Greece, Ireland, Italy, the Netherlands, Poland, Portugal, Scotland, Spain and Sweden). All countries employ a mix of regulatory mechanisms to contain pharmaceutical expenditure and ensure quality and efficiency in pharmaceutical care, albeit with varying configurations and rigour. This variation also influences the extent of publicly financed pharmaceutical costs. Overall, observed differences in pharmaceutical expenditure should be interpreted in conjunction with the differing volume and composition of consumption and price levels, as well as dispensation practices and their impact on measurement of pharmaceutical costs. No definitive evidence has yet been produced on the effects of different cost-containment measures on patient outcomes. Depending on the foremost policy concerns in each country, different levers will have to be used to enable the delivery of appropriate care at affordable prices. World Health Organization 2016 (acting as the host organization for, and secretariat of, the European Observatory on Health Systems and Policies).

Depression related to (neo)adjuvant hormonal therapy for prostate cancer

International Nuclear Information System (INIS)

Tol-Geerdink, Julia J. van; Leer, Jan Willem; Lin, Emile N.J.T. van; Schimmel, Erik C.; Stalmeier, Peep F.M.

2011-01-01

Background: We studied whether hormonal therapy, (neo)adjuvant to radiotherapy for localized prostate cancer, is related to an increase in depression and whether this is caused by the hormonal therapy itself or by the relatively poor prognosis of patients who get (neo)adjuvant hormonal therapy. Methods: Between 2002 and 2005, 288 patients, irradiated for prostate cancer (T1-3N0M0), were studied prospectively in two clinics. In one clinic almost all patients received (neo)adjuvant androgen deprivation (Bicalutamide + Gosereline). In a second clinic hormonal therapy was prescribed mainly for high risk patients. This allowed us to separate the effects of hormonal therapy and the patient's prognosis. Results: During the course of hormonal therapy, depression was significantly heightened by both hormone use (p < 0.001) and poor prognosis (p < 0.01). After completion of hormonal therapy, poor prognosis continued to affect the depression score (p < 0.01). The increase was, however, small. Conclusions: Depression was mildly increased in patients receiving hormonal therapy. The increase appeared to be related to both the hormone therapy itself and the high risk status of patients. High risk status, with the associated poor prognosis, had a more sustained effect on depression. The rise was statistically significant, but was too small, however, to bear clinical significance.

STRAP Is a Strong Predictive Marker of Adjuvant Chemotherapy Benefit in Colorectal Cancer

OpenAIRE

Buess, Martin; Terracciano, Luigi; Reuter, Jurgen; Ballabeni, Pierluigi; Boulay, Jean-Louis; Laffer, Urban; Metzger, Urs; Herrmann, Richard; Rochlitz, Christoph

2004-01-01

BACKGROUND: Molecular predictors for the effectiveness of adjuvant chemotherapy in colorectal cancer are of considerable clinical interest. To this aim, we analyzed the serine threonine receptor-associated protein (STRAP), an inhibitor of TGF-βsignaling, with regard to prognosis and prediction of adjuvant 5-FU chemotherapy benefit. i The gene copy status of STRAP was determined using quantitative realtime polymerase chain reaction in 166 colorectal tumor biopsies, which had been collected fro...

Evaluation Effect of Adjuvant on Mesosulfuron+Iodosulfuron Herbicide Performance on Littleseed Canarygrass Control

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M. kargar

2016-02-01

Full Text Available Introduction: Adjuvant application is one of the most important ways to increase herbicide efficacy and decrease environmental damaging effects of herbicides. In general, It has displayed that a very few of the spray droplets retained on the surface of leaf plants and the majority of them bounce off the leaf surface. Therefore, in spraying processes, adjuvant designed to enhance the absorbing, emulsifying, dispersing, spreading, sticking, wetting, or penetrating properties of pesticides. Adjuvant are most often used with herbicides to help a pesticide spread over a leaf surface and penetrate the waxy cuticle of a leaf or to penetrate through the small hairs present on a leaf surface. Surfactants and crop oils are two types of adjuvant that are used for increasing efficacy of herbicides. In many cases, significant increases have been observed in biological activity with the addition of surfactants or crop oils. For example, the performance of specific graminicides and some sulfonylureas is usually increased by the addition of tank-mix oils. It is generally accepted that the benefit of oils is related to their ability to increase the drying period of droplets during their fly time before their impact on the plants, to improve the spreading of the deposit on difficult-to-wet targets (mainly Graminaceae, to act as solubilizing agents, and above all to enhance the penetration of herbicides into the plants. Among commercially available adjuvants, emulsified vegetable oils have been shown to increase droplet retention and spreading, and enhance absorption and translocation of active ingredients. It has been reported that efficacy of atrazine, bentazone, phenmedipham and rimsulfuron on various weeds were increased by the addition of rapeseed oils to solution spray. Materials and Methods: In order to evaluate the effect of adjuvant concentrations on surface tension of aqueous solutions, an experiment was conducted as completely randomized design with 4

Cleaner production at pharmaceutical industry: first steps assessment

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Edilaine Conceição Rezende

2015-12-01

Full Text Available The Cleaner Production (CP is an environmental management system effective to comply the environmental obligations and promote sustainable development of enterprises. In this study, the implementing possibilities of CP practices were evaluated to pharmaceutical industry, through prior identification procedures for Pharmaceutical Manufacturing Practices. The study was conducted in a scientific and health care institution, which produces pharmaceutical drugs and makes assistance for public health. The production process was evaluated and made a survey of the main points of waste and sewage generations in each stage, in order to diagnose the measures of CP established and propose new actions. Thus, by using this tool, it was possible to demonstrate the reduction of environmental impacts associated with pharmaceutical production. The Pharmaceutical Manufacturing Practices also contributed to the implementation of measures CP, preserving the final product quality, and generating environmental and economic benefits.

A cost-effectiveness analysis of adjuvant therapies for resected adenocarcinoma of the rectum

International Nuclear Information System (INIS)

Lee, Jason H.

1997-01-01

PURPOSE: Several prospective randomized trials have shown a significant survival advantage with adjuvant chemotherapy and radiation therapy following surgical resection of adenocarcinoma of the rectum. Recent and ongoing trials are evaluating the role of modulated and/or protracted venous infusion [PVI] chemotherapy with pelvic irradiation [PRT]. The economic implications of additional therapies compared with their incremental benefits have not been rigorously analyzed. This study attempts to assess the incremental cost effectiveness of adjuvant therapy over surgery alone, and secondly, adjuvant therapy with PVI delivery systems versus rapid infusion. METHODS: A Markov model was constructed to describe the natural history of rectal carcinoma [stage B2, C] following surgical resection in a hypothetical cohort of 60 year old patients. This model was used to perform two sets of comparisons: [1] surgery alone versus adjuvant bolus fluorouracil [5-FU] with PRT, and [2] bolus 5-FU with PRT versus PVI 5-FU with PRT. Relapse rates and overall survival were derived from an early GITSG trial for the first comparison and from the NCCTG 86-47-51 trial for the second comparison. Medicare reimbursement rates and reports from health maintenance organizations were used to obtain net medical costs of adjuvant treatments, routine follow-up, advanced recurrent disease, and terminal illness as a result of rectal carcinoma. Total years of life and medical costs were projected over an 8-year time horizon for the first comparison [GITSG data] and over a 5-year time horizon for the second comparison [NCCTG data]. Monetary and nonmonetary benefits were discounted at 5% per year. Adjustments for quality of life, costs of adverse effects from treatment, and indirect costs of disease or treatment were not included in this current analysis. RESULTS: The main survival and economic outcomes for each treatment arm in the two comparisons are reported in the table below. For the first comparison

Pharmaceutical services and health promotion: how far have we gone and how are we faring? Scientific output in pharmaceutical studies

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Carina Akemi Nakamura

2014-12-01

Full Text Available The objective of this study was to investigate the scientific output on health promotion within the pharmaceutical field and its relation with the development of pharmaceutical services within health systems. A comprehensive review of published scientific articles from the Medline and Lilacs databases was carried out. The review comprised articles published until December 2011, and used combinations of the terms 'health promotion' or 'health education' and 'pharmacy', 'pharmacist' or 'pharmaceutical'. The articles were selected according to inclusion and exclusion criteria. A total of 170 full texts and 87 indexed abstracts were analyzed, evidencing that most described actions of health promotion in community pharmacies and other services. Following the Ottawa Charter, most of the studies dealt with new guidance of the service and the supply of pharmaceutical information and services. It was concluded that there is a lack of theoretical background on health promotion in the pharmaceutical field to sustain the professional education and practice required by the health system and the population.

[Study on processing adjuvant medicines in Lei Gong's treatise on preparation and broiling of materia medica (Leigong Paozhi Lun)].

Science.gov (United States)

Zhang, Wei; Zhang, Ruixian

2010-09-01

There were 268 kinds of medicines recorded in the book of Lei Gong's Treatise on preparation and broiling of materia medica (Leigong Paozhi Lun). Among these medicines, 178 medicines were prepared with adjuvant medicines, including general and special compatible adjuvant medicines. These adjuvant medicines used in this book can be explained by the theory of "seven-relation compatibility". The author tried to explain the usage and their compatibility of these adjuvant medicines and put forward that attention should be paid to the changes in functions of medicines and the influences of society should be paid attention.

East and Central African Journal of Pharmaceutical Sciences An ...

African Journals Online (AJOL)

An Approach to Effective Disinfection of Salon Items [clippers, combs and scissors]. O.S. OLONITOLA'*, P.F. OLURINOLA~ ... 2~epartment of Pharmaceutics and Pharmaceutical Microbiology, Faculty of Pharmaceutical. Sciences, Ahmadu Bello ... antimicrobial products with increased value over those currently available.

The use of atomic spectroscopy in the pharmaceutical industry for the determination of trace elements in pharmaceuticals.

Science.gov (United States)

Lewen, Nancy

2011-06-25

The subject of the analysis of various elements, including metals and metalloids, in the pharmaceutical industry has seen increasing importance in the last 10-15 years, as modern analytical instrumentation has afforded analysts with the opportunity to provide element-specific, accurate and meaningful information related to pharmaceutical products. Armed with toxicological data, compendial and regulatory agencies have revisited traditional approaches to the testing of pharmaceuticals for metals and metalloids, and analysts have begun to employ the techniques of atomic spectroscopy, such as flame- and graphite furnace atomic absorption spectroscopy (FAAS, Flame AA or FAA and GFAAS), inductively coupled plasma-atomic emission spectroscopy (ICP-AES) and inductively coupled plasma-mass spectrometry (ICP-MS), to meet their analytical needs. Newer techniques, such as laser-induced breakdown spectroscopy (LIBS) and Laser Ablation ICP-MS (LAICP-MS) are also beginning to see wider applications in the analysis of elements in the pharmaceutical industry.This article will provide a perspective regarding the various applications of atomic spectroscopy in the analysis of metals and metalloids in drug products, active pharmaceutical ingredients (API's), raw materials and intermediates. The application of atomic spectroscopy in the analysis of metals and metalloids in clinical samples, nutraceutical, metabolism and pharmacokinetic samples will not be addressed in this work. Copyright © 2010 Elsevier B.V. All rights reserved.

Survival Benefit of Adjuvant Radiation Therapy for Gastric Cancer following Gastrectomy and Extended Lymphadenectomy

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R. A. Snyder

2012-01-01

Full Text Available Purpose. Although randomized trials suggest a survival benefit of adjuvant chemotherapy and radiation therapy (XRT for gastric adenocarcinoma, its use in patients who undergo an extended lymphadenectomy is less clear. The purpose of this study was to determine if a survival benefit exists in gastric cancer patients who receive adjuvant XRT following resection with extended lymphadenectomy. Methods. The SEER registry was queried for records of patients with resected gastric adenocarcinoma from 1988 to 2007. Multivariable Cox regression models were used to assess independent prognostic factors affecting overall survival (OS and disease-specific survival (DSS. Results. Of 15,060 patients identified, 3,208 (21% received adjuvant XRT. Adjuvant XRT was independently associated with improved OS (HR 0.67, CI 0.64–0.71 and DSS (HR 0.69, CI 0.65–0.73 in stages IB through IV (M0. This OS and DSS benefit persisted regardless of the extent of lymphadenectomy. Furthermore, lymphadenectomy with >25 LN resected was associated with improved OS and DSS compared with 25 LNs results in improved OS and DSS compared with patients who have fewer LNs resected.

Colorectal signet-ring cell carcinoma: benefit from adjuvant chemotherapy but a poor prognostic factor.

Science.gov (United States)

Hugen, Niek; Verhoeven, Rob H; Lemmens, Valery E; van Aart, Carola J; Elferink, Marloes A; Radema, Sandra A; Nagtegaal, Iris D; de Wilt, Johannes H

2015-01-15

Colorectal signet-ring cell carcinoma (SRCC) has been associated with poor survival compared with mucinous adenocarcinoma (MC) and the more common adenocarcinoma (AC). Efficacy of adjuvant chemotherapy in SRCC has never been assessed. This study analyzes the prognostic impact of SRCC and determines whether colonic SRCC patients benefit from adjuvant chemotherapy equally compared with MC and AC patients. Data on 196,757 colorectal cancer (CRC) patients in the period 1989-2010 was included in this Dutch nationwide population-based study. Five-year relative survival estimates were calculated and multivariate relative survival analyses using a multiple regression model of relative excess risk (RER) were performed. SRCC was found in 1,972 (1.0%) patients. SRCC patients presented more frequently with stage III or IV disease than AC patients (75.2% vs. 43.6%, p chemotherapy (RER 1.10, 95% CI 0.81-1.51), suggesting a comparable benefit from adjuvant chemotherapy in AC and SRCC. In conclusion, the prognostic impact of SRCC is dismal in both colon and rectal cancer patients, but adjuvant chemotherapy is associated with improved survival in AC, MC, and SRCC patients. © 2014 UICC.

Antibody-antigen-adjuvant conjugates enable co-delivery of antigen and adjuvant to dendritic cells in cis but only have partial targeting specificity

NARCIS (Netherlands)

Kreutz, M.; Giquel, B.; Hu, Q.; Abuknesha, R.; Uematsu, S.; Akira, S.; Nestle, F.O.; Diebold, S.S.

2012-01-01

Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC) by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is

Pharmaceutical policy and the lay public

DEFF Research Database (Denmark)

Traulsen, Janine Marie; Almarsdóttir, Anna Birna

2005-01-01

Almost every national and supranational health policy document accords high importance to the need to listen to and 'empower' patients. The relationship between pharmaceutical policy and the lay public is not direct but mediated by several actors, including health care workers, patient organisati......Almost every national and supranational health policy document accords high importance to the need to listen to and 'empower' patients. The relationship between pharmaceutical policy and the lay public is not direct but mediated by several actors, including health care workers, patient...... organisations, industry and, most recently, the media. Although the overall aim of health and pharmaceutical policy is to address the needs of all citizens, there are only a few, well organised groups who are actually consulted and involved in the policymaking process, often with the support of the industry....... The reasons for this lack of citizen involvement in health and pharmaceutical policymaking are many, for example: there is no consensus about what public involvement means; there is a predominance of special interest groups with narrow, specific agendas; not all decision makers welcome lay participation...

Antibody and T-cell responses to a virosomal adjuvanted H9N2 avian influenza vaccine: impact of distinct additional adjuvants

NARCIS (Netherlands)

Radosević, Katarina; Rodriguez, Ariane; Mintardjo, Ratna; Tax, Dennis; Bengtsson, Karin Lövgren; Thompson, Catherine; Zambon, Maria; Weverling, Gerrit Jan; Uytdehaag, Fons; Goudsmit, Jaap

2008-01-01

A highly efficacious vaccine is required to counteract a threat of an avian influenza pandemic. Increasing the potency of vaccines by adjuvation is essential not only to overcome generally low immunogenicity of pandemic strains, but also to allow dose sparing and as such to make it feasible to

Pharmaceutical care in the Netherlands. History, definition and projects

NARCIS (Netherlands)

van Mil, J.W F

1996-01-01

The evolving concept of Pharmaceutical Care knows different interpretations in a different countries. In the Netherlands community pharmacists already perform several functions which may be part of the Pharmaceutical Care concept. The Dutch concept of Pharmaceutical care is tested in the TOM and

[Benefit of adjuvant 5-fluorouracil based chemotherapy for colon cancer: a retrospective cohort study].

Science.gov (United States)

Mondaca, Sebastián; Villalón, Constanza; Leal, José Luis; Zúñiga, Álvaro; Bellolio, Felipe; Padilla, Oslando; Palma, Silvia; Garrido, Marcelo; Nervi, Bruno

2016-02-01

Multiple clinical trials have demonstrated the benefits of adjuvant 5-fluorouracil-based chemotherapy for patients with resectable colon cancer (CC), especially in stage III. To describe the clinical characteristics of a cohort of CC patients treated at a single university hospital in Chile since 2002, and to investigate if chemotherapy had an effect on survival rates. Review of a tumor registry of the hospital. Medical records of patients with CC treated between 2002 and 2012 were reviewed. Death certificates from the National Identification Service were used to determine mortality. Overall survival was described using the Kaplan-Meier method. A multivariate Cox proportional hazard regression model was also used. A total of 370 patients were treated during the study period (202 in stage II and 168 in stage III). Adjuvant chemotherapy was administered to 22 and 70% of patients in stage II and III respectively. The median follow-up period was 4.6 years. The 5-year survival rate for stage II patients was 79% and there was no benefit observed with adjuvant chemotherapy. For stage III patients, the 5-year survival rate was 81% for patients who received adjuvant chemotherapy, compared to 56% for those who did not receive chemotherapy (hazard ratio (HR): 0.29; 95% confidence interval (CI): 0.15-0.56). The benefit of chemotherapy was found to persist after adjustment for other prognostic variables (HR: 0.47; 95% CI: 0.23-0.94). Patients with colon cancer in stage III who received adjuvant chemotherapy had a better overall survival.

Dose-tailoring of FEC adjuvant chemotherapy based on leukopenia is feasible and well tolerated. Toxicity and dose intensity in the Scandinavian Breast Group phase 3 adjuvant Trial SBG 2000-1

DEFF Research Database (Denmark)

Edlund, Per; Ahlgren, Johan; Bjerre, Karsten

2011-01-01

The SBG 2000-1 trial is a randomised study that investigates if dose-tailored adjuvant FEC therapy based on the individual's leukocyte nadir value can improve outcome. The study has included 1535 women with medium and high-risk breast cancer.......The SBG 2000-1 trial is a randomised study that investigates if dose-tailored adjuvant FEC therapy based on the individual's leukocyte nadir value can improve outcome. The study has included 1535 women with medium and high-risk breast cancer....

Pharmaceutical new product development: the increasing role of in-licensing.

Science.gov (United States)

Edwards, Nancy V

2008-12-01

Many pharmaceutical companies are facing a pipeline gap because of the increasing economic burden and uncertainty associated with internal research and development programs designed to develop new pharmaceutical products. To fill this pipeline gap, pharmaceutical companies are increasingly relying on in-licensing opportunities. New business development identifies new pharmaceuticals that satisfy unmet needs and are a good strategic fit for the company, completes valuation models and forecasts, evaluates the ability of the company to develop and launch products, and pursues in-licensing agreements for pharmaceuticals that cannot be developed internally on a timely basis. These agreements involve the transfer of access rights for patents, trademarks, or similar intellectual property from an outside company in exchange for payments. Despite the risks, in-licensing is increasingly becoming the preferred method for pharmaceutical companies with pipeline gaps to bring new pharmaceuticals to the clinician.

Care ideologies reflected in 4 conceptions of pharmaceutical care.

Science.gov (United States)

Björkman, Ingeborg K; Bernsten, Cecilia B; Sanner, Margareta A

2008-12-01

Different ways to practice pharmaceutical care have been developed. One expression of this fact is the existence of many different classification systems to document drug-related problems (DRPs). Evidence suggests that classification systems have different characteristics and that these characteristics reflect different conceptions of pharmaceutical care. To increase the understanding of conceptions of pharmaceutical care, underlying values and beliefs (ideologies) can be explored. To explore various conceptions of pharmaceutical care to identify the care ideologies on which these conceptions are based. Representatives of 4 selected conceptions of pharmaceutical care were interviewed in face-to-face meetings. During the interviews, 4 basic questions were asked. Three were focused on pharmaceutical care and 1 on DRPs. Interview transcripts were analyzed by an inductive method inspired by grounded theory. The conceptions studied were Strand, Granada-II, PCNE v5.0, and Apoteket. In Strand, patients are given a more active role in the pharmaceutical care process, as compared to Granada-II, PCNE v5.0, and Apoteket. Pharmacists in all the conceptions of pharmaceutical care assume they have special knowledge that patients benefit from. However, they use their knowledge in different ways in the various pharmaceutical care conceptions. In Strand, individual goals of drug therapy are established together with the patient, whereas in Granada-II, PCNE, and Apoteket goals are not explicitly discussed. The identified differences correspond to different care ideologies. The pharmaceutical care conceptions are based on different care ideologies. The ideology is expressed in how therapy goals are set and patient needs defined. Strand is based on a patient-centered ideology; patient therapy goals and needs are defined by the patient together with the practitioners. Granada-II, PCNE, and Apoteket are based on an evidence-based medicine approach; patient therapy goals and needs are

Cell-Based Veterinary Pharmaceuticals - Basic Legal Parameters Set by the Veterinary Pharmaceutical Law and the Genetic Engineering Law of the European Union.

Science.gov (United States)

Faltus, Timo; Brehm, Walter

2016-01-01

Cell-based therapies have been in use in veterinary medicine for years. However, the legal requirement of manufacturing, placing on the market and use of cell-based veterinary pharmaceuticals are not as well developed as the respective requirements of chemical pharmaceuticals. Cell-based veterinary pharmaceuticals are medicinal products in the sense of the pharmaceutical law of the European Union (EU). For that reason, such medicinal products principally require official approval for their manufacture and an official marketing authorization for their placement on the market before being used by the veterinarian. The manufacture, placing on the market, and use of cell-based veterinary pharmaceuticals without manufacturing approval and marketing authorization is permitted only in certain exceptional cases determined by EU and individual Member State law. Violations of this requirement may have consequences for the respective veterinarian under criminal law and under the code of professional conduct in the respective Member State. The regular use of cell-based veterinary pharmaceuticals within the scope of a therapeutic emergency as well as the import of such veterinary pharmaceuticals from non-European countries for use in the EU are currently out of the question in the EU because of a lack of legal bases. Here, we review the general legal requirement of manufacturing, placing on the market, and use of cell-based veterinary pharmaceuticals within the EU and point out different implementations of EU law within the different Member States.

Supercritical fluid technology: concepts and pharmaceutical applications.

Science.gov (United States)

Deshpande, Praful Balavant; Kumar, G Aravind; Kumar, Averineni Ranjith; Shavi, Gopal Venkatesh; Karthik, Arumugam; Reddy, Meka Sreenivasa; Udupa, Nayanabhirama

2011-01-01

In light of environmental apprehension, supercritical fluid technology (SFT) exhibits excellent opportunities to accomplish key objectives in the drug delivery sector. Supercritical fluid extraction using carbon dioxide (CO(2)) has been recognized as a green technology. It is a clean and versatile solvent with gas-like diffusivity and liquid-like density in the supercritical phase, which has provided an excellent alternative to the use of chemical solvents. The present commentary provides an overview of different techniques using supercritical fluids and their future opportunity for the drug delivery industry. Some of the emerging applications of SFT in pharmaceuticals, such as particle design, drug solubilization, inclusion complex, polymer impregnation, polymorphism, drug extraction process, and analysis, are also covered in this review. The data collection methods are based on the recent literature related to drug delivery systems using SFT platforms. SFT has become a much more versatile and environmentally attractive technology that can handle a variety of complicated problems in pharmaceuticals. This cutting-edge technology is growing predominantly to surrogate conventional unit operations in relevance to the pharmaceutical production process. Supercritical fluid technology has recently drawn attention in the field of pharmaceuticals. It is a distinct conception that utilizes the solvent properties of supercritical fluids above their critical temperature and pressure, where they exhibit both liquid-like and gas-like properties, which can enable many pharmaceutical applications. For example, the liquid-like properties provide benefits in extraction processes of organic solvents or impurities, drug solubilization, and polymer plasticization, and the gas-like features facilitate mass transfer processes. It has become a much more versatile and environmentally attractive technology that can handle a variety of complicated problems in pharmaceuticals. This review is

A strategy to improve skills in pharmaceutical supply management in East Africa: the regional technical resource collaboration for pharmaceutical management

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Minzi Omary

2008-12-01

Full Text Available Abstract Background International initiatives such as the Global Fund to Fight AIDS, Tuberculosis and Malaria, the President's Emergency Plan for AIDS Relief and the President's Malaria Initiative have significantly increased availability and access to medicines in some parts of the developing world. Despite this, however, skills remain limited on quantifying needs for medications and ordering, receiving and storing medications appropriately; recording medications inventories accurately; distributing medications for use appropriately; and advising patients on how to use medications appropriately. The Regional Technical Resource Collaboration for Pharmaceutical Management (RTRC has been established to help address the problem of skills shortage in pharmaceutical management in East Africa. Methods The initiative brings together academic institutions from four East African countries to participate in skills-building activities in pharmaceutical supply management. The initiative targeted the institutions' ability to conduct assessments of pharmaceutical supply management systems and to develop and implement effective skills-building programmes for pharmaceutical supply chain management. Results Over a two-year period, the RTRC succeeded in conducting assessments of pharmaceutical supply management systems and practices in Kenya, Rwanda, Tanzania and Uganda. In 2006, the RTRC participated in a materials-development workshop in Kampala, Uganda, and contributed to the development of comprehensive HIV/AIDS pharmaceutical management training materials; these materials are now widely available in all four countries. In Tanzania and Uganda the RTRC has been involved with the training of health care workers in HIV/AIDS pharmaceutical management. In Kenya, Tanzania and Uganda the RTRC has been conducting operations research to find solutions to their countries' skills-shortage problems. Some of the interventions tested include applying and evaluating the

Internet pharmaceutical sales: attributes, concerns, and future forecast.

Science.gov (United States)

Bruckel, Katy; Capozzoli, Ernest A

2003-01-01

Internet pharmaceutical sales continue to skyrocket as healthcare providers and consumers are increasingly relying on the efficiencies and convenience that is available via such transactions. Managed care companies, increasing demands to reduce healthcare inefficiencies while maximizing the quality of patient care is a significant contributing factor to the expanding utilization and success of online pharmaceutical sales. However, with the expansion of Internet pharmaceutical sales, healthcare providers, pharmacy benefit management and insurance companies, and consumers realize new opportunities and risks. This paper will review the attributes and concerns associated with online pharmaceutical sales, discussing current and pending legislation intended to more effectively manage these parameters.

Adjuvant Therapy for Thymic Carcinoma--A Decade of Experience in a Taiwan National Teaching Hospital.

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Yen-Han Tseng

Full Text Available Thymic carcinomas are rare tumors for which surgical resection is the first treatment of choice. The role of adjuvant treatment after surgery is unknown because of limited available data. The present study evaluated the efficacy of post-surgery adjuvant chemotherapy or radiotherapy in patients with thymic carcinoma.To evaluate the role of adjuvant therapy in patients with thymic carcinoma, we retrospectively reviewed the records of patients with thymic carcinoma who were diagnosed and treated between 2004 and 2014.Among 78 patients with thymic carcinoma, 30 patients received surgical resection. Progression-free survival (PFS and overall survival (OS were significantly longer among these patients than among patients who received other treatments (PFS: 88.4 months vs 9.1 months, p<0.001; OS: 134.9 months vs 60.9 months; p = 0.003. Patients with stage III thymic carcinoma who received surgery had a longer OS than patients who did not receive surgery (70.1 months vs 23.9 months; p = 0.017, n = 11. Among 47 patients with stage IV carcinoma, 12 patients who received an extended thymothymectomy had a longer PFS than 35 patients who did not receive surgery (18.9 months vs 8.7 months; p = 0.029. Among 30 patients (with stage I- IV carcinoma who received primary lesion surgery, 19 patients received an R0 resection and 9 patients of the 19 patients received adjuvant radiotherapy. These patients had longer PFS (50.3 months than 2 patients who received adjuvant chemotherapy (5.9 months or 4 patients who received concurrent chemoradiotherapy (7.5 months after surgery (p = 0.003.Surgical resection should be considered for patients with thymic carcinoma, even for patients with locally advanced or stage IV carcinoma. Adjuvant radiotherapy resulted in a better PFS after R0 resection.

Assessment of the adjuvant activity of mesoporous silica nanoparticles in recombinant Mycoplasma hyopneumoniae antigen vaccines

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Veridiana Gomes Virginio

2017-01-01

Full Text Available The adjuvant potential of two mesoporous silica nanoparticles (MSNs, SBa-15 and SBa-16, was assessed in combination with a recombinant HSP70 surface polypeptide domain from Mycoplasma hyopneumoniae, the etiological agent of porcine enzootic pneumonia (PEP. The recombinant antigen (HSP70212-600, previously shown as immunogenic in formulation with classic adjuvants, was used to immunize BALB/c mice in combination with SBa-15 or SBa-16 MSNs, and the effects obtained with these formulations were compared to those obtained with alum, the adjuvant traditionally used in anti-PEP bacterins. The HSP70212-600 + SBa-15 vaccine elicited a strong humoral immune response, with high serum total IgG levels, comparable to those obtained using HSP70212-600 + alum. The HSP70212-600 + SBa-16 vaccine elicited a moderate humoral immune response, with lower levels of total IgG. The cellular immune response was assessed by the detection of IFN-γ, IL-4 and IL-10 in splenocyte culture supernatants. The HSP70212-600 + SBa-15 vaccine increased IFN-γ, IL-4 and IL-10 levels, while no stimulation was detected with the HSP70212-600 + SBa-16 vaccine. The HSP70212-600 + SBa-15 vaccine induced a mixed Th1/Th2-type response, with an additional IL-10 mediated anti-inflammatory effect, both of relevance for an anti-PEP vaccine. Alum adjuvant controls stimulated an unspecific cellular immune response, with similar levels of cytokines detected in mice immunized either with HSP70212-600 + alum or with the adjuvant alone. The better humoral and cellular immune responses elicited in mice indicated that SBa-15 has adjuvant potential, and can be considered as an alternative to the use of alum in veterinary vaccines. The use of SBa-15 with HSP70212-600 is also promising as a potential anti-PEP subunit vaccine formulation.

EVALUATION OF N-RATIO IN SELECTING PATIENTS FOR ADJUVANT CHEMORADIOTHERAPY AFTER D2-GASTRECTOMY

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Wilson Luiz da COSTA JUNIOR

2013-12-01

Full Text Available Context Whether adjuvant chemoradiotherapy may contribute to improve survival outcomes after D2-gastrectomy remains controvertial. Objective To explore the clinical utility of N-Ratio in selecting gastric cancer patients for adjuvant chemoradiotherapy after D2-gastrectomy. Methods A retrospective cohort study was carried out on gastric cancer patients who underwent D2-gastrectomy alone or D2-gastrectomy plus adjuvant chemoradiotherapy (INT-0116 protocol at the Hospital A. C. Camargo from September 1998 to December 2008. Statistical analysis were performed using multiple conventional methods, such as c-statistic, adjusted Cox's regression and stratified survival analysis. Results Our analysis involved 128 patients. According to c-statistic, the N-Ratio (i.e., as a continuous variable presented “area under ROC curve” (AUC of 0.713, while the number of metastatic nodes presented AUC of 0.705. After categorization, the cut-offs provide by Marchet et al. displayed the highest discriminating power – AUC value of 0.702. This N-Ratio categorization was confirmed as an independent predictor of survival using multivariate analyses. There also was a trend of better survival by adding of adjuvant chemoradiotherapy only for patients with milder degrees of lymphatic spread – 5-year survival of 23.1% vs 66.9%, respectively (HR = 0.426, 95% CI 0.150–1.202; P = 0.092. Conclusions This study confirms the N-Ratio as a tool to improve the lymph node metastasis staging in gastric cancer and suggests the cut-offs provided by Marchet et al. as the best way for its categorization after a D2-gastrectomy. In these settings, the N-Ratio appears a useful tool to select patients for adjuvant chemoradiotherapy, and the benefit of adding this type of adjuvancy to D2-gastrectomy is suggested to be limited to patients with milder degrees of lymphatic spread (i.e., NR2, 10%–25%.

The ethics of the medical-pharmaceutical relationship.

Science.gov (United States)

Vashi, Neelam A; Latkowski, Jo-Ann M

2012-01-01

Physician interaction with the pharmaceutical industry raises many ethical concerns. This relationship is complex, owing to a pluralism of beliefs held by physicians, patients, and third parties. As a result, determining whether physicians fulfill their responsibilities to both the professional and public communities is an arduous endeavor. In an effort to clarify the situation and provide transparency to this complex relationship, medical and pharmaceutical organizations have enacted their own respective codes and guidelines. Even with adherence to these guidelines, questions remain regarding the codependent relationship that interweaves the pharmaceutical industry with the medical community. Owing to the ever-changing landscape enmeshing product development, scientific advancement, corporate realities and patient care, the proper choice for physicians is rarely obvious; however, to operate to the highest standards, those in the medical community must be candid about relations with the pharmaceutical industry and transparent in their financial interests. Further undertakings should focus not on the eradication of physician-pharmaceutical interaction, but instead on the education of physicians about industry marketing strategies and the delineation of boundaries of these interactions to benefit not the individual physician, but our patients. Copyright © 2012. Published by Elsevier Inc.

Pharmaceutical care in smoking cessation

Directory of Open Access Journals (Sweden)

Marín Armero A

2015-01-01

Full Text Available Alicia Marín Armero,1 Miguel A Calleja Hernandez,2 Sabina Perez-Vicente,3 Fernando Martinez-Martinez4 1Community Pharmacy, Murcia, Spain; 2Hospital Pharmacy, University Hospital Virgen de las Nieves, Granada, Spain; 3Result Evaluation Unit, Institute of Biomedicine, Sevilla, Spain; 4Research Unit in Pharmaceutical Care, University of Granada, Granada, Spain Abstract: As a determining factor in various diseases and the leading known cause of preventable mortality and morbidity, tobacco use is the number one public health problem in developed countries. Facing this health problem requires authorities and health professionals to promote, via specific programs, health campaigns that improve patients’ access to smoking cessation services. Pharmaceutical care has a number of specific characteristics that enable the pharmacist, as a health professional, to play an active role in dealing with smoking and deliver positive smoking cessation interventions. The objectives of the study were to assess the efficacy of a smoking cessation campaign carried out at a pharmaceutical care center and to evaluate the effects of pharmaceutical care on patients who decide to try to stop smoking. The methodology was an open, analytical, pre–post intervention, quasi-experimental clinical study performed with one patient cohort. The results of the study were that the promotional campaign for the smoking cessation program increased the number of patients from one to 22, and after 12 months into the study, 43.48% of the total number of patients achieved total smoking cessation. We can conclude that advertising of a smoking cessation program in a pharmacy increases the number of patients who use the pharmacy’s smoking cessation services, and pharmaceutical care is an effective means of achieving smoking cessation. Keywords: community pharmacy, health campaign, tobacco cessation, nicotine replacement therapy

Synthetic biology advances for pharmaceutical production

OpenAIRE

Breitling, Rainer; Takano, Eriko

2015-01-01

Synthetic biology enables a new generation of microbial engineering for the biotechnological production of pharmaceuticals and other high-value chemicals. This review presents an overview of recent advances in the field, describing new computational and experimental tools for the discovery, optimization and production of bioactive molecules, and outlining progress towards the application of these tools to pharmaceutical production systems.

Inflammatory responses and side effects generated by several adjuvant-containing vaccines in turbot.

Science.gov (United States)

Noia, M; Domínguez, B; Leiro, J; Blanco-Méndez, J; Luzardo-Álvarez, A; Lamas, J

2014-05-01

Several of the adjuvants used in fish vaccines cause adhesions in internal organs when they are injected intraperitoneally. We describe the damage caused by vaccines containing different adjuvants in the turbot Scophthalmus maximus and show that internal adhesions can be greatly reduced by injecting the fish in a specific way. Injection of fish with the needle directed towards the anterior part of the peritoneal cavity induced formation of a single cell-vaccine mass (CVM) that became attached to the parietal peritoneum. However, injection of the fish with the needle pointing in the opposite direction generated many small CVM that became attached to the visceral and parietal peritoneum and in some cases caused internal adhesions. We describe the structural and cellular changes in the adjuvant-induced CVMs. The CVMs mainly comprised neutrophils and macrophages, although most of the former underwent apoptosis, which was particularly evident from day 3 post-injection. The apoptotic cells were phagocytosed by macrophages, which were the dominant cell type from the first days onwards. All of the vaccines induced angiogenesis in the area of contact between the CVM and the mesothelium. Vaccines containing oil-based adjuvants or microspheres induced the formation of granulomas in the CVM; however, no granulomas were observed in the CVM induced by vaccines containing aluminium hydroxide or Matrix-Q(®) as adjuvants. All of the vaccines induced strong migration of cells to the peritoneal cavity. Although some of these cells remained unattached in the peritoneal cavity, most of them formed part of the CVM. We also observed migration of the cells from the peritoneal cavity to lymphoid organs, indicating bidirectional traffic of cells between the inflamed areas and these organs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pricing and Reimbursement in U.S. Pharmaceutical Markets

OpenAIRE

Newhouse, Joseph Paul; Berndt, Ernst R.

2010-01-01

In this survey chapter on pricing and reimbursement in U.S. pharmaceutical markets, we first provide background information on important federal legislation, institutional details regarding distribution channel logistics, definitions of alternative price measures, related historical developments, and reasons why price discrimination is highly prevalent among branded pharmaceuticals. We then present a theoretical framework for the pricing of branded pharmaceuticals, without and then in the pre...

Assessing the assessments: Pharmaceuticals in the environment

International Nuclear Information System (INIS)

Enick, O.V.; Moore, M.M.

2007-01-01

The relatively new issue of pharmaceutical contamination of the environment offers the opportunity to explore the application of values to the construction, communication and management of risk. The still-developing regulatory policies regarding environmental contamination with pharmaceuticals provide fertile ground for the introduction of values into the definition and management of risk. In this report, we summarize the current knowledge regarding pharmaceutical contamination of the environment and discuss specific attributes of pharmaceuticals that require special consideration. We then present an analysis showing that if values are incorporated into assessing, characterizing and managing risk, the results of risk assessments will more accurately reflect the needs of various stakeholders. Originating from an acknowledgement of the inherent uncertainty and value-laden nature of risk assessment, the precautionary principle (and later, the multi-criteria, integrated risk assessment), provides a direction for further research and policy development

42 CFR 416.48 - Condition for coverage-Pharmaceutical services.

Science.gov (United States)

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Condition for coverage-Pharmaceutical services. 416... Coverage § 416.48 Condition for coverage—Pharmaceutical services. The ASC must provide drugs and... direction of an individual designated responsible for pharmaceutical services. (a) Standard: Administration...

Adjuvant radiotherapy for phyllodes tumor of the breast

International Nuclear Information System (INIS)

Chaney, Arthur W.; Pollack, Alan; Zagars, Gunar K.

1997-01-01

Purpose/Objective: The role of radiotherapy for the treatment of phyllodes tumors of the breast remains controversial. Adjuvant radiotherapy is often cited in the existing literature as not providing any benefit over surgical treatment alone. The data supporting this belief are anecdotal. There are also anecdotal reports that radiotherapy may have a role in cases wherein the risk of local failure is high. As with breast carcinomas, conservative surgery (wide local excision) for phyllodes tumors is associated with about a 50% local recurrence rate; diffuse or bulky disease and/or malignant histology are also associated with high local failure rates. We are unaware of any series that examines the role of adjuvant radiotherapy in the management of phyllodes tumor of the breast. We present here a retrospective study of eight patients so treated at MD Anderson Cancer Center. Materials and Methods: Eight patients have been treated with radiotherapy for non-metastatic phyllodes tumor of the breast at MD Anderson Cancer Center between December 1988 and August 1993. All patients were female; the median age was 43 years, with a range of 19 to 62 years. All patients presented with a breast mass, which was associated with pain in one patient, and was ulcerative in three. Results: Tumor size ranged from 3.5 to 16 cm, with a median diameter of 10.4 cm. Six patients had tumors in the upper outer quadrant, and two patients had upper inner tumors. Five patients had malignant tumors, two patients were classified as benign, and one was of indeterminate malignant potential. All five of the malignant tumors displayed stromal overgrowth on pathologic review. The remaining benign and indeterminate tumors lacked this feature. One patient with a benign tumor had a history of two prior recurrences. Primary surgery consisted of either lumpectomy in two patients or mastectomy in six patients. Axillary level I/II lymph node dissections were performed in 5 patients and no involvement was seen

Value of pharmaceuticals: ensuring the future of research and development.

Science.gov (United States)

Serajuddin, Hamida K; Serajuddin, Abu T M

2006-01-01

To analyze the current situation under which the pharmaceutical industry is criticized for the production of drugs with potential adverse effects, the high prices of medicines, and aggressive marketing practices, and to provide a proposal to rectify the situation. Published books, pharmaceutical journals, Web of Science database using the search terms pharmaceutical, research, development, marketing, cost, and the Food and Drug Administration (FDA) Web site. Most breakthroughs in the treatment of diseases and prolongation of lives have come about through pharmaceuticals discovered and developed by the pharmaceutical industry. While the process of discovering and developing new pharmaceuticals is lengthy, costly, and lacking any assurance of success, investment in research and development by the U.S. pharmaceutical industry has increased progressively, reaching 51.3 billion dollars in 2005. Yet the annual number of FDA approvals of new molecular entities (NMEs) has gradually decreased over the past 10 years. Additionally, a large part of the patent life of a successful NME is consumed during this lengthy development phase. Few businesses, if any, have such long product gestation lives and risks. For these reasons, the pharmaceutical industry is often in a rush to recoup its investment before the product's patent expires, and this is the root cause of many criticisms against the pharmaceutical industry. To rectify the current situation, a new system is proposed under which innovator pharmaceutical companies would be allowed royalties for their products after the expiration of patents, in a manner similar to the way in which other intellectual properties (such as books, music, films) are protected by copyright. Such a system would allow pharmaceutical companies to continue research on new pharmaceutical products unimpeded by the patent clock. Given appropriate legislative or other facilitatory actions, a royalty-based system for the marketing of generic products after

[The pharmaceutical industry in the industrial chemical group: the National Union of Chemical-Pharmaceutical Laboratories (1919-1936)].

Science.gov (United States)

Nozal, Raúl Rodríquez

2011-01-01

The pharmaceutical industry associations, as it happened with other businesses, had a significant rise during the dictatorship of Primo de Rivera and II Republic. The 'Cámara Nacional de Industrias Químicas', in Barcelona, represented the national chemical industry to its ultimate assimilation by the 'Organización Sindical' in 1939. In this association, matters relating to pharmaceutical products -- which we will especially deal with in this work -- were managed by the 'Unión Nacional de Laboratorios Químico-Farmacéuticos', which defended the interests of pharmaceutical companies in the presence of government authorities, using the resources and mechanisms also managed by business pressure groups. The inclusion of industrial pharmacy in the Chemical lobby separated the pharmaceutical industry from traditional exercise and its corporate environment. this created ups and downs, conflicts of interests and finally, love and hate relationships with their colleagues of the pharmacy work placement and, of course, with the association that represented them: the 'Unión Farmacéutica Nacional'.

Stage III Melanoma in the Axilla: Patterns of Regional Recurrence After Surgery With and Without Adjuvant Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Pinkham, Mark B., E-mail: mark.pinkham@health.qld.gov.au [Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane (Australia); University of Queensland, Brisbane (Australia); Foote, Matthew C. [Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane (Australia); Queensland Melanoma Project, Princess Alexandra Hospital, Brisbane (Australia); Diamantina Institute, Brisbane (Australia); University of Queensland, Brisbane (Australia); Burmeister, Elizabeth [Nursing Practice Development Unit, Princess Alexandra Hospital, Brisbane (Australia); Research Centre for Clinical and Community Practice, Griffith University, Brisbane (Australia); Thomas, Janine [Queensland Melanoma Project, Princess Alexandra Hospital, Brisbane (Australia); Meakin, Janelle [Clinical Trials Research Unit, Princess Alexandra Hospital, Brisbane (Australia); Smithers, B. Mark [Queensland Melanoma Project, Princess Alexandra Hospital, Brisbane (Australia); University of Queensland, Brisbane (Australia); Burmeister, Bryan H. [Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane (Australia); Queensland Melanoma Project, Princess Alexandra Hospital, Brisbane (Australia); University of Queensland, Brisbane (Australia)

2013-07-15

Purpose: To describe the anatomic distribution of regionally recurrent disease in patients with stage III melanoma in the axilla after curative-intent surgery with and without adjuvant radiation therapy. Methods and Materials: A single-institution, retrospective analysis of a prospective database of 277 patients undergoing curative-intent treatment for stage III melanoma in the axilla between 1992 and 2012 was completed. For patients who received radiation therapy and those who did not, patterns of regional recurrence were analyzed, and univariate analyses were performed to assess for potential factors associated with location of recurrence. Results: There were 121 patients who received adjuvant radiation therapy because their clinicopathologic features conferred a greater risk of regional recurrence. There were 156 patients who received no radiation therapy. The overall axillary control rate was 87%. There were 37 patients with regional recurrence; 17 patients had received adjuvant radiation therapy (14%), and 20 patients (13%) had not. The likelihood of in-field nodal recurrence was significantly less in the adjuvant radiation therapy group (P=.01) and significantly greater in sites adjacent to the axilla (P=.02). Patients with high-risk clinicopathologic features who did not receive adjuvant radiation therapy also tended to experience in-field failure rather than adjacent-field failure. Conclusions: Patients who received adjuvant radiation therapy were more likely to experience recurrence in the adjacent-field regions rather than in the in-field regions. This may not simply reflect higher-risk pathology. Using this data, it may be possible to improve outcomes by reducing the number of adjacent-field recurrences after adjuvant radiation therapy.

Efficacy of systemic adjuvant therapies administered to dogs after excision of oral malignant melanomas: 151 cases (2001-2012).

Science.gov (United States)

Boston, Sarah E; Lu, Xiaomin; Culp, William T N; Montinaro, Vincenzo; Romanelli, Giorgio; Dudley, Robert M; Liptak, Julius M; Mestrinho, Lisa A; Buracco, Paolo

2014-08-15

To determine prognostic factors for and compare outcome among dogs with oral malignant melanoma following excision with or without various systemic adjuvant therapies. Retrospective case series. 151 dogs with naturally occurring oral malignant melanomas treated by excision with or without adjuvant therapies from 2001 to 2012. Case accrual was solicited from Veterinary Society of Surgical Oncology members via an email list service. Information collected from case records included signalment, tumor staging, tumor characteristics, type of surgical excision, histologic diagnosis, adjuvant therapy, and survival time. The overall median survival time was 346 days. Results of multivariate analysis indicated that tumor size, patient age, and intralesional excision (vs marginal, wide, or radical excision) were considered poor prognostic indicators. All other demographic and clinical variables were not significantly associated with survival time after adjusting for the aforementioned 3 variables. A clear survival benefit was not evident with any systemic adjuvant therapy, including vaccination against melanoma or chemotherapy; however, the number of dogs in each treatment group was small. Ninety-eight dogs received no postoperative adjuvant therapy, and there was no difference in survival time between dogs that did (335 days) and did not (352 days) receive systemic adjuvant therapy. For dogs with oral malignant melanoma, increasing tumor size and age were negative prognostic factors. Complete excision of all macroscopic tumor burden improved survival time. Long-term survival was possible following surgery alone. Although systemic adjuvant therapy was not found to improve survival time, this could have been due to type II error.

Stage III Melanoma in the Axilla: Patterns of Regional Recurrence After Surgery With and Without Adjuvant Radiation Therapy

International Nuclear Information System (INIS)

Pinkham, Mark B.; Foote, Matthew C.; Burmeister, Elizabeth; Thomas, Janine; Meakin, Janelle; Smithers, B. Mark; Burmeister, Bryan H.

2013-01-01

Purpose: To describe the anatomic distribution of regionally recurrent disease in patients with stage III melanoma in the axilla after curative-intent surgery with and without adjuvant radiation therapy. Methods and Materials: A single-institution, retrospective analysis of a prospective database of 277 patients undergoing curative-intent treatment for stage III melanoma in the axilla between 1992 and 2012 was completed. For patients who received radiation therapy and those who did not, patterns of regional recurrence were analyzed, and univariate analyses were performed to assess for potential factors associated with location of recurrence. Results: There were 121 patients who received adjuvant radiation therapy because their clinicopathologic features conferred a greater risk of regional recurrence. There were 156 patients who received no radiation therapy. The overall axillary control rate was 87%. There were 37 patients with regional recurrence; 17 patients had received adjuvant radiation therapy (14%), and 20 patients (13%) had not. The likelihood of in-field nodal recurrence was significantly less in the adjuvant radiation therapy group (P=.01) and significantly greater in sites adjacent to the axilla (P=.02). Patients with high-risk clinicopathologic features who did not receive adjuvant radiation therapy also tended to experience in-field failure rather than adjacent-field failure. Conclusions: Patients who received adjuvant radiation therapy were more likely to experience recurrence in the adjacent-field regions rather than in the in-field regions. This may not simply reflect higher-risk pathology. Using this data, it may be possible to improve outcomes by reducing the number of adjacent-field recurrences after adjuvant radiation therapy

Curcumin potentiates the anti-arthritic effect of prednisolone in Freund's complete adjuvant-induced arthritic rats.

Science.gov (United States)

Kuncha, Madhusudana; Naidu, Vegi Ganga Modi; Sahu, Bidya Dhar; Gadepalli, Shankar Ganesh; Sistla, Ramakrishna

2014-01-01

The present study was aimed at investigating the effect of curcumin in combination with prednisolone for the effective treatment of arthritis with reduced side effects when glucocorticoids therapy is indicated. Arthritis was induced in wistar rats by subplantar injection of Freund's complete adjuvant, and animals were observed for the symptoms of arthritis during the period of 21 days. Combined treatment of curcumin with various doses of prednisolone (1.25, 2.5 and 5 mg/kg) was evaluated in order to ascertain the efficacy and toxicity induced by steroid. Arthritic animals showed significant increase in tumour necrosis factor-α and IL-1β levels in paw tissue and IL-1β in serum. Combined therapy of curcumin with low doses of prednisolone showed pronounced beneficial effect on joint swelling, leucocyte count and biochemical parameters compared with prednisolone groups. Among the different doses used in the study, prednisolone at 1.25 mg/kg in combination with curcumin showed beneficial anti-arthritic activity and also reduced the steroid toxicity. This is evidenced by increase in body weight, low toxicity to immune organs, reduction in leucocyte count, increase in spleen anti-oxidant enzymes and potent inhibition of cytokines in combination group. Therefore, combined treatment of curcumin with low doses of prednisolone may find therapeutic use in arthritis. © 2013 Royal Pharmaceutical Society.

Case histories in pharmaceutical risk management.

Science.gov (United States)

McCormick, Cynthia G; Henningfield, Jack E; Haddox, J David; Varughese, Sajan; Lindholm, Anders; Rosen, Susan; Wissel, Janne; Waxman, Deborah; Carter, Lawrence P; Seeger, Vickie; Johnson, Rolley E

2009-12-01

The development and implementation of programs in the U.S. to minimize risks and assess unintended consequences of new medications has been increasingly required by the Food and Drug Administration (FDA) since the mid 1990s. This paper provides four case histories of risk management and post-marketing surveillance programs utilized recently to address problems associated with possible abuse, dependence and diversion. The pharmaceutical sponsors of each of these drugs were invited to present their programs and followed a similar template for their summaries that are included in this article. The drugs and presenting companies were OxyContin, an analgesic marketed by Purdue Pharma L.P., Daytrana and Vyvanse, ADHD medications marketed by Shire Pharmaceuticals, Xyrem for narcolepsy marketed by Jazz Pharmaceuticals, and Subutex and Suboxone for opioid dependence marketed by Reckitt Benckiser Pharmaceuticals Inc. These case histories and subsequent discussions provide invaluable real-world examples and illustrate both the promise of risk management programs in providing a path to market and/or for keeping on the market drugs with serious potential risks. They also illustrate the limitations of such programs in actually controlling unintended consequences, as well as the challenge of finding the right balance of reducing risks without posing undue barriers to patient access. These experiences are highly relevant as the FDA increasingly requires pharmaceutical sponsors to develop and implement the more formalized and enforceable versions of the risk management term Risk Evaluation and Mitigation Strategies (REMS).

Pharmaceutical care in smoking cessation.

Science.gov (United States)

Marín Armero, Alicia; Calleja Hernandez, Miguel A; Perez-Vicente, Sabina; Martinez-Martinez, Fernando

2015-01-01

As a determining factor in various diseases and the leading known cause of preventable mortality and morbidity, tobacco use is the number one public health problem in developed countries. Facing this health problem requires authorities and health professionals to promote, via specific programs, health campaigns that improve patients' access to smoking cessation services. Pharmaceutical care has a number of specific characteristics that enable the pharmacist, as a health professional, to play an active role in dealing with smoking and deliver positive smoking cessation interventions. The objectives of the study were to assess the efficacy of a smoking cessation campaign carried out at a pharmaceutical care center and to evaluate the effects of pharmaceutical care on patients who decide to try to stop smoking. The methodology was an open, analytical, pre-post intervention, quasi-experimental clinical study performed with one patient cohort. The results of the study were that the promotional campaign for the smoking cessation program increased the number of patients from one to 22, and after 12 months into the study, 43.48% of the total number of patients achieved total smoking cessation. We can conclude that advertising of a smoking cessation program in a pharmacy increases the number of patients who use the pharmacy's smoking cessation services, and pharmaceutical care is an effective means of achieving smoking cessation.

[Written pharmaceutical advertising--still unreliable?].

Science.gov (United States)

Gladsø, Kristin Haugen; Garberg, Hedda Rosland; Spigset, Olav; Slørdal, Lars

2014-09-02

Marketing by the pharmaceutical industry affects doctors' prescribing habits. All pharmaceutical advertising received by nine doctors in two GP offices over a period of three months was collected. The advertising material was sorted by compound. For each compound, the advert with the highest number of references was selected. The cited references were obtained, and the claims in the adverts were assessed in terms of their consistency with the source data based on the provisions in the Norwegian regulations on pharmaceuticals. The references were also assessed with regard to the incidence of conflicts of interest among authors. The doctors received a total of 270 shipments of advertising for 46 different compounds. Altogether 95% of the 173 references cited in the 46 selected adverts could be obtained. The adverts contained a total of 156 claims. Of these, 56% were assessed as correct when compared to the source data and as having clinical relevance. Altogether 75% of the journal articles reported relevant conflicts of interest for the authors. About half the claims in the adverts were found to be correct and clinically relevant. These results concur with those from a methodologically identical study based on advertising material collected in 2004. The cited literature was of varying quality and often funded by the pharmaceutical companies. The findings indicate that the target group should be sceptical of this type of marketing.

Cost-containment as part of pharmaceutical policy

DEFF Research Database (Denmark)

Almarsdóttir, Anna Birna; Traulsen, Janine Marie

2005-01-01

and profit controls; 2) reimbursement system charges; 3) other fiscal measures; 4) quality measures. Pharmaceuticals policy has suffered from the pervasive misunderstanding that drugs are like any other commodity; resulting in policy makers viewing pharmaceuticals expenditures without thinking about drugs...

Information sources and utilization patterns of pharmaceutical ...

African Journals Online (AJOL)

The study investigated the adequacy of pharmaceutical scientists' information environment in feeding their occupational activities. Data was collected through observation and through questionnaire administration to all the twenty-seven scientists in two large pharmaceutical companies in Lagos, Nigeria. Findings revealed ...

Pharmaceutical penetration of new drug and pharmaceutical market structure in Taiwan: hospital-level prescription of thiazolidinediones for diabetes.

Science.gov (United States)

Tsai, Yi-Wen; Wen, Yu-Wen; Huang, Weng-Foung; Kuo, Ken N; Chen, Pei-Fen; Shih, Hsin-Wei; Lee, Yue-Chune

2010-06-01

This study used Taiwan's National Health Insurance claim database (years 2000-2005) to examine how thiazolidinediones (TZD), a new class of drugs for diabetes, penetrated into Taiwan's hospitals, and its association with the concentration of all diabetes drugs at the hospital level. We collected 72 monthly summaries of diabetes prescriptions from all hospitals in Taiwan. Hospital-level pharmaceutical concentration was measured by penetration of TZD, defined as monthly market share of TZD in each hospital. Concentration of diabetes drugs was measured by Herfindahl-Hirschman indices. We found a negative association (coefficient = -0.3610) between TZD penetration and concentration of diabetes drug but a positive association between penetration of TZD and the volume of prescribed diabetes drugs (coefficient = 0.4088). In conclusion, hospital characteristics and volume of services determined the concentration of pharmaceuticals at the institution level, reflecting the heterogeneous competition between pharmaceutical companies within each hospital. Institution-level pharmaceutical concentration influences the adoption and penetration of new drugs.

Rational Use of Medicines in Relation to Pharmaceutical Supply ...

African Journals Online (AJOL)

Pharmaceutical management involves a set of practices aiming at ensuring timely availability and appropriate use of safe, effective and quality pharmaceuticals and services in any health care setting. Rational use of medicines is often associated with efficiency of pharmaceutical supply system that operates in the health ...

Human Phase 1 trial of low-dose inactivated seasonal influenza vaccine formulated with Advax™ delta inulin adjuvant.

Science.gov (United States)

Gordon, David L; Sajkov, Dimitar; Honda-Okubo, Yoshikazu; Wilks, Samuel H; Aban, Malet; Barr, Ian G; Petrovsky, Nikolai

2016-07-19

Influenza vaccines are usually non-adjuvanted but addition of adjuvant may improve immunogenicity and permit dose-sparing, critical for vaccine supply in the event of an influenza pandemic. The aim of this first-in-man study was to determine the effect of delta inulin adjuvant on the safety and immunogenicity of a reduced dose seasonal influenza vaccine. Healthy male and female adults aged 18-65years were recruited to participate in a randomized controlled study to compare the safety, tolerability and immunogenicity of a reduced-dose 2007 Southern Hemisphere trivalent inactivated influenza vaccine formulated with Advax™ delta inulin adjuvant (LTIV+Adj) when compared to a full-dose of the standard TIV vaccine which does not contain an adjuvant. LTIV+Adj provided equivalent immunogenicity to standard TIV vaccine as assessed by hemagglutination inhibition (HI) assays against each vaccine strain as well as against a number of heterosubtypic strains. HI responses were sustained at 3months post-immunisation in both groups. Antibody landscapes against a large panel of H3N2 influenza viruses showed distinct age effects whereby subjects over 40years old had a bimodal baseline HI distribution pattern, with the highest HI titers against the very oldest H3N2 isolates and with a second HI peak against influenza isolates from the last 5-10years. By contrast, subjects >40years had a unimodal baseline HI distribution with peak recognition of H3N2 isolates from approximately 20years ago. The reduced dose TIV vaccine containing Advax adjuvant was well tolerated and no safety issues were identified. Hence, delta inulin may be a useful adjuvant for use in seasonal or pandemic influenza vaccines. Australia New Zealand Clinical Trial Registry: ACTRN12607000599471. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adjuvant chemotherapy for stage I non-seminomatous testicular ...

African Journals Online (AJOL)

Adjuvant chemotherapy for stage I non-seminomatous testicular cancer. R. P. Abratt, A. R. Pontin, R. D. Barnes, B. V. Reddi. Developments in the treatment of stage I ... taxing for patients.·. Analysis of tumour histology in the orchidectomy specimen in patients entered into surveillance studies led to the identification of risk ...

Membrane Bioprocesses for Pharmaceutical Micropollutant Removal from Waters

Directory of Open Access Journals (Sweden)

Matthias de Cazes

2014-10-01

Full Text Available The purpose of this review work is to give an overview of the research reported on bioprocesses for the treatment of domestic or industrial wastewaters (WW containing pharmaceuticals. Conventional WW treatment technologies are not efficient enough to completely remove all pharmaceuticals from water. Indeed, these compounds are becoming an actual public health problem, because they are more and more present in underground and even in potable waters. Different types of bioprocesses are described in this work: from classical activated sludge systems, which allow the depletion of pharmaceuticals by bio-degradation and adsorption, to enzymatic reactions, which are more focused on the treatment of WW containing a relatively high content of pharmaceuticals and less organic carbon pollution than classical WW. Different aspects concerning the advantages of membrane bioreactors for pharmaceuticals removal are discussed, as well as the more recent studies on enzymatic membrane reactors to the depletion of these recalcitrant compounds.

Prioritizing veterinary pharmaceuticals for aquatic environment in Korea.

Science.gov (United States)

Kim, Younghee; Jung, Jinyong; Kim, Myunghyun; Park, Jeongim; Boxall, Alistair B A; Choi, Kyungho

2008-09-01

Pharmaceutical residues may have serious impacts on nontarget biological organisms in aquatic ecosystems, and have therefore precipitated numerous investigations worldwide. Many pharmaceutical compounds available on the market need to be prioritized based on their potential ecological and human health risks in order to develop sound management decisions. We prioritized veterinary pharmaceuticals in Korea by their usage, potential to enter the environment, and toxicological hazard. Twenty compounds were identified in the top priority class, most of which were antibiotics. Among these compounds, 8 were identified as deserving more immediate attention: amoxicillin, enramycin, fenbendazole, florfenicol, ivermectin, oxytetracycline, tylosin, and virginiamycin. A limitation of this study is that we initially screened veterinary pharmaceuticals by sales tonnage for veterinary use only. However, this is the first attempt to prioritize veterinary pharmaceuticals in Korea, and it provides important concepts for developing environmental risk management plans for such contaminants in aquatic systems. Copyright © 2008 Elsevier B.V. All rights reserved.

Ozonation for degradation of pharmaceutical in hospital wastewater

DEFF Research Database (Denmark)

Bester, Kai; Hansen, Kamilla S; Spiliotopoulou, Aikaterini

-pollutants (Antoniou et al., 2013). In the present work, ozonation of biological treated hospital wastewater spiked with pharmaceuticals were performed to determine the required ozone dose for 90 % removal of the investigated pharmaceuticals. Effluents with different DOC level were used to investigate the effect...... of DOC on the removal of the pharmaceuticals. Furthermore, the effect of pH on ozone decomposition was investigated in relevant pH range....

The behaviour of pharmaceuticals in anaerobic digester sludge

OpenAIRE

Campbell, Alison

2013-01-01

Pharmaceuticals are biologically active compounds that may be consumed in hundreds of tonnes per year, and which are excreted into municipal sewerage systems. Many pharmaceuticals persist during sewage treatment, and significant environmental risk has been linked to incomplete removal of pharmaceuticals. Evaluation of this risk is important and should be as representative as possible, taking into consideration all significant exposure routes and removal processes. Sludge treatment processes a...

Adjuvant chemo-radiation for gastric adenocarcinoma: an institutional experience

International Nuclear Information System (INIS)

Aftimos, Philippe G; Nasr, Elie A; Nasr, Dolly I; Noun, Roger J; Nasr, Fady L; Ghosn, Marwan G; El Helou, Joelle A; Chahine, Georges Y

2010-01-01

Studies have shown that surgery alone is less than satisfactory in the management of early gastric cancer, with cure rates approaching 40%. The role of adjuvant therapy was indefinite until three large, randomized controlled trials showed the survival benefit of adjuvant therapy over surgery alone. Chemoradiation therapy has been criticized for its high toxicity. 24 patients diagnosed between September 2001 and July 2007 were treated with adjuvant chemoradiation. 18 patients had the classical MacDonald regimen of 4500 cGy of XRT and chemotherapy with 5-fluorouracil (5FU) and leucovorin, while chemotherapy consisted of 5FU/Cisplatin for 6 patients. This series consisted of non-metastatic patients, 17 females and 7 males with a median age of 62.5 years. 23 patients (96%) had a performance status of 0 or 1. The full course of radiation therapy (4500 cGy) was completed by 22 patients (91.7%). Only 7 patients (36.8%) completed the total planned courses of chemotherapy. 2 local relapses (10%), 2 regional relapses (10%) and 2 distant relapses (10%) were recorded. Time to progression has not been reached. 9 patients (37.5%) died during follow-up with a median overall survival of 75 months. Patients lost a mean of 4 Kgs during radiation therapy. We recorded 6 episodes of febrile neutropenia and the most frequent toxicity was gastro-intestinal in 17 patients (70.8%) with 9 (36%) patients suffering grade 3 or 4 toxicity and 5 patients (20%) suffering from grade 3 or 4 neutropenia. 4 (17%) patients required total parenteral nutrition for a mean duration of 20 days. 4 patients suffered septic shock (17%) and 1 patient developed a deep venous thrombosis and a pulmonary embolus. Adjuvant chemo-radiation for gastric cancer is a standard at our institution and has resulted in few relapses and an interesting median survival. Toxicity rates were serious and this remains a harsh regimen with only 36.8% of patients completing the full planned courses of chemotherapy. This is due to

Adjuvant chemo-radiation for gastric adenocarcinoma: an institutional experience

Directory of Open Access Journals (Sweden)

Ghosn Marwan G

2010-06-01

Full Text Available Abstract Background Studies have shown that surgery alone is less than satisfactory in the management of early gastric cancer, with cure rates approaching 40%. The role of adjuvant therapy was indefinite until three large, randomized controlled trials showed the survival benefit of adjuvant therapy over surgery alone. Chemoradiation therapy has been criticized for its high toxicity. Methods 24 patients diagnosed between September 2001 and July 2007 were treated with adjuvant chemoradiation. 18 patients had the classical MacDonald regimen of 4500 cGy of XRT and chemotherapy with 5-fluorouracil (5FU and leucovorin, while chemotherapy consisted of 5FU/Cisplatin for 6 patients. Results This series consisted of non-metastatic patients, 17 females and 7 males with a median age of 62.5 years. 23 patients (96% had a performance status of 0 or 1. The full course of radiation therapy (4500 cGy was completed by 22 patients (91.7%. Only 7 patients (36.8% completed the total planned courses of chemotherapy. 2 local relapses (10%, 2 regional relapses (10% and 2 distant relapses (10% were recorded. Time to progression has not been reached. 9 patients (37.5% died during follow-up with a median overall survival of 75 months. Patients lost a mean of 4 Kgs during radiation therapy. We recorded 6 episodes of febrile neutropenia and the most frequent toxicity was gastro-intestinal in 17 patients (70.8% with 9 (36% patients suffering grade 3 or 4 toxicity and 5 patients (20% suffering from grade 3 or 4 neutropenia. 4 (17% patients required total parenteral nutrition for a mean duration of 20 days. 4 patients suffered septic shock (17% and 1 patient developed a deep venous thrombosis and a pulmonary embolus. Conclusions Adjuvant chemo-radiation for gastric cancer is a standard at our institution and has resulted in few relapses and an interesting median survival. Toxicity rates were serious and this remains a harsh regimen with only 36.8% of patients completing the

Occurrence, sources, and fate of pharmaceuticals in aquatic environment and soil

International Nuclear Information System (INIS)

Li, W.C.

2014-01-01

With the rapid economic development, a better living condition leads to longer life expectancy, which increased the total population, in particular the elderly group. It may result in increase in the demand of pharmaceuticals for people in domestic use or in hospital. Although most sewage treatment plants or waste water treatment plantsmet the regulatory requirement, there are still many pharmaceuticals removed incompletely and thus discharged to the environment. Therefore, the pharmaceuticals residue draws the public concern because they might cause adverse effects on the organism even human beings. Recently, many studies have published on the source and occurrence as well as the fate of pharmaceuticals all over the world. This paper summarized and reviewed the recent studies on the sources, occurrence, fate and the effects of the most common pharmaceuticals. Finally, it gave the suggestion and risk management for controlling the pharmaceuticals. - Highlights: • The sources of pharmaceutical residuals are studied. • Occurrence and fate of pharmaceutical in environment are studied. • Risk management and recommendation are provided on pharmaceutical pollution. - Concentration of pharmaceuticals in the natural environment is lower than in effluent of sewage treatment plants in which carbamazepine is found frequently in soil and water body

Synthetic biology advances for pharmaceutical production

Science.gov (United States)

Breitling, Rainer; Takano, Eriko

2015-01-01

Synthetic biology enables a new generation of microbial engineering for the biotechnological production of pharmaceuticals and other high-value chemicals. This review presents an overview of recent advances in the field, describing new computational and experimental tools for the discovery, optimization and production of bioactive molecules, and outlining progress towards the application of these tools to pharmaceutical production systems. PMID:25744872

Microbial Evaluation of Some Non-sterile Pharmaceutical ...

African Journals Online (AJOL)

Purpose: To determine the type and incidence of predominant microorganisms in certain non-sterile pharmaceuticals immediately after collection and one year later. Methods: All pharmaceutical samples were subjected to the following examinations: total bacterial count and presence of microbial pathogens, using ...

Review on Physicochemical, Chemical, and Biological Processes for Pharmaceutical Wastewater

Science.gov (United States)

Li, Zhenchen; Yang, Ping

2018-02-01

Due to the needs of human life and health, pharmaceutical industry has made great progress in recent years, but it has also brought about severe environmental problems. The presence of pharmaceuticals in natural waters which might pose potential harm to the ecosystems and humans raised increasing concern worldwide. Pharmaceuticals cannot be effectively removed by conventional wastewater treatment plants (WWTPs) owing to the complex composition, high concentration of organic contaminants, high salinity and biological toxicity of pharmaceutical wastewater. Therefore, the development of efficient methods is needed to improve the removal effect of pharmaceuticals. This review provides an overview on three types of treatment technologies including physicochemical, chemical and biological processes and their advantages and disadvantages respectively. In addition, the future perspectives of pharmaceutical wastewater treatment are given.

Information flow in the pharmaceutical supply chain.

Science.gov (United States)

Yousefi, Nazila; Alibabaei, Ahmad

2015-01-01

Managing the supply chain plays an important role in creating competitive advantages for companies. Adequate information flow in supply chain is one of the most important issues in SCM. Therefore, using certain Information Systems can have a significant role in managing and integrating data and information within the supply chain. Pharmaceutical supply chain is more complex than many other supply chains, in the sense that it can affect social and political perspectives. On the other hand, managing the pharmaceutical supply chain is difficult because of its complexity and also government regulations in this field. Although, Iran has progressed a lot in pharmaceutical manufacturing, still there are many unsolved issues in managing the information flow in the pharmaceutical supply chain. In this study, we reviewed the benefits of using different levels of an integrated information system in the supply chain and the possible challenges ahead.

Pharmaceutical marketing research and the prescribing physician.

Science.gov (United States)

Greene, Jeremy A

2007-05-15

Surveillance of physicians' prescribing patterns and the accumulation and sale of these data for pharmaceutical marketing are currently the subjects of legislation in several states and action by state and national medical associations. Contrary to common perception, the growth of the health care information organization industry has not been limited to the past decade but has been building slowly over the past 50 years, beginning in the 1940s when growth in the prescription drug market fueled industry interest in understanding and influencing prescribing patterns. The development of this surveillance system was not simply imposed on the medical profession by the pharmaceutical industry but was developed through the interactions of pharmaceutical salesmen, pharmaceutical marketers, academic researchers, individual physicians, and physician organizations. Examination of the role of physicians and physician organizations in the development of prescriber profiling is directly relevant to the contemporary policy debate surrounding this issue.

Funding pharmaceutical innovation through direct tax credits.

Science.gov (United States)

Lybecker, Kristina M; Freeman, Robert A

2007-07-01

Rising pharmaceutical prices, increasing demand for more effective innovative drugs and growing public outrage have heightened criticism of the pharmaceutical industry. The public debate has focused on drug prices and access. As a consequence, the patent system is being reexamined as an efficient mechanism for encouraging pharmaceutical innovation and drug development. We propose an alternative to the existing patent system, instead rewarding the innovating firm with direct tax credits in exchange for marginal cost pricing. This concept is based on the fundamental assumption that innovation that benefits society at large may be financed publicly. As an industry which produces a social good characterized by high fixed costs, high information and regulatory costs, and relatively low marginal costs of production, pharmaceuticals are well-suited to such a mechanism. Under this proposal, drug prices fall, consumer surplus increases, access is enhanced, and the incentives to innovate are preserved.

Microbiological testing of pharmaceuticals and cosmetics in Egypt.

Science.gov (United States)

Zeitoun, Hend; Kassem, Mervat; Raafat, Dina; AbouShlieb, Hamida; Fanaki, Nourhan

2015-12-09

Microbial contamination of pharmaceuticals poses a great problem to the pharmaceutical manufacturing process, especially from a medical as well as an economic point of view. Depending upon the product and its intended use, the identification of isolates should not merely be limited to the United States Pharmacopeia (USP) indicator organisms. Eighty-five pre-used non-sterile pharmaceuticals collected from random consumers in Egypt were examined for the eventual presence of bacterial contaminants. Forty-one bacterial contaminants were isolated from 31 of the tested preparations. These isolates were subjected to biochemical identification by both conventional tests as well as API kits, which were sufficient for the accurate identification of only 11 out of the 41 bacterial contaminants (26.8%) to the species level. The remaining isolates were inconclusively identified or showed contradictory results after using both biochemical methods. Using molecular methods, 24 isolates (58.5%) were successfully identified to the species level. Moreover, polymerase chain reaction (PCR) assays were compared to standard biochemical methods in the detection of pharmacopoeial bacterial indicators in artificially-contaminated pharmaceutical samples. PCR-based methods proved to be superior regarding speed, cost-effectiveness and sensitivity. Therefore, pharmaceutical manufacturers would be advised to adopt PCR-based methods in the microbiological quality testing of pharmaceuticals in the future.

[Pharmaceutical product quality control and good manufacturing practices].

Science.gov (United States)

Hiyama, Yukio

2010-01-01

This report describes the roles of Good Manufacturing Practices (GMP) in pharmaceutical product quality control. There are three keys to pharmaceutical product quality control. They are specifications, thorough product characterization during development, and adherence to GMP as the ICH Q6A guideline on specifications provides the most important principles in its background section. Impacts of the revised Pharmaceutical Affairs Law (rPAL) which became effective in 2005 on product quality control are discussed. Progress of ICH discussion for Pharmaceutical Development (Q8), Quality Risk Management (Q9) and Pharmaceutical Quality System (Q10) are reviewed. In order to reconstruct GMP guidelines and GMP inspection system in the regulatory agencies under the new paradigm by rPAL and the ICH, a series of Health Science studies were conducted. For GMP guidelines, product GMP guideline, technology transfer guideline, laboratory control guideline and change control system guideline were written. For the GMP inspection system, inspection check list, inspection memo and inspection scenario were proposed also by the Health Science study groups. Because pharmaceutical products and their raw materials are manufactured and distributed internationally, collaborations with other national authorities are highly desired. In order to enhance the international collaborations, consistent establishment of GMP inspection quality system throughout Japan will be essential.

Adjuvant chemo radiation in gastric cancer Hospital Dr. R. A. Calderon Guardia

International Nuclear Information System (INIS)

Badilla Gonzalez, Ronald

2006-01-01

This work establishes the associated factors to the early recurrence of gastric cancer in the patients who have received adjuvant chemoradiation in the Hospital Dr. R. A. Calderon Guardia. It was determined if the personal factors such as age and gender influence in the evolution of theses cases. The importance of characteristics of the tumour as T, N, location, Borrmann type and histological type in the evolution of the disease was estimated, too. It mentions the epidemiological characteristics of patients who have received the therapy and describes the toxicity of the treatment. A retrospective-descriptive method was utilized and the clinical records of the patients of the hospital with gastric cancer diagnosis were reviewed. These patients were surgery candidates and then they received adjuvant ia with chemoradiation from 2003 and with at lest 12 months of monitoring. The main conclusions are: Hospital Calderon Guardia practices the surgery with D2 ganglionar dissection as treatment of potentially curable gastric cancer. The population with gastric cancer has a predominance of men and people between seventh and fifth decade of life. The studied series had a recurrent tendency for female sex. To major pT (pathologic size) of the tumour there is more risks of recurrence. The pattern of regional recurrence in peritoneal carcinomathosis shape is which has a tendency to predominate after the adjuvant treatment in gastric cancer. The toxicity of the adjuvant treatment for gastric cancer is not severe and it is manageable without necessity of suspend the treatment in the majority of the cases [es

Global risk of pharmaceutical contamination from highly populated developing countries.

Science.gov (United States)

Rehman, Muhammad Saif Ur; Rashid, Naim; Ashfaq, Muhammad; Saif, Ameena; Ahmad, Nasir; Han, Jong-In

2015-11-01

Global pharmaceutical industry has relocated from the west to Asian countries to ensure competitive advantage. This industrial relocation has posed serious threats to the environment. The present study was carried out to assess the possible pharmaceutical contamination in the environment of emerging pharmaceutical manufacturing countries (Bangladesh, China, India and Pakistan). Although these countries have made tremendous progress in the pharmaceutical sector but most of their industrial units discharge wastewater into domestic sewage network without any treatment. The application of untreated wastewater (industrial and domestic) and biosolids (sewage sludge and manure) in agriculture causes the contamination of surface water, soil, groundwater, and the entire food web with pharmaceutical compounds (PCs), their metabolites and transformed products (TPs), and multidrug resistant microbes. This pharmaceutical contamination in Asian countries poses global risks via product export and international traveling. Several prospective research hypotheses including the development of new analytical methods to monitor these PCs/TPs and their metabolites, highly resistant microbial strains, and mixture toxicity as a consequence of pharmaceutical contamination in these emerging pharmaceutical exporters have also been proposed based on the available literature. Copyright © 2013 Elsevier Ltd. All rights reserved.

Efficacy of Killed Adjuvanted FMD Vaccine Developed with ...

African Journals Online (AJOL)

In this study the potency of killed Foot and Mouth Disease (FMD) vaccines serotypes SAT1 (Nig 1/98) and SAT 2 (Nig 2/97) virus isolates, formulated with montanide ISA 206 adjuvant was determined in guinea pigs and cattle by antibody assay using Complement Fixation and Serum Neutralization tests. The antibody titres ...

Microbiological testing of pharmaceuticals and cosmetics in Egypt

OpenAIRE

Zeitoun, Hend; Kassem, Mervat; Raafat, Dina; AbouShlieb, Hamida; Fanaki, Nourhan

2015-01-01

Background Microbial contamination of pharmaceuticals poses a great problem to the pharmaceutical manufacturing process, especially from a medical as well as an economic point of view. Depending upon the product and its intended use, the identification of isolates should not merely be limited to the United States Pharmacopeia (USP) indicator organisms. Results Eighty-five pre-used non-sterile pharmaceuticals collected from random consumers in Egypt were examined for the eventual presence of b...

FACTORS AFFECTING EMPLOYEE JOB SATISFACTION OF PHARMACEUTICAL SECTOR

OpenAIRE

Mosammod Mahamuda Parvin; M M Nurul Kabir

2011-01-01

The Pharmaceutical sector plays a vital role in underpinning the economic development of a country. This study attempts to evaluate job satisfaction of employees in different pharmaceutical companies. It focuses on the relative importance of job satisfaction factors and their impacts on the overall job satisfaction of employees. It also investigates the impacts of pharmaceutical type, work experience, age, and sex differences on the attitudes toward job Satisfaction. The result shows that sal...

Adjuvant Radiation Therapy Treatment Time Impacts Overall Survival in Gastric Cancer

International Nuclear Information System (INIS)

McMillan, Matthew T.; Ojerholm, Eric; Roses, Robert E.; Plastaras, John P.; Metz, James M.; Mamtani, Ronac; Karakousis, Giorgos C.; Fraker, Douglas L.; Drebin, Jeffrey A.; Stripp, Diana; Ben-Josef, Edgar; Datta, Jashodeep

2015-01-01

Purpose: Prolonged radiation therapy treatment time (RTT) is associated with worse survival in several tumor types. This study investigated whether delays during adjuvant radiation therapy impact overall survival (OS) in gastric cancer. Methods and Materials: The National Cancer Data Base was queried for patients with resected gastric cancer who received adjuvant radiation therapy with National Comprehensive Cancer Network–recommended doses (45 or 50.4 Gy) between 1998 and 2006. RTT was classified as standard (45 Gy: 33-36 days, 50.4 Gy: 38-41 days) or prolonged (45 Gy: >36 days, 50.4 Gy: >41 days). Cox proportional hazards models evaluated the association between the following factors and OS: RTT, interval from surgery to radiation therapy initiation, interval from surgery to radiation therapy completion, radiation therapy dose, demographic/pathologic and operative factors, and other elements of adjuvant multimodality therapy. Results: Of 1591 patients, RTT was delayed in 732 (46%). Factors associated with prolonged RTT were non-private health insurance (OR 1.3, P=.005) and treatment at non-academic facilities (OR 1.2, P=.045). Median OS and 5-year actuarial survival were significantly worse in patients with prolonged RTT compared with standard RTT (36 vs 51 months, P=.001; 39 vs 47%, P=.005); OS worsened with each cumulative week of delay (P<.0004). On multivariable analysis, prolonged RTT was associated with inferior OS (hazard ratio 1.2, P=.002); the intervals from surgery to radiation therapy initiation or completion were not. Prolonged RTT was particularly detrimental in patients with node positivity, inadequate nodal staging (<15 nodes examined), and those undergoing a cycle of chemotherapy before chemoradiation therapy. Conclusions: Delays during adjuvant radiation therapy appear to negatively impact survival in gastric cancer. Efforts to minimize cumulative interruptions to <7 days should be considered

Adjuvant endocrine therapy for premenopausal women with hormone-responsive breast cancer.

Science.gov (United States)

Mathew, Aju; Davidson, Nancy E

2015-11-01

Multiple strategies for endocrine treatment of premenopausal women with hormone-responsive breast cancer have been assessed and results have been presented over the last two years. These include tamoxifen for 5-10 years (ATLAS and aTTom), tamoxifen for 5 years followed by aromatase inhibitor (AI) for 5 years for women who have become postmenopausal (MA-17); ovarian ablation (OA) by surgery (EBCTCG overview); ovarian function suppression (OFS) by LHRH agonist (LHRH agonist meta-analysis); or combinations of approaches including OFS plus tamoxifen or AI (SOFT, TEXT, ABCSG 12 and E3193). Many of these trials have taken place in the backdrop of (neo)adjuvant chemotherapy which can confound interpretation because such therapy can suppress ovarian function either transiently or permanently. Nonetheless these trials suggest in aggregate that 10 years of tamoxifen are better than 5 years and that a program of extended adjuvant therapy of tamoxifen for 5 years followed by aromatase inhibitor for 5 years is effective for suitable candidates. The SOFT and E3193 trials do not show a major advantage for use of OFS + tamoxifen compared to tamoxifen alone. The joint SOFT/TEXT analysis and ABCGS12 trials both suggest that outcomes can be excellent with the use of combined endocrine therapy alone in properly selected patients but give conflicting results with regard to potential benefits for OFS + AI compared with OFS + tamoxifen. Further work will be needed to ascertain long-term outcomes, identify factors that predict who will benefit from extended adjuvant endocrine therapy, and assess role of OFS by medical or surgical means. It is clear, however, that endocrine therapy is a critical part of the adjuvant regimen for most premenopausal women with hormone-responsive breast cancer, and a subset of these women with luminal A-type tumors can be safely treated with endocrine therapy alone. Copyright © 2015 Elsevier Ltd. All rights reserved.

Adjuvant Radiation Therapy Treatment Time Impacts Overall Survival in Gastric Cancer

Energy Technology Data Exchange (ETDEWEB)

McMillan, Matthew T. [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Ojerholm, Eric [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Roses, Robert E., E-mail: Robert.Roses@uphs.upenn.edu [Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Plastaras, John P.; Metz, James M. [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Mamtani, Ronac [Department of Hematology/Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Karakousis, Giorgos C.; Fraker, Douglas L.; Drebin, Jeffrey A. [Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Stripp, Diana; Ben-Josef, Edgar [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Datta, Jashodeep [Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States)

2015-10-01

Purpose: Prolonged radiation therapy treatment time (RTT) is associated with worse survival in several tumor types. This study investigated whether delays during adjuvant radiation therapy impact overall survival (OS) in gastric cancer. Methods and Materials: The National Cancer Data Base was queried for patients with resected gastric cancer who received adjuvant radiation therapy with National Comprehensive Cancer Network–recommended doses (45 or 50.4 Gy) between 1998 and 2006. RTT was classified as standard (45 Gy: 33-36 days, 50.4 Gy: 38-41 days) or prolonged (45 Gy: >36 days, 50.4 Gy: >41 days). Cox proportional hazards models evaluated the association between the following factors and OS: RTT, interval from surgery to radiation therapy initiation, interval from surgery to radiation therapy completion, radiation therapy dose, demographic/pathologic and operative factors, and other elements of adjuvant multimodality therapy. Results: Of 1591 patients, RTT was delayed in 732 (46%). Factors associated with prolonged RTT were non-private health insurance (OR 1.3, P=.005) and treatment at non-academic facilities (OR 1.2, P=.045). Median OS and 5-year actuarial survival were significantly worse in patients with prolonged RTT compared with standard RTT (36 vs 51 months, P=.001; 39 vs 47%, P=.005); OS worsened with each cumulative week of delay (P<.0004). On multivariable analysis, prolonged RTT was associated with inferior OS (hazard ratio 1.2, P=.002); the intervals from surgery to radiation therapy initiation or completion were not. Prolonged RTT was particularly detrimental in patients with node positivity, inadequate nodal staging (<15 nodes examined), and those undergoing a cycle of chemotherapy before chemoradiation therapy. Conclusions: Delays during adjuvant radiation therapy appear to negatively impact survival in gastric cancer. Efforts to minimize cumulative interruptions to <7 days should be considered.

Application of “Systems Vaccinology” to Evaluate Inflammation and Reactogenicity of Adjuvanted Preventative Vaccines

Directory of Open Access Journals (Sweden)

David J. M. Lewis

2015-01-01

Full Text Available Advances in “omics” technology (transcriptomics, proteomics, metabolomics, genomics/epigenomics, etc. allied with statistical and bioinformatics tools are providing insights into basic mechanisms of vaccine and adjuvant efficacy or inflammation/reactogenicity. Predictive biomarkers of relatively frequent inflammatory reactogenicity may be identified in systems vaccinology studies involving tens or hundreds of participants and used to screen new vaccines and adjuvants in in vitro, ex vivo, animal, or human models. The identification of rare events (such as those observed with initial rotavirus vaccine or suspected autoimmune complications will require interrogation of large data sets and population-based research before application of systems vaccinology. The Innovative Medicine Initiative funded public-private project BIOVACSAFE is an initial attempt to systematically identify biomarkers of relatively common inflammatory events after adjuvanted immunization using human, animal, and population-based models. Discriminatory profiles or biomarkers are being identified, which require validation in large trials involving thousands of participants before they can be generalized. Ultimately, it is to be hoped that the knowledge gained from such initiatives will provide tools to the industry, academia, and regulators to select optimal noninflammatory but immunogenic and effective vaccine adjuvant combinations, thereby shortening product development cycles and identifying unsuitable vaccine candidates that would fail in expensive late stage development or postmarketing.

Metrology in Pharmaceutical Industry - A Case Study

International Nuclear Information System (INIS)

Yuvamoto, Priscila D.; Fermam, Ricardo K. S.; Nascimento, Elizabeth S.

2016-01-01

Metrology is recognized by improving production process, increasing the productivity, giving more reliability to the measurements and consequently, it impacts in the economy of a country. Pharmaceutical area developed GMP (Good Manufacture Practice) requeriments, with no introduction of metrological concepts. However, due to Nanomedicines, it is expected this approach and the consequent positive results. The aim of this work is to verify the level of metrology implementation in a Brazilian pharmaceutical industry, using a case study. The purpose is a better mutual comprehension by both areas, acting together and governmental support to robustness of Brazilian pharmaceutical area. (paper)

Pharmaceuticals as indictors of sewage-influenced groundwater

Science.gov (United States)

Müller, Beate; Scheytt, Traugott; Asbrand, Martin; de Casas, Andrea Mross

2012-09-01

A set of human pharmaceuticals enables identification of groundwater that is influenced by sewage and provides information on the time of recharge. As the consumption rates of the investigated pharmaceuticals have changed over time, so too has the composition of the sewage. At the study area, south of Berlin (Germany), irrigation was performed as a method of wastewater clean-up at sewage irrigation farms until the early 1990s. Today, treated wastewater is discharged into the surface-water-stream Nuthegraben. Groundwater and surface-water samples were analyzed for the pharmaceutical substances clofibric acid, bezafibrate, diclofenac, carbamazepine and primidone, the main ions and organic carbon. The pharmaceutical substances were detected at concentrations up to microgram-per-liter level in groundwater and surface-water samples from the Nuthegraben Lowland area and from the former irrigation farms. Concentrations detected in groundwater are generally much lower than in surface water and there is significant variation in the distribution of pharmaceutical concentrations in groundwater. Groundwater influenced by the irrigation of sewage water shows higher primidone and clofibric-acid concentrations. Groundwater influenced by recent discharge of treated sewage water into the surface water shows high carbamazepine concentrations while concentrations of primidone and clofibric acid are low.

Tropical Journal of Pharmaceutical Research: About this journal

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Tropical Journal of Pharmaceutical Research: About this journal. Journal Home > Tropical Journal of Pharmaceutical Research: About this journal. Log in or Register to get access to full text downloads.

Nigerian Journal of Pharmaceutical Research: About this journal

African Journals Online (AJOL)

Nigerian Journal of Pharmaceutical Research: About this journal. Journal Home > Nigerian Journal of Pharmaceutical Research: About this journal. Log in or Register to get access to full text downloads.

Cell-Based Veterinary Pharmaceuticals – Basic Legal Parameters Set by the Veterinary Pharmaceutical Law and the Genetic Engineering Law of the European Union

Science.gov (United States)

Faltus, Timo; Brehm, Walter

2016-01-01

Cell-based therapies have been in use in veterinary medicine for years. However, the legal requirement of manufacturing, placing on the market and use of cell-based veterinary pharmaceuticals are not as well developed as the respective requirements of chemical pharmaceuticals. Cell-based veterinary pharmaceuticals are medicinal products in the sense of the pharmaceutical law of the European Union (EU). For that reason, such medicinal products principally require official approval for their manufacture and an official marketing authorization for their placement on the market before being used by the veterinarian. The manufacture, placing on the market, and use of cell-based veterinary pharmaceuticals without manufacturing approval and marketing authorization is permitted only in certain exceptional cases determined by EU and individual Member State law. Violations of this requirement may have consequences for the respective veterinarian under criminal law and under the code of professional conduct in the respective Member State. The regular use of cell-based veterinary pharmaceuticals within the scope of a therapeutic emergency as well as the import of such veterinary pharmaceuticals from non-European countries for use in the EU are currently out of the question in the EU because of a lack of legal bases. Here, we review the general legal requirement of manufacturing, placing on the market, and use of cell-based veterinary pharmaceuticals within the EU and point out different implementations of EU law within the different Member States. PMID:27965965

Pharmacoligaclly Active: Clinical Trials and the Pharmaceuticals ...

African Journals Online (AJOL)

Multinational pharmaceutical companies ('pharmas') import and produce pharmaceuticals and also conduct clinical trials which are an important aspect of research and development (R&D). This may raise the question: Is South Africa a guinea pig for the pharmas? The Department of Trade and Industry National Industrial ...

Pharmaceutical crystallography: is there a devil in the details?

DEFF Research Database (Denmark)

Bond, A. D.

2012-01-01

Modern instruments for small-molecule crystallography continue to become more sophisticated and more automated. This technical progress provides a basis for frontier research in chemical and pharmaceutical crystallography, but it also encourages analytical crystallographers to become more...... are presented for pharmaceutical compounds, and the potential importance of the "details" in pharmaceutical crystallography is discussed....

Effects of soil properties on the uptake of pharmaceuticals into earthworms

International Nuclear Information System (INIS)

Carter, Laura J.; Ryan, Jim J.; Boxall, Alistair B.A.

2016-01-01

Pharmaceuticals can enter the soil environment when animal slurries and sewage sludge are applied to land as a fertiliser or during irrigation with contaminated water. These pharmaceuticals may then be taken up by soil organisms possibly resulting in toxic effects and/or exposure of organisms higher up the food chain. This study investigated the influence of soil properties on the uptake and depuration of pharmaceuticals (carbamazepine, diclofenac, fluoxetine and orlistat) in the earthworm Eisenia fetida. The uptake and accumulation of pharmaceuticals into E. fetida changed depending on soil type. Orlistat exhibited the highest pore water based bioconcentration factors (BCFs) and displayed the largest differences between soil types with BCFs ranging between 30.5 and 115.9. For carbamazepine, diclofenac and fluoxetine BCFs ranged between 1.1 and 1.6, 7.0 and 69.6 and 14.1 and 20.4 respectively. Additional analysis demonstrated that in certain treatments the presence of these chemicals in the soil matrices changed the soil pH over time, with a statistically significant pH difference to control samples. The internal pH of E. fetida also changed as a result of incubation in pharmaceutically spiked soil, in comparison to the control earthworms. These results demonstrate that a combination of soil properties and pharmaceutical physico-chemical properties are important in terms of predicting pharmaceutical uptake in terrestrial systems and that pharmaceuticals can modify soil and internal earthworm chemistry which may hold wider implications for risk assessment. - Highlights: • Uptake of pharmaceuticals into earthworms is influenced by soil parameters. • Presence of pharmaceuticals in the terrestrial environment influences soil pH. • Uptake of pharmaceuticals by earthworms changes internal earthworm pH. - The uptake of pharmaceuticals into soil invertebrates is dependent on the complex interplay between pharmaceutical physico-chemical properties and soil

Pharmaceutical care: the PCNE definition 2013.

Science.gov (United States)

Allemann, Samuel S; van Mil, J W Foppe; Botermann, Lea; Berger, Karin; Griese, Nina; Hersberger, Kurt E

2014-06-01

Twenty-three years after Hepler and Strand published their well-known definition of Pharmaceutical Care (PhC), confusion remains about what the term includes and how to differentiate it from other terms. The board of the Pharmaceutical Care Network Europe (PCNE) felt the need to redefine PhC and to answer the question: "What is Pharmaceutical Care in 2013". The aims of this paper were to review existing definitions of PhC and to describe the process of developing a redefined definition. A literature search was conducted in the MEDLINE database (1964-January 2013). Keywords included "Pharmaceutical Care", "Medication (Therapy) Management", "Medicine Management", and "Pharmacist Care" in the title or abstract together with the term "defin*". To ease comparison between definitions, we developed a standardised syntax to paraphrase the definitions. During a dedicated meeting, a moderated discussion about the definition of PhC was organised. The initial literature search produced 186 hits, with eight unique PhC definitions. Hand searching identified a further 11 unique definitions. These 19 definitions were paraphrased using the standardised syntax (provider, recipient, subject, outcome, activities). Fourteen members of PCNE and 10 additional experts attended the moderated discussion. Working groups of increasing size developed intermediate definitions, which had similarities and differences to those retrieved in the literature search. At the end of the session, participants reached a consensus on a "PCNE definition of Pharmaceutical Care" reading: "Pharmaceutical Care is the pharmacist's contribution to the care of individuals in order to optimize medicines use and improve health outcomes". It was possible to paraphrase definitions of PhC using a standardised syntax focusing on the provider, recipient, subject, outcomes, and activities included in PhC practice. During a one-day workshop, experts in PhC research agreed on a definition, intended to be applicable for the

Mergers and innovation in the pharmaceutical industry.

Science.gov (United States)

Comanor, William S; Scherer, F M

2013-01-01

Conflicting trends confound the pharmaceutical industry. The productivity of pharmaceutical innovation has declined in recent years. At the same time, the cohort of large companies who are the leading engines of pharmaceutical R&D has become increasingly concentrated. The concurrent presence of these trends is not sufficient to determine causation. In response to lagging innovation prospects, some companies have sought refuge in mergers and acquisitions to disguise their dwindling prospects or gain R&D synergies. On the other hand, the increased concentration brought on by recent mergers may have contributed to the declining rate of innovation. In this paper, we consider the second of these causal relationships: the likely impact of the recent merger wave among the largest pharmaceutical companies on the rate of innovation. In other words, have recent mergers, which may have been taken in response to lagging innovation, represented a self-defeating strategy that only made industry outcomes worse? Copyright © 2012 Elsevier B.V. All rights reserved.

Financing pharmaceuticals in transition economies.

Science.gov (United States)

Kanavos, P

1999-06-01

This paper (a) provides a methodological taxonomy of pricing, financing, reimbursement, and cost containment methodologies for pharmaceuticals; (b) analyzes complex agency relationships and the health versus industrial policy tradeoff; (c) pinpoints financing measures to balance safety and effectiveness of medicines and their affordability by publicly funded systems in transition; and (d) highlights viable options for policy-makers for the financing of pharmaceuticals in transition. Three categories of measures and their implications for pharmaceutical policy cost containing are analyzed: supply-side measures, targeting manufacturers, proxy demand-side measures, targeting physicians and pharmacists, and demand-side measures, targeting patients. In pursuing supply side measures, we explore free pricing for pharmaceuticals, direct price controls, cost-plus and cost pricing, average pricing and international price comparisons, profit control, reference pricing, the introduction of a fourth hurdle, positive and negative lists, and other price control measures. The analysis of proxy-demand measures includes budgets for physicians, generic policies, practice guidelines, monitoring the authorizing behavior of physicians, and disease management schemes. Demand-side measures explore the effectiveness of patient co-payments, the impact of allowing products over-the-counter and health promotion programs. Global policies should operate simultaneously on the supply, the proxy demand, and the demand-side. Policy-making needs to have a continuous long-term planning. The importation of policies into transition economy may require extensive and expensive adaptation, and/or lead to sub-optimal policy outcomes.

New perspectives for visual characterization of pharmaceutical solids

DEFF Research Database (Denmark)

Laitinen, Niklas; Antikainen, Osmo; Rantanen, Jukka

2004-01-01

The utilization of descriptive image information in pharmaceutical powder technology is rather limited. Consequently, the development of this discipline is a challenge within physical characterization of pharmaceutical solids. The aim of this study was to develop and evaluate an inventive visual...... in particle size analysis also enabling the evaluation of the further product quality in the end of the granulation process. The idea of characterization of bulk surface images opens new perspectives for characterization of pharmaceutical solids....

Physical Therapy Adjuvants to Promote Optimization of Walking Recovery after Stroke

Directory of Open Access Journals (Sweden)

Mark G. Bowden

2011-01-01

Full Text Available Stroke commonly results in substantial and persistent deficits in locomotor function. The majority of scientific inquiries have focused on singular intervention approaches, with recent attention given to task specific therapies. We propose that measurement should indicate the most critical limiting factor(s to be addressed and that a combination of adjuvant treatments individualized to target accompanying impairment(s will result in the greatest improvements in locomotor function. We explore training to improve walking performance by addressing a combination of: (1 walking specific motor control; (2 dynamic balance; (3 cardiorespiratory fitness and (4 muscle strength and put forward a theoretical framework to maximize the functional benefits of these strategies as physical adjuvants. The extent to which any of these impairments contribute to locomotor dysfunction is dependent on the individual and will undoubtedly change throughout the rehabilitation intervention. Thus, the ability to identify and measure the relative contributions of these elements will allow for identification of a primary intervention as well as prescription of additional adjuvant approaches. Importantly, we highlight the need for future studies as appropriate dosing of each of these elements is contingent on improving the capacity to measure each element and to titrate the contribution of each to optimal walking performance.

Freund's vaccine adjuvant promotes Her2/Neu breast cancer

International Nuclear Information System (INIS)

Cotroneo, Michelle S; Haag, Jill D; Stapel, Nicholas R; Waller, Jordy L; Woditschka, Stephan; Gould, Michael N

2009-01-01

Inflammation has been linked to the etiology of many organ-specific cancers. Indirect evidence suggests a possible role for inflammation in breast cancer. We investigated whether the systemic inflammation induced by Freund's adjuvant (FA) promotes mammary carcinogenesis in a rat model in which cancer is induced by the neu oncogene. The effects of FA on hyperplastic mammary lesions and mammary carcinomas were determined in a neu-induced rat model. The inflammatory response to FA treatment was gauged by measuring acute phase serum haptoglobin. In addition, changes in cell proliferation and apoptosis following FA treatment were assessed. Rats receiving FA developed twice the number of mammary carcinomas as controls. Systemic inflammation following FA treatment is chronic, as shown by a doubling of the levels of the serum biomarker, haptoglobin, 15 days following initial treatment. We also show that this systemic inflammation is associated with the increased growth of hyperplastic mammary lesions. This increased growth results from a higher rate of cellular proliferation in the absence of changes in apoptosis. Our data suggests that systemic inflammation induced by Freund's adjuvant (FA) promotes mammary carcinogenesis. It will be important to determine whether adjuvants currently used in human vaccines also promote breast cancer

Assessing the Factors Associated With Iran's Intra-Industry Trade in Pharmaceuticals.

Science.gov (United States)

Yusefzadeh, Hassan; Hadian, Mohammad; Abolghasem Gorji, Hassan; Ghaderi, Hossein

2015-03-30

Pharmaceutical industry is a sensitive and profitable industry. If this industry wants to survive, it should be able to compete well in international markets. So, study of Iran's intra-industry trade (IIT) in pharmaceuticals is essential in order to identify competitiveness potential of country and boost export capability in the global arena. This study assessed the factors associated with Iran's intra-industry trade in pharmaceuticals with the rest of the world during the 2001-2012 periods using seasonal time series data at the four-digit SITC level. The data was collected from Iran's pharmaceutical Statistics, World Bank and International Trade Center. Finally, we discussed a number of important policy recommendations to increase Iran's IIT in pharmaceuticals. The findings indicated that economies of scale, market structure and degree of economic development had a significantly positive impact on Iran's intra-industry trade in pharmaceuticals and tariff trade barriers were negatively related to IIT. Product differentiation and technological advancement didn't have the expected signs. In addition, we found that Iran's IIT in pharmaceuticals have shown an increasing trend during the study period. Thus, the composition of Iran trade in pharmaceuticals has changed from inter-industry trade to intra-industry trade. In order to get more prepared for integration into the global economy, the development of Iran's IIT in pharmaceuticals should be given priority. Therefore, paying attention to IIT could have an important role in serving pharmaceutical companies in relation to pharmaceutical trade.

On radiation treatment of pharmaceutical products

International Nuclear Information System (INIS)

Zukov, V.; Mende, V.

1976-01-01

The progress made in the GDR over the past decade in the field of radiosterilization of products of the medical industry, has naturally raised the question of radiosterilization in pharmaceutics. However, because of the diversity and complicated nature of pharmaceutical products and, consequently, longer periods of time required for preliminary studies, their radiosterilization has not yet been applied on an industrial scale, in contrast to the situation in the medical industry. The studies carried out so far have been mainly concerned with ascertaining the permissibility and effectiveness of radiosterilization of individual products under particular conditions rather than with laying down a broad theoretical basis. Accordingly, the present paper does not describe results of special studies but presents a brief rewiev of some studies on radiation treatment of pharmaceutical products undertaken in the GDR. (author)

Pharmaceutical cocrystals, salts and polymorphs: Advanced characterization techniques.

Science.gov (United States)

Pindelska, Edyta; Sokal, Agnieszka; Kolodziejski, Waclaw

2017-08-01

The main goal of a novel drug development is to obtain it with optimal physiochemical, pharmaceutical and biological properties. Pharmaceutical companies and scientists modify active pharmaceutical ingredients (APIs), which often are cocrystals, salts or carefully selected polymorphs, to improve the properties of a parent drug. To find the best form of a drug, various advanced characterization methods should be used. In this review, we have described such analytical methods, dedicated to solid drug forms. Thus, diffraction, spectroscopic, thermal and also pharmaceutical characterization methods are discussed. They all are necessary to study a solid API in its intrinsic complexity from bulk down to the molecular level, gain information on its structure, properties, purity and possible transformations, and make the characterization efficient, comprehensive and complete. Furthermore, these methods can be used to monitor and investigate physical processes, involved in the drug development, in situ and in real time. The main aim of this paper is to gather information on the current advancements in the analytical methods and highlight their pharmaceutical relevance. Copyright © 2017 Elsevier B.V. All rights reserved.

Approaches to education of pharmaceutical biotechnology in faculties of pharmacy.

Science.gov (United States)

Calis, S; Oner, F; Kas, S; Hincal, A A

2001-06-01

Pharmaceutical biotechnology is developing rapidly both in academic institutions and in the biopharmaceutical industry. For this reason, FIP Special Interest Group of Pharmaceutical Biotechnology decided to develop a questionnaire concerning pharmaceutical biotechnology education. After preliminary studies were completed, questionnaires were sent to the leading scientists in academia and research directors or senior managers of various Pharmaceutical Biotechnology Companies in order to gather their views about how to create a satisfactory program. The objectives of this study were as follows: -To review all of the graduate and undergraduate courses which are presently available worldwide on pharmaceutical biotechnology in Faculties of Pharmacy. -To review all of the text books, references and scientific sources available worldwide in the area of pharmaceutical biotechnology. When replying to the questionnaires, the respondents were asked to consider the present status of pharmaceutical biotechnology education in academia and future learning needs in collaboration with the biotechnology industry. The data from various pharmacy faculties and biotechnology industry representatives from Asia, Europe and America were evaluated and the outcome of the survey showed that educational efforts in training qualified staff in the rapidly growing field of pharmaceutical biotechnology is promising. Part of the results of this questionnaire study have already been presented at the 57th International Congress of FIP Vancouver, Canada in 1997.

Antibody and Cytokine Responses of Koalas (Phascolarctos cinereus) Vaccinated with Recombinant Chlamydial Major Outer Membrane Protein (MOMP) with Two Different Adjuvants.

Science.gov (United States)

Khan, Shahneaz Ali; Desclozeaux, Marion; Waugh, Courtney; Hanger, Jon; Loader, Jo; Gerdts, Volker; Potter, Andrew; Polkinghorne, Adam; Beagley, Kenneth; Timms, Peter

2016-01-01

Developing a vaccine against Chlamydia is key to combating widespread mortalities and morbidities associated with this infection in koalas (Phascolarctos cinereus). In previous studies, we have shown that two or three doses of a Recombinant Major Outer Membrane Protein (rMOMP) antigen-based vaccine, combined with immune stimulating complex (ISC) adjuvant, results in strong cellular and humoral immune responses in koalas. We have also separately evaluated a single dose vaccine, utilising a tri-adjuvant formula that comprises polyphosphazine based poly I: C and host defense peptides, with the same antigen. This formulation also produced strong cellular and humoral immune responses in captive koalas. In this current study, we directly compared the host immune responses of two sub-groups of wild Chlamydia negative koalas in one population vaccinated with the rMOMP protein antigen and adjuvanted with either the ISC or tri-adjuvant formula. Overall, both adjuvants produced strong Chlamydia-specific cellular (IFN-γ and IL-17A) responses in circulating PBMCs as well as MOMP-specific and functional, in vitro neutralising antibodies. While the immune responses were similar, there were adjuvant-specific immune differences between the two adjuvants, particularly in relation to the specificity of the MOMP epitope antibody responses.

Antibody and Cytokine Responses of Koalas (Phascolarctos cinereus Vaccinated with Recombinant Chlamydial Major Outer Membrane Protein (MOMP with Two Different Adjuvants.

Directory of Open Access Journals (Sweden)

Shahneaz Ali Khan

Full Text Available Developing a vaccine against Chlamydia is key to combating widespread mortalities and morbidities associated with this infection in koalas (Phascolarctos cinereus. In previous studies, we have shown that two or three doses of a Recombinant Major Outer Membrane Protein (rMOMP antigen-based vaccine, combined with immune stimulating complex (ISC adjuvant, results in strong cellular and humoral immune responses in koalas. We have also separately evaluated a single dose vaccine, utilising a tri-adjuvant formula that comprises polyphosphazine based poly I: C and host defense peptides, with the same antigen. This formulation also produced strong cellular and humoral immune responses in captive koalas. In this current study, we directly compared the host immune responses of two sub-groups of wild Chlamydia negative koalas in one population vaccinated with the rMOMP protein antigen and adjuvanted with either the ISC or tri-adjuvant formula. Overall, both adjuvants produced strong Chlamydia-specific cellular (IFN-γ and IL-17A responses in circulating PBMCs as well as MOMP-specific and functional, in vitro neutralising antibodies. While the immune responses were similar, there were adjuvant-specific immune differences between the two adjuvants, particularly in relation to the specificity of the MOMP epitope antibody responses.

The pharmaceutical quality revolution

Directory of Open Access Journals (Sweden)

Jordi Botet

2016-01-01

Full Text Available Pharmaceutical products are patient-oriented. If they had a deficient quality they might put live at risk. Ensuring their quality is not, however, a straightforward task and this is why different approaches have been used along the way. This article analyzes them and shows how our present approach, if well implemented, is very effective in ensuring quality.Methods. This article analyzes the current pharmaceutical quality system as described by international guidances in the light of practical experience gathered by the author as an international GMP-consultant.Result. Nowadays we have come to understand that as quality is a global concept in terms of time and of requirements, it has to be assured in a global way too. This is why quality assurance is a permanent process that starts during the development of a product and goes on during its manufacturing life. Manufacturing should be performed within a pharmaceutical quality system which ensures GMP compliance. Decisions should be science and risk-based. Products and processes are monitored by means of critical variables.Conclusions. The approach followed in the 21st century for ensuring quality is very effective and allows for a progressive reduction of the level of quality risk. However, this quality system is either comprehensive or there is no quality

21 CFR 172.710 - Adjuvants for pesticide use dilutions.

Science.gov (United States)

2010-04-01

... Section 172.710 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Other Specific Usage Additives § 172.710 Adjuvants for pesticide use dilutions. The...

Postoperative adjuvant chemotherapy in rectal cancer operated for cure

DEFF Research Database (Denmark)

Petersen, Sune Høirup; Harling, Henrik; Kirkeby, Lene Tschemerinsky

2012-01-01

Colorectal cancer is one of the most common types of cancer in the Western world. Apart from surgery - which remains the mainstay of treatment for resectable primary tumours - postoperative (i.e., adjuvant) chemotherapy with 5-fluorouracil (5-FU) based regimens is now the standard treatment in Du...

A randomised controlled trial comparing the effect of adjuvant ...

African Journals Online (AJOL)

Background: Intrathecal adjuvants are added to local anaesthetics to improve the quality of neuraxial blockade and prolong the duration of analgesia during spinal anaesthesia. Used intrathecally, fentanyl improves the quality of spinal blockade as compared to plain bupivacaine and confers a short duration of post ...

Adjuvant activity of peanut, cottonseed and rice oils on cellular and humoral response

Directory of Open Access Journals (Sweden)

Erika Freitas

2013-04-01

Full Text Available The potentiality of the usage of vegetable oils such as soybean, corn, olive, sesame, murici seed, rapeseed, linseed, rice and cashew nuts as adjuvant of the humoral and cellular immune response has been recently shown. In the present work, besides of evaluating the adjuvant action of peanut, cottonseed and rice oils on humoral and cellular immune responses against ovalbumin (OVA we also evaluated the protective immune response induced by Leishmania antigens. The peanut oil significantly increased the synthesis of anti-ovalbumin antibodies in the primary response, but it did not favor cellular response. Concerning mice immunized with L. amazonensis antigens emulsified with peanut oil exacerbated skin lesions and lymph node parasite load what suggests stimulation of the Th2 immune response and down regulation of Th1 response. The cottonseed oil was shown to have adjuvant effect to the humoral response, stimulating a secondary response and also favored the delayed-type hypersensitivity (DTH response to OVA. The rice oil stimulated a strong DTH reaction to OVA and enhanced the synthesis of antibodies after the third dose. Mice immunized with L. amazonensis antigens emulsified with rice oil or cotton seed oil were protected from developing skin lesions and lymph node parasite load. These results emphasize the interest and importance of the vegetable oils as tools in different procedures of immunization and their differential role in relation to the other adjuvant under usage.

[Resected non-small cell bronchogenic carcinoma stage pIIIA-N2. Which patients will benefit most from adjuvant therapy?].

Science.gov (United States)

Gómez, Ana M; Jarabo, José Ramón; Fernandez, Cristina; Calatayud, Joaquín; Fernández, Elena; Torres, Antonio J; Balibrea, José L; Hernando, Florentino

2014-04-01

Controversy persists as regards the indications and results of surgery in the treatment of patients with stage pIIIA-N2 non-small cell lung cancer (NSCLC). The objective of this study was to analyze the overall survival of a multicentre series of these patients and the role of adjuvant treatment, looking for factors that may define subgroups of patients with an increased benefit from this treatment. A retrospective study was conducted on 287 patients, with stage pIIIA-N2 NSCLC subjected to complete resection, taken from a multi-institutional database of 2.994 prospectively collected consecutive patients who underwent surgery for lung cancer. Adjuvant treatment was administered in 238 cases (82.9%). Analyses were made of the age, gender, histological type, administration of induction and adjuvant chemotherapy and/or radiation therapy treatments. The 5-year survival was 24%, with a median survival of 22 months. Survival was 26.5% among patients receiving with adjuvant treatment, versus 10.7% for those without it (P=.069). Age modified the effect of adjuvant treatment on survival (interaction P=.049). In patients under 70 years of age with squamous cell carcinoma, adjuvant treatment reduced the mortality rate by 37% (hazard ratio: 0,63; 95% CI; 0,42-0,95; P=.036). Completely resected patients with stage pIIIA-N2 NSCLC receiving adjuvant treatment reached higher survival rates than those who did not. Maximum benefit was achieved by the subgroup of patients under 70 years of age with squamous cell carcinoma. Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.

RFID in the pharmaceutical industry: addressing counterfeits with technology.

Science.gov (United States)

Taylor, Douglas

2014-11-01

The use of Radio Frequency Identification (RFID) in the pharmaceutical industry has grown in recent years. The technology has matured from its specialized tracking and retail uses to a systemic part of supply chain management in international pharmaceutical production and distribution. Counterfeit drugs, however, remain a significant challenge for governments, pharmaceutical companies, clinicians, and patients and the use of RFID to track these compounds represents an opportunity for development. This paper discusses the medical, technological, and economic factors that support widespread adoption of RFID technology in the pharmaceutical industry in an effort to prevent counterfeit medicines from harming patients and brand equity.

Compliance with adjuvant treatment guidelines in endometrial cancer: room for improvement in high risk patients.

Science.gov (United States)

Eggink, F A; Mom, C H; Boll, D; Ezendam, N P M; Kruitwagen, R F P M; Pijnenborg, J M A; van der Aa, M A; Nijman, H W

2017-08-01

Compliance of physicians with guidelines has emerged as an important indicator for quality of care. We evaluated compliance of physicians with adjuvant therapy guidelines for endometrial cancer patients in the Netherlands in a population-based cohort over a period of 10years. Data from all patients diagnosed with endometrial cancer between 2005 and 2014, without residual tumor after surgical treatment, were extracted from the Netherlands Cancer Registry (N=14,564). FIGO stage, grade, tumor type and age were used to stratify patients into risk groups. Possible changes in compliance over time and impact of compliance on survival were assessed. Patients were stratified into low/low-intermediate (52%), high-intermediate (21%) and high (20%) risk groups. Overall compliance with adjuvant therapy guidelines was 85%. Compliance was highest in patients with low/low-intermediate risk (98%, no adjuvant therapy indicated). The lowest compliance was determined in patients with high risk (61%, external beam radiotherapy with/without chemotherapy indicated). Within this group compliance decreased from 64% in 2005-2009 to 57% in 2010-2014. In high risk patients with FIGO stage III serous disease compliance was 55% (chemotherapy with/without radiotherapy indicated) and increased from 41% in 2005-2009 to 66% in 2010-2014. While compliance of physicians with adjuvant therapy guidelines is excellent in patients with low and low-intermediate risk, there is room for improvement in high risk endometrial cancer patients. Eagerly awaited results of ongoing randomized clinical trials may provide more definitive guidance regarding adjuvant therapy for high risk endometrial cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

influence of manufacturing practices on quality of pharmaceutical

African Journals Online (AJOL)

hi-tech

2004-06-01

Jun 1, 2004 ... PHARMACEUTICAL PRODUCTS MANUFACTURED IN KENYA. J. A. ORWA, L. K. ... Design: Cross-sectional study. ... of good manufacturing practices has been used in the production of each pharmaceutical product by ...

Adjuvant Radiation Therapy and Survival for Pure Tubular Breast Carcinoma-Experience From the SEER Database

Energy Technology Data Exchange (ETDEWEB)

Li Baoqing, E-mail: bal9018@med.cornell.edu [Department of Radiation Oncology, Weill Cornell Medical College, New York, New York (United States); Chen, Margaret [Department of Surgery, Weill Cornell Medical College, New York, New York (United States); Nori, Dattatreyudu; Chao, K.S. Clifford [Department of Radiation Oncology, Weill Cornell Medical College, New York, New York (United States); Chen, Allen M. [Department of Radiation Oncology, University of California Davis Cancer Center, Sacramento, California (United States); Chen, Steven L. [Department of Surgery, University of California Davis Cancer Center, Sacramento, California (United States)

2012-09-01

Purpose: Pure tubular carcinoma of the breast (PTCB) represents a distinct subtype of invasive ductal carcinoma (IDC) that is generally thought to be associated with better prognosis than even low-grade IDC. There has been controversy as to the role of adjuvant radiation therapy (RT) in this population. We hypothesized that adjuvant RT would demonstrate a survival improvement. Methods and Materials: We queried the Surveillance, Epidemiology and End Results database for the years 1992-2007 to identify patients with pure tubular carcinomas of the breast. Patient demographics, tumor characteristics, and surgical and RT treatments were collected. Survival analysis was performed using the Kaplan-Meier method for univariate comparisons and Cox proportional hazards modeling for multivariate comparisons, stratifying on the basis of age with a cutoff age of 65. Results: A total of 6465 patients were identified: 3624 (56.1%) patients underwent lumpectomy with RT (LUMP+RT), 1525 (23.6%) patients underwent lumpectomy alone (LUMP), 1266 (19.6%) patients received mastectomy alone (MAST), and 50 (0.8%) patients underwent mastectomy with RT (MAST+RT). When we compared the LUMP+RT and LUMP groups directly, those receiving adjuvant RT tended to be younger and were less likely to be hormone receptor-positive. Overall survival was 95% for LUMP+RT and 90% for LUMP patients at 5 years. For those 65 or younger, the absolute overall survival benefit of LUMP+RT over LUMP was 1% at 5 years and 3% at 10 years. On stratified multivariate analysis, adjuvant RT remained a significant predictor in both age groups (P=.003 in age {<=}65 and P=.04 in age >65 patients). Other significant unfavorable factors were older age and higher T stage (age >65 only). Conclusions: Since sufficiently powered large scale clinical trials are unlikely, we would recommend that adjuvant radiation be considered in PTCB patients age 65 or younger, although consideration of the small absolute survival benefit is

Radiation sterilization of pharmaceuticals and biomedical products

International Nuclear Information System (INIS)

Blackburn, R.; Iddon, B.; Moore, J.S.; Phillips, G.O.; Power, D.M.; Woodward, T.W.

1975-01-01

Sterilization of pharmaceuticals by radiation is accompanied by chemical degradation which must be eliminated or minimised if the method is to be successfully applied. In order to devise ways in which the pharmaceutical can be protected it is necessary to know the yield and nature of the decomposition products, the mechanisms by which degradation occurs, and the rate constants for the reactions involved. We have obtained such data for a variety of pharmaceutical compounds, viz. vitamin B12, benzyl penicillin, sulphonamides, indoles, heparin, alginates and phenylmercurics, both in the solid state and in aqueous solution. The scope and limitations of radiation sterilization are discussed in the light of these results. (author)

Decomposition of persistent pharmaceuticals in wastewater by ionizing radiation

International Nuclear Information System (INIS)

Kimura, Atsushi; Osawa, Misako; Taguchi, Mitsumasa

2012-01-01

Pharmaceuticals in wastewater were treated by the combined method of activated sludge and ionizing radiation in laboratory scale. Oseltamivir, aspirin, and ibuprofen at 5 μmol dm −3 in wastewater were decomposed by the activated sludge at reaction time for 4 h. Carbamazepine, ketoprofen, mefenamic acid, clofibric acid, and diclofenac were not biodegraded completely, but were eliminated by γ-ray irradiation at 2 kGy. The rate constants of the reactions of these pharmaceuticals with hydroxyl radicals were estimated by the competition reaction method to be 4.0–10×10 9 mol −1 dm 3 s −1 . Decompositions of the pharmaceuticals in wastewater by ionizing radiation were simulated by use of the rate constants and the amount of total organic carbon as parameters. Simulation curves of concentrations of these pharmaceuticals as a function of dose described the experimental data, and the required dose for the elimination of them in wastewater by ionizing radiation can be estimated by this simulation. - Highlights: ► We treat pharmaceuticals in wastewater by activated sludge and ionizing radiation. ► Activated sludge decreases the amounts of total organic carbons in wastewater. ► Pharmaceuticals were decomposed by γ-ray irradiation at 2 kGy. ► We construct simulation for treatment of pharmaceuticals by ionizing radiation.

The pharmaceutical sector inquiry: 'Hamlet' in a nutshell.

Science.gov (United States)

den Exter, André

2010-03-01

In July 2009, the European Commission (DG Competition) published a Communication on the pharmaceutical sector. This inquiry was launched because there were some indications that competition in the pharmaceutical market in the European Union might not be working well. The report examines the reasons for the observed delay. This article analyses the outcomes from a critical standpoint, arguing in favour of enhanced 'soft law' accountability mechanisms in the pharmaceutical sector, defending conditional patenting and the introduction of a Community patent.

Polymers in life sciences: Pharmaceutical and biomedical applications

Science.gov (United States)

Barba, Anna Angela; Dalmoro, Annalisa; d'Amore, Matteo; Lamberti, Gaetano; Cascone, Sara; Titomanlio, Giuseppe

2015-12-01

This paper deals with the work done by prof. Titomanlio and his group in the fields of pharmaceutical and biomedical applications of polymers. In particular, the main topics covered are: i) controlled drug release from pharmaceuticals based on hydrogel for oral delivery of drugs; ii) production and characterization of micro and nanoparticles based on stimuli-responsive polymers; iii) use of polymers for coronary stent gel-paving; iv) design and realization of novel methods (in-vitro and in-silico) to test polymer-based pharmaceuticals.

Recurrent malignant pilomatrixoma invading the cranial cavity: improved local control with adjuvant radiation

International Nuclear Information System (INIS)

Aherne, N. J.; Fitzpatrick, D. A.; Armstrong, J. G.; Gibbons, D.; Collins, C. D.

2009-01-01

Full text: We report the case of a 41-year-old mentally retarded male with recurrent pilomatrix carcinoma of the occipital region which invaded the occipital bone, left cerebellum and left temporal lobe. At his initial presentation the patient had a craniotomy and subtotal excision of the lesion with positive margins. He received no adjuvant therapy. After an early intracranial recurrence he had subtotal debulking and was referred for external beam radiotherapy. At 27 months follow-up after adjuvant external beam radiotherapy the intracranial component has not progressed and the patient remains clinically well

Intravenous or oral administration of vinorelbine in adjuvant chemotherapy with cisplatin and vinorelbine for resected NSCLC

DEFF Research Database (Denmark)

Sorensen, Steffen Filskov; Carus, Andreas; Meldgaard, Peter

2015-01-01

OBJECTIVES: Cisplatin and vinorelbine given intravenously is a well-established adjuvant chemotherapy regimen after surgery for early-stage NSCLC. Vinorelbine can also be administered orally. However, the efficacy of orally administrated vinorelbine in adjuvant treatment of NSCLC is unknown. We...... University Hospital (Denmark) from 2005 to 2012 for adjuvant chemotherapy after surgery for NSCLC. RESULTS AND CONCLUSION: Of the 265 patients included in this study, 126 patients received i.v. and 139 received p.o. vinorelbine/cisplatin. The two groups were comparable with respect to important baseline....... In conclusion we observed that intravenous or oral administration of vinorelbine in combination with cisplatin after surgery for NSCLC appear equally effective in terms of overall and disease-free survival....

Drivers of peak sales for pharmaceutical brands

NARCIS (Netherlands)

Fischer, Marc; Leeflang, Peter S. H.; Verhoef, Peter C.

2010-01-01

Peak sales are an important metric in the pharmaceutical industry. Specifically, managers are focused on the height-of-peak-sales and the time required achieving peak sales. We analyze how order of entry and quality affect the level of peak sales and the time-to-peak-sales of pharmaceutical brands.

Meta-Analysis on Randomized Controlled Trials of Vaccines with QS-21 or ISCOMATRIX Adjuvant : Safety and Tolerability

NARCIS (Netherlands)

Bigaeva, Emilia; Doorn, Eva van; Liu, Heng; Hak, Eelko

2016-01-01

BACKGROUND AND OBJECTIVES: QS-21 shows in vitro hemolytic effect and causes side effects in vivo. New saponin adjuvant formulations with better toxicity profiles are needed. This study aims to evaluate the safety and tolerability of QS-21 and the improved saponin adjuvants (ISCOM, ISCOMATRIX and

Results of adjuvant chemo radiation after curative surgery for gastric cancer. A retrospective study

International Nuclear Information System (INIS)

Muller, Bettina; Balbontin, Paulina; Trujillo, Cristian; Becerra, Sergio; Sola, Antonio; Neveu, Rodrigo; Fernandez, Roberto; Buchholtz, Martin; Villanueva, Luis; Cerda, Berta

2009-01-01

Background: Survival rates after curative surgery for gastric cancer are disappointing. Therefore adjuvant therapeutic strategies are required. Aim: To analyze survival and side effects of treatment among gastric cancer patients treated with adjuvant chemoradiotherapy after curative resection of gastric adenocarcinoma. Material and methods: Retrospective review of medical records of 74 patients aged 20 to 74 years, treated with complete resection of gastric adenocarcinoma followed by adjuvant chemo radiation. Survival analysis was based on the records and information from the National Mortality Registry. Results: Five years survival fluctuated from 50% among patients in stage 1B to 25% among those is stage IV. Significant acute toxicity was observed in 23 patients (31%). No patients died due to acute toxicity. Eleven patients (16.4%) developed significant late toxicity, with two possible deaths related to treatment. Conclusions: Postoperative chemoradiotherapy is feasible in our experience. Continuos infusion of 5- fluoruracil is recommended to reduce toxicity

Synthetic mast-cell granules as adjuvants to promote and polarize immunity in lymph nodes

Science.gov (United States)

St. John, Ashley L.; Chan, Cheryl Y.; Staats, Herman F.; Leong, Kam W.; Abraham, Soman N.

2012-03-01

Granules of mast cells (MCs) enhance adaptive immunity when, on activation, they are released as stable particles. Here we show that submicrometre particles modelled after MC granules augment immunity when used as adjuvants in vaccines. The synthetic particles, which consist of a carbohydrate backbone with encapsulated inflammatory mediators such as tumour necrosis factor, replicate attributes of MCs in vivo including the targeting of draining lymph nodes and the timed release of the encapsulated mediators. When used as an adjuvant during vaccination of mice with haemagglutinin from the influenza virus, the particles enhanced adaptive immune responses and increased survival of mice on lethal challenge. Furthermore, differential loading of the particles with the cytokine IL-12 directed the character of the response towards Th1 lymphocytes. The synthetic MC adjuvants replicate and enhance the functions of MCs during vaccination, and can be extended to polarize the resulting immunity.

Treatment results of adjuvant radiotherapy and salvage radiotherapy after radical prostatectomy for prostate cancer

International Nuclear Information System (INIS)

Wadasaki, Koichi; Kaneyasu, Yuko; Kenjo, Masahiro; Matsuura, Kanji; Murakami, Yuji; Hashimoto, Yasutoshi; Ito, Katsuhide; Kiriu, Hiroshi; Ito, Atsushi

2007-01-01

The indications for and the efficacy of radiation therapy after radical operation for patients with prostate cancer are not clear. We analyzed the treatment results of adjuvant radiotherapy and salvage radiotherapy after radical prostatectomy. Between September 1997 and November 2004, 57 patients received adjuvant radiotherapy or salvage radiotherapy after radical prostatectomy. Fifteen patients received radiation therapy because of positive margins and/or extracapsular invasion in surgical specimens (adjuvant group). Forty-two patients received radiation therapy because of rising prostate-specific antigen (PSA) during follow-up (salvage group). Radiation therapy was delivered to the fossa of the prostate±seminal vesicles by a three-dimensional (3-D) conformal technique to a total dose of 60-66 Gy (median, 60 Gy). Biochemical control was defined as the maintenance of a PSA level of less than 0.2 ng/ml. The median follow-up period after radiation therapy was 33 months (range, 12-98 months). Three-year biochemical control rates were 87% for the adjuvant group and 61% for the salvage group. For patients in the salvage group treated without hormone therapy, the preradiation PSA value was the most significant factor for the biochemical control rate. The 3-year biochemical control rate was 93% in patients whose preradiation PSA was 0.5 ng/ml or less and 29% in patients whose preradiation PSA was more than 0.5 ng/ml. No severe adverse effects (equal to or more than grade 3) were seen in treated patients. Radiation therapy after radical prostatectomy seemed to be effective for adjuvant therapy and for salvage therapy in patients with a preradiation PSA of 0.5 ng/ml or less. Also, radiation to the fossa of the prostate±seminal vesicles, to a total dose of 60-66 Gy, using a three-dimensional (3-D) conformal technique, seemed to be safe. (author)

Trastuzumab re-treatment following adjuvant trastuzumab and the importance of distant disease-free interval: the HERA trial experience.

Science.gov (United States)

Metzger-Filho, Otto; de Azambuja, Evandro; Procter, Marion; Krieguer, Magalie; Smith, Ian; Baselga, Jose; Cameron, David; Untch, Michael; Jackisch, Christian; Bell, Richard; Gianni, Luca; Goldhirsch, Aron; Piccart, Martine; Gelber, Richard D

2016-01-01

This retrospective analysis conducted using data from patients enrolled onto the Herceptin Adjuvant has two objectives: The first is to evaluate the impact of the time interval between the end of adjuvant trastuzumab and distant recurrence (TDRI) upon overall survival (OS). The second is to describe the duration of trastuzumab-based regimens in the metastatic setting for patients previously treated with adjuvant trastuzumab. The first objective included 187 patients treated with adjuvant trastuzumab and diagnosed with distant recurrence at 4-year median follow-up. The second objective included data from questionnaires sent to investigators retreating patients with trastuzumab upon distant recurrence: 144 of 156 questionnaires were returned (93 %), and 90 patients were selected based on available clinical information and consent for subsequent studies. There was no statistically significant relationship between TDRI following 1 year of adjuvant trastuzumab and OS from distant recurrence: hazard ratio 0.991, p = 0.46. The median OS from distant recurrence was numerically longer among patients with a TDRI of ≥12 months (n = 103) than information beyond disease progression should be included in future clinical studies.

[A Case of Advanced Transverse Colon Cancer with Nephrotic Syndrome Treated with Curative Resection and Complete Adjuvant Chemotherapy].

Science.gov (United States)

Sato, Nobutaka; Fuyuno, Seiya; Hatada, Teppei; Furuhashi, Takashi; Abe, Toshihiko

2017-05-01

A 74-year-old woman was diagnosed as having transverse colon cancer after diagnosis of nephrotic syndrome caused by membranous nephropathy. Although she had hypoproteinemia and hypoalbuminemia, we judged that she had no major nutritional problem. In previous, similar case reports, the use of human serum albumin and fresh-frozen plasma was suggested to be important to avoid complications in the perioperative period. Thus, we used the same in our patient in the perioperative period. In addition, we paid special attention to perioperative nutrition management and used total parenteral nutrition in perioperative period. We performed laparoscopic assisted right hemicolectomy. On the 15th day after the surgical resection, the patient was discharged without any problems. We considered that postoperative adjuvant chemotherapy with XELOX (CapeOX)should be performed because the TNM pathological stage was pStage III b. Regarding adjuvant chemotherapy for gastrointestinal cancer with nephrotic syndrome, no previous reports detailed the indications for postoperative adjuvant chemotherapy. Upon introduction of adjuvant chemotherapy, we determined adaptation in accordance with the general adaptation criteria. While observing the patient's progress with a nephrologist, we safely completed the scheduled 8 courses adjuvant chemotherapy.

Role of Adjuvant Radiotherapy for Stage II Thymoma After Complete Tumor Resection

International Nuclear Information System (INIS)

Chen Yidong; Feng Qinfu; Lu Haizhen; Mao Yousheng; Zhou Zongmei; Ou Guangfei; Wang Mei; Zhao Jun; Zhang Hongxing; Xiao Zefen; Chen Dongfu; Liang Jun; Zhai Yirui; Wang Luhua; He Jie

2010-01-01

Purpose: To determine whether patients with Masaoka stage II thymoma benefit from adjuvant radiation therapy after complete tumor resection. Methods and Materials: A total of 107 patients with stage II thymoma who underwent complete resection of their tumors between September 1964 and October 2006 were retrospectively analyzed. Sixty-six patients were treated with adjuvant radiotherapy, and 41 patients received surgery alone. Results: Eight patients (7.5%) had a relapse of their disease, including two patients (4.5%) who had surgery alone, and 6 patients (9.5%) who had adjuvant radiation therapy. Disease-free survival rates at 5 and 10 years were 92.3% and 82.6%, respectively, for the surgery-plus-radiation group, and 97.6% and 93.1%, respectively, for the group that underwent surgery alone (p = 0.265). Disease-specific survival rates at 5 and 10 years were 96.4% and 89.3%, respectively, for the surgery-plus-radiation group and 97.5% and 97.5% for the surgery group (p = 0.973). On univariate analysis, patients with type B3 thymomas had the lowest disease-free survival rates among all subtypes (p = 0.001), and patients with large thymomas (>7 cm) had lower disease-specific survival rates than those with small tumors (<7 cm) (p = 0.017). On multivariate analysis, histological type (type B3) thymoma was a significant independent prognostic factor. Conclusions: Adjuvant radiotherapy after complete tumor resection for patients with stage II thymoma did not significantly reduce recurrence rates or improve survival rates. Histological type (type B3) thymoma was a significant independent prognostic factor. Further investigation should be carried out using a multicenter randomized or controlled study.

Nanoparticulate STING agonists are potent lymph node-targeted vaccine adjuvants.

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Hanson, Melissa C; Crespo, Monica P; Abraham, Wuhbet; Moynihan, Kelly D; Szeto, Gregory L; Chen, Stephanie H; Melo, Mariane B; Mueller, Stefanie; Irvine, Darrell J

2015-06-01

Cyclic dinucleotides (CDNs) are agonists of stimulator of IFN genes (STING) and have potential as vaccine adjuvants. However, cyclic di-GMP (cdGMP) injected s.c. shows minimal uptake into lymphatics/draining lymph nodes (dLNs) and instead is rapidly distributed to the bloodstream, leading to systemic inflammation. Here, we encapsulated cdGMP within PEGylated lipid nanoparticles (NP-cdGMP) to redirect this adjuvant to dLNs. Compared with unformulated CDNs, encapsulation blocked systemic dissemination and markedly enhanced dLN accumulation in murine models. Delivery of NP-cdGMP increased CD8+ T cell responses primed by peptide vaccines and enhanced therapeutic antitumor immunity. A combination of a poorly immunogenic liposomal HIV gp41 peptide antigen and NP-cdGMP robustly induced type I IFN in dLNs, induced a greater expansion of vaccine-specific CD4+ T cells, and greatly increased germinal center B cell differentiation in dLNs compared with a combination of liposomal HIV gp41 and soluble CDN. Further, NP-cdGMP promoted durable antibody titers that were substantially higher than those promoted by the well-studied TLR agonist monophosphoryl lipid A and comparable to a much larger dose of unformulated cdGMP, without the systemic toxicity of the latter. These results demonstrate that nanoparticulate delivery safely targets CDNs to the dLNs and enhances the efficacy of this adjuvant. Moreover, this approach can be broadly applied to other small-molecule immunomodulators of interest for vaccines and immunotherapy.

Liposome-Based Adjuvants for Subunit Vaccines: Formulation Strategies for Subunit Antigens and Immunostimulators

Directory of Open Access Journals (Sweden)

Signe Tandrup Schmidt

2016-03-01

Full Text Available The development of subunit vaccines has become very attractive in recent years due to their superior safety profiles as compared to traditional vaccines based on live attenuated or whole inactivated pathogens, and there is an unmet medical need for improved vaccines and vaccines against pathogens for which no effective vaccines exist. The subunit vaccine technology exploits pathogen subunits as antigens, e.g., recombinant proteins or synthetic peptides, allowing for highly specific immune responses against the pathogens. However, such antigens are usually not sufficiently immunogenic to induce protective immunity, and they are often combined with adjuvants to ensure robust immune responses. Adjuvants are capable of enhancing and/or modulating immune responses by exposing antigens to antigen-presenting cells (APCs concomitantly with conferring immune activation signals. Few adjuvant systems have been licensed for use in human vaccines, and they mainly stimulate humoral immunity. Thus, there is an unmet demand for the development of safe and efficient adjuvant systems that can also stimulate cell-mediated immunity (CMI. Adjuvants constitute a heterogeneous group of compounds, which can broadly be classified into delivery systems or immunostimulators. Liposomes are versatile delivery systems for antigens, and they can carefully be customized towards desired immune profiles by combining them with immunostimulators and optimizing their composition, physicochemical properties and antigen-loading mode. Immunostimulators represent highly diverse classes of molecules, e.g., lipids, nucleic acids, proteins and peptides, and they are ligands for pattern-recognition receptors (PRRs, which are differentially expressed on APC subsets. Different formulation strategies might thus be required for incorporation of immunostimulators and antigens, respectively, into liposomes, and the choice of immunostimulator should ideally be based on knowledge regarding the

Definitive and adjuvant radiotherapy for sinonasal squamous cell carcinomas: a single institutional experience

International Nuclear Information System (INIS)

Duru Birgi, Sumerya; Teo, Mark; Dyker, Karen E.; Sen, Mehmet; Prestwich, Robin J D

2015-01-01

The aim of this study was to evaluate the disease outcomes of patients treated with definitive and adjuvant radiotherapy for squamous cell carcinomas of the nasal cavity and paranasal sinuses in a single institution. Between 2007–2012 patients were retrospectively identified from electronic databases who had undergone surgery and adjuvant radiotherapy or definitive radiotherapy for sinonasal squamous cell carcinomas with curative intent. Fourty three patients with sinonasal squamous cell carcinoma were identified (22 nasal cavity, 21 paranasal sinuses). 31/43 (72 %) had T3 or T4 disease; nodal stage was N0 in 38, N1 in 4, Na/b in 0 and N2c in 1 patient. Median age was 67 years (range 41–86). 18 (42 %) received definitive and 25 (58 %) adjuvant radiotherapy. Radiotherapy was delivered using either conventional radiotherapy (n = 39) or intensity modulated radiotherapy (n = 4). Elective neck radiotherapy was delivered to two patients. Chemotherapy was delivered to 6/43 (14 %) of patients. Two-year local control, regional control, distant metastases free survival, progression free survival, cause specific survival and overall survival were 81 %, 90 %, 95 %, 71 %, 84 % and 80 % respectively. There was no significant difference in outcome comparing patients who underwent surgery and adjuvant radiotherapy with patients receiving definitive radiotherapy (2 year locoregional disease free survival 75 % and 70 % respectively, p = 0.98). Pooly differentiated tumours were significantly associated with inferior disease outcomes. Local, regional, combined local and regional, and distant failure occurred in 7 (16 %), 3 (7 %), 1 (2 %) and 2 (5 %) of patients; all 3 regional recurrences were in patients with nasal cavity squamous cell carcinomas who had not undergone elective neck treatment. Definitive or adjuvant radiotherapy provides an effective treatment for sinonasal malignancies. The main pattern of failure remains local, suggesting the need for investigation of

Evaluation of adjuvant chemoradiation therapy for ampullary adenocarcinoma: the Johns Hopkins Hospital - Mayo Clinic collaborative study

International Nuclear Information System (INIS)

Narang, Amol K; Haddock, Michael G; Donohue, John H; Schulick, Richard D; Wolfgang, Christopher L; Cameron, John L; Herman, Joseph M; Miller, Robert C; Hsu, Charles C; Bhatia, Sumita; Pawlik, Timothy M; Laheru, Dan; Hruban, Ralph H; Zhou, Jessica; Winter, Jordan M

2011-01-01

The role of adjuvant chemoradiation therapy for ampullary carcinoma is unknown. Previous literature suggests that certain populations with high risk factors for recurrence may benefit from adjuvant chemoradiation. We combined the experience of two institutions to better delineate which patients may benefit from adjuvant chemoradiation. Patients who underwent curative surgery for ampullary carcinoma at the Johns Hopkins Hospital (n = 290; 1992-2007) and at the Mayo Clinic (n = 130; 1977-2005) were reviewed. Patients with <60 days of follow-up, metastatic disease at surgery, or insufficient pathologic data were excluded. The final combined study consisted of 186 patients (n = 104 Johns Hopkins, n = 82 Mayo). Most patients received 5-FU based chemoradiation with conformal radiation. Cox proportional hazards models were used for survival analysis. Median overall-survival was 39.9 months with 2- and 5-year survival rates of 62.4% and 39.1%. On univariate analysis, adverse prognostic factors for overall survival included T3/T4 stage disease (RR = 1.86, p = 0.002), node positive status (RR = 3.18, p < 0.001), and poor histological grade (RR = 1.69, p = 0.011). Patients who received adjuvant chemoradiation (n = 66) vs. surgery alone (n = 120) showed a higher rate of T3/T4 stage disease (57.6% vs. 30.8%, P < 0.001), lymph node involvement (72.7% vs. 30.0%, P < 0.001), and close or positive margins (4.6% vs. 0.0%, P = 0.019). Five year survival rates among node negative and node positive patients were 58.7% and 18.4% respectively. When compared with surgery alone, use of adjuvant chemoradiation improved survival among node positive patients (mOS 32.1 vs. 15.7 mos, 5 yr OS: 27.5% vs. 5.9%; RR = 0.47, P = 0.004). After adjusting for adverse prognostic factors on multivariate analysis, patients treated with adjuvant chemoradiation demonstrated a significant survival benefit (RR = 0.40, P < 0.001). Disease relapse occurred in 37.1% of all patients, most commonly metastatic

Health risks of counterfeit pharmaceuticals.

Science.gov (United States)

ten Ham, Martijn

2003-01-01

Pharmaceutical products are not exempt from the practice of counterfeiting. In recent years, many reports have become available demonstrating the presence of fake medicines on the market. Several studies have demonstrated that they are quite often of bad quality. It is estimated that 5% of all world trade in branded goods is counterfeit, leading to huge financial losses for the pharmaceutical industry. But much more important, from a public health point of view, is that history has shown that such products may lead to a great health risk. The essence of counterfeit products and the reason they are so dangerous is the complete absence of quality control, since they are often indistinguishable from the genuine product. The existence of counterfeit drugs has long been ignored both by the pharmaceutical industry and by drug regulatory authorities. At present initiatives are being taken, nationally and internationally, to curb counterfeiting. It is now realised that a strong regulatory agency is essential, but the initiatives can only be successful if all parties concerned actively co-operate.

Marketing concepts for pharmaceutical service development.

Science.gov (United States)

Grauer, D W

1981-02-01

Marketing concepts as a mechanism to help pharmacy develop, communicate, and sell future pharmaceutical services to consumers are discussed. Pharmacy as a profession must define itself broadly to take advantage of future growth opportunities. These growth opportunities will be realized from unmet health-care needs and changing consumer life style trends and values. New services must therefore be oriented toward consumers (i.e., patients, health professionals, and third-party agencies) to gain acceptance. Dispensing and drug-knowledge-distribution pharmaceutical services are reviewed by a product life cycle analysis of sales profits versus time. A marketing mix for new pharmaceutical services is developed consisting of service, price, distribution, and promotion strategies. Marketing can encompass those key elements necessary to meet the organizational goals of pharmacy and provide a systematic, disciplined approach for presenting a new service to consumers.

Adjuvant radiotherapy with brachytherapy boost in soft tissue sarcomas

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Annalisa Cortesi

2017-06-01

Full Text Available Purpose: The standard primary treatment for soft tissue sarcoma (STS is a wide surgical resection, preceded or followed by radiotherapy. Purpose of this retrospective study was to assess the efficacy of perioperative brachytherapy (BRT plus postoperative external beam radiation therapy (EBRT in patients with intermediate-high risk STS. Material and methods : BRT delivered dose was 20 Gy. External beam radiation therapy was delivered with 3D-technique using multiple beams. The prescribed dose was 46 Gy to the PTV. Neoadjuvant and adjuvant chemotherapy (CHT was used in patients with potentially chemosensitive histological subtypes. The primary aim of the study was to analyze overall survival (OS and local control (LC in a large patient population treated with surgery, perioperative BRT, and adjuvant EBRT ± CHT. Secondary objective was to identify prognostic factors for patients outcome in terms of LC, disease-free survival (DFS, and OS. Results : From 2000 to 2011, 107 patients presenting 2-3 grade (FNLCC primary or recurrent STS were treated with surgery, perioperative BRT, and adjuvant EBRT ± CHT. Five-year LC and OS were 80.9% and 87.4%, respectively. At univariate analysis, a higher LC was recorded in primary vs. recurrent tumors (p = 0.015, and in lower limb tumors vs. other sites (p = 0.027. An improved DFS was recorded in patients with lower limb tumors vs. other sites (p = 0.034. Conclusions : The combination of BRT and EBRT was able to achieve satisfactory results even in a patients population with intermediate-high risk STS. Patients with recurrent or other than lower limb sited tumors show a worse LC.

Adjuvant radiotherapy with brachytherapy boost in soft tissue sarcomas

Science.gov (United States)

Cortesi, Annalisa; Galuppi, Andrea; Arcelli, Alessandra; Romani, Fabrizio; Mattiucci, Gian Carlo; Bianchi, Giuseppe; Ferrari, Stefano; Ferraro, Andrea; Farioli, Andrea; Gambarotti, Marco; Righi, Alberto; Macchia, Gabriella; Deodato, Francesco; Cilla, Savino; Buwenge, Milly; Valentini, Vincenzo; Morganti, Alessio Giuseppe; Donati, Davide; Cammelli, Silvia

2017-01-01

Purpose The standard primary treatment for soft tissue sarcoma (STS) is a wide surgical resection, preceded or followed by radiotherapy. Purpose of this retrospective study was to assess the efficacy of perioperative brachytherapy (BRT) plus postoperative external beam radiation therapy (EBRT) in patients with intermediate-high risk STS. Material and methods BRT delivered dose was 20 Gy. External beam radiation therapy was delivered with 3D-technique using multiple beams. The prescribed dose was 46 Gy to the PTV. Neoadjuvant and adjuvant chemotherapy (CHT) was used in patients with potentially chemosensitive histological subtypes. The primary aim of the study was to analyze overall survival (OS) and local control (LC) in a large patient population treated with surgery, perioperative BRT, and adjuvant EBRT ± CHT. Secondary objective was to identify prognostic factors for patients outcome in terms of LC, disease-free survival (DFS), and OS. Results From 2000 to 2011, 107 patients presenting 2-3 grade (FNLCC) primary or recurrent STS were treated with surgery, perioperative BRT, and adjuvant EBRT ± CHT. Five-year LC and OS were 80.9% and 87.4%, respectively. At univariate analysis, a higher LC was recorded in primary vs. recurrent tumors (p = 0.015), and in lower limb tumors vs. other sites (p = 0.027). An improved DFS was recorded in patients with lower limb tumors vs. other sites (p = 0.034). Conclusions The combination of BRT and EBRT was able to achieve satisfactory results even in a patients population with intermediate-high risk STS. Patients with recurrent or other than lower limb sited tumors show a worse LC. PMID:28725250

Chemotherapy-related amenorrhea after adjuvant paclitaxel-trastuzumab (APT trial).

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Ruddy, Kathryn J; Guo, Hao; Barry, William; Dang, Chau T; Yardley, Denise A; Moy, Beverly; Marcom, P Kelly; Albain, Kathy S; Rugo, Hope S; Ellis, Matthew J; Shapira, Iuliana; Wolff, Antonio C; Carey, Lisa A; Overmoyer, Beth A; Hudis, Clifford; Krop, Ian E; Burstein, Harold J; Winer, Eric P; Partridge, Ann H; Tolaney, Sara M

2015-06-01

Chemotherapy-related amenorrhea (CRA) is associated with infertility and menopausal symptoms. Learning how frequently paclitaxel and trastuzumab cause amenorrhea is important. Most other adjuvant breast cancer therapies induce CRA in approximately 50 % of all premenopausal recipients [1]. 410 patients enrolled on the APT Trial, a single-arm phase 2 adjuvant study of 12 weeks of paclitaxel and trastuzumab followed by nine months of trastuzumab monotherapy. Eligible patients had ≤3 cm node-negative HER2 + breast cancers. Premenopausal enrollees were asked to complete menstrual surveys every 3-12 months for 72 months. Women who responded to at least one survey at least 15 months after chemotherapy initiation (and who did not undergo hysterectomy and/or bilateral oophorectomy or receive ovarian suppressing medications prior to 15 months) were included in this analysis. A participant was defined as having amenorrhea in follow-up if her self-reported last menstrual period at last follow-up was greater than 12 months prior to the survey. Among the 64 women in the evaluable population (median age at study entry 44 years, range 27-52 years), the median time between chemotherapy initiation and last menstrual survey was 51 months (range 16-79). 18 of 64 women (28 %, 95 % CI 18-41 %) were amenorrheic at that time point. Amenorrhea rates among premenopausal women treated with adjuvant paclitaxel and trastuzumab for early stage breast cancer appear lower than those seen historically with standard alkylator-based breast cancer regimens. Future studies are needed to understand the impact of this regimen on related issues of fertility and menopausal symptoms.

Adjuvant Treatment after Surgery in Stage IIIA Endometrial Adenocarcinoma

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Yoon, Mee Sun; Huh, Seung Jae; Kim, Hak Jae; Kim, Young Seok; Kim, Yong Bae; Kim, Joo-Young; Lee, Jong-Hoon; Kim, Hun Jung; Cha, Jihye; Kim, Jin Hee; Kim, Juree; Yoon, Won Sup; Choi, Jin Hwa; Chun, Mison; Choi, Youngmin; Lee, Kang Kyoo; Kim, Myungsoo; Jeong, Jae-Uk; Chang, Sei Kyung; Park, Won

2016-01-01

Purpose We evaluated the role of adjuvant therapy in stage IIIA endometrioid adenocarcinoma patients who underwent surgery followed by radiotherapy (RT) alone or chemoradiotherapy (CTRT) according to risk group. Materials and Methods A multicenter retrospective study was conducted including patients with surgical stage IIIA endometrial cancertreated by radical surgery and adjuvant RT or CTRT. Disease-free survival (DFS) and overall survival (OS) were analyzed. Results Ninety-three patients with stage IIIA disease were identified. Nineteen patients (20.4%) experienced recurrence, mostly distant metastasis (17.2%). Combined CTRT did not affect DFS (74.1% vs. 82.4%, p=0.130) or OS (96.3% vs. 91.9%, p=0.262) in stage IIIA disease compared with RT alone. Patients with age ≥ 60 years, grade G2/3, and lymphovascular space involvement had a significantly worse DFS and those variables were defined as risk factors. The high-risk group showed a significant reduction in 5-year DFS (≥ 2 risk factors) (49.0% vs. 88.0%, p < 0.001) compared with the low-risk group (< 2). Multivariate analysis confirmed that more than one risk factor was the only predictor of worse DFS (hazard ratio, 5.45; 95% confidence interval, 2.12 to 13.98; p < 0.001). Of patients with no risk factors, a subset treated with RT alone showed an excellent 5-year DFS and OS (93.8% and 100%, respectively). Conclusion We identified a low-risk subset of stage IIIA endometrioid adenocarcinoma patients who might be reasonable candidates for adjuvant RT alone. Further randomized studies are needed to determine which subset might benefit from combined CTRT. PMID:26511800

Adjuvant Ab Interno Tumor Treatment After Proton Beam Irradiation.

Science.gov (United States)

Seibel, Ira; Riechardt, Aline I; Heufelder, Jens; Cordini, Dino; Joussen, Antonia M

2017-06-01

This study was performed to show long-term outcomes concerning globe preservation in uveal melanoma patients after proton beam therapy with the main focus on outcomes according to different adjuvant ab interno surgical procedures. Retrospective cohort study. All patients treated with primary proton beam therapy for choroidal or ciliary body melanoma between June 1998 and June 2015 were included. A total of 2499 patients underwent primary proton beam therapy, with local tumor control and globe preservation rates of 95.9% and 94.8% after 5 years, respectively. A total of 110 (4.4%) patients required secondary enucleation. Unresponsive neovascular glaucoma was the leading cause of secondary enucleation in 78 of the 2499 patients (3.1%). The 5-year enucleation-free survival rate was 94.8% in the endoresection group, 94.3% in the endodrainage group, and 93.5% in the comparator group. The log-rank test showed P = .014 (comparator group vs endoresection group) and P = .06 (comparator group vs endodrainage-vitrectomy group). Patients treated with endoresection or endodrainage-vitrectomy developed less radiation retinopathy (30.5% and 37.4% after 5 years, P = .001 and P = .048 [Kaplan-Meier], respectively) and less neovascular glaucoma (11.6% and 21.3% after 5 years, P = .001 and P = .01 [Kaplan-Meier], respectively) compared with the comparator group (52.3% radiation retinopathy and 57.8% neovascular glaucoma after 5 years). This study suggests that in larger tumors the enucleation and neovascular glaucoma rates might be reduced by adjuvant surgical procedures. Although endoresection is the most promising adjuvant treatment option, the endodrainage-vitrectomy is recommended in patients who are ineligible for endoresection. Copyright © 2017 Elsevier Inc. All rights reserved.

New opportunities for biocatalysis: making pharmaceutical processes greener

DEFF Research Database (Denmark)

Woodley, John

2008-01-01

The pharmaceutical industry requires synthetic routes to be environmentally compatible as well as to fulfill the demands of process economics and product specification and to continually reduce development times. Biocatalysis has the potential to deliver 'greener' chemical syntheses, and in this ......The pharmaceutical industry requires synthetic routes to be environmentally compatible as well as to fulfill the demands of process economics and product specification and to continually reduce development times. Biocatalysis has the potential to deliver 'greener' chemical syntheses...... of biocatalysis for making pharmaceutical processes greener....

Lack of Prognostic Impact of Adjuvant Radiation on Oncologic Outcomes in Elderly Women with Breast Cancer.

Science.gov (United States)

Omidvari, Shapour; Talei, Abdolrasoul; Tahmasebi, Sedigheh; Moaddabshoar, Leila; Dayani, Maliheh; Mosalaei, Ahmad; Ahmadloo, Niloofar; Ansari, Mansour; Mohammadianpanah, Mohammad

2015-01-01

Radiotherapy plays an important role as adjuvant treatment in locally advanced breast cancer and in those patients who have undergone breast-conserving surgery. This study aimed to investigate the prognostic impact of adjuvant radiation on oncologic outcomes in elderly women with breast cancer. In this retrospective study, we reviewed and analyzed the characteristics, treatment outcome and survival of elderly women (aged ≥ 60 years) with breast cancer who were treated and followed-up between 1993 and 2014. The median follow up for the surviving patients was 38 (range 3-207) months. One hundred and seventy-eight patients with a median age of 74 (range 60-95) years were enrolled in the study. Of the total, 60 patients received postoperative adjuvant radiation (radiation group) and the remaining 118 did not (control group). Patients in the radiation group were significantly younger than those in the control group (P value=0.004). In addition, patients in radiation group had higher node stage (P value<0.001) and disease stage (P=0.003) and tended to have higher tumor grade (P=0.031) and received more frequent (P value <0.001) adjuvant and neoadjuvant chemotherapy compared to those in the control group. There was no statistically significant difference between two groups regarding the local control, disease-free survival and overall survival rates. In this study, we did not find a prognostic impact for adjuvant radiation on oncologic outcomes in elderly women with breast cancer.

Pharmaceutical care as a historical, normative-legal and social-economic category in the system of the population health and pharmaceutical care

Directory of Open Access Journals (Sweden)

G. L. Panfilova

2014-08-01

Full Text Available Aim. Terminological vagueness of the term «pharmaceutical care» in domestic legislative framework and scientific environment makes it impossible to introduce new forms and methods of providing pharmaceutical population in Ukraine effectively. In order to form the unified methodological approach to identify and order the use of the mentioned term, the results of organizational-economic studies in pharmacy and the existing legal framework have been analyzed. Methods and results. Using dialectical, historical, logical-semantic and other methods the basic stages in the development of pharmaceutical care have been established and definitions tree of the concept have been constructed. Conclusion. The results of these studies indicate the need for recognition and regulatory mapping integration (organizational and economic of the definition «pharmaceutical care» in domestic legislation and public health practice.

Adsorptive removal of selected pharmaceuticals by mesoporous silica SBA-15

International Nuclear Information System (INIS)

Bui, Tung Xuan; Choi, Heechul

2009-01-01

The removal of five selected pharmaceuticals, viz., carbamazepine, clofibric acid, diclofenac, ibuprofen, and ketoprofen was examined by batch sorption experiments onto a synthesized mesoporous silica SBA-15. SBA-15 was synthesized and characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), N 2 adsorption-desorption measurement, and point of zero charge (PZC) measurement. Pharmaceutical adsorption kinetics was rapid and occurred on a scale of minutes, following a pseudo-second-order rate expression. Adsorption isotherms were best fitted by the Freundlich isotherm model. High removal rates of individual pharmaceuticals were achieved in acidic media (pH 3-5) and reached 85.2% for carbamazepine, 88.3% for diclofenac, 93.0% for ibuprofen, 94.3% for ketoprofen, and 49.0% for clofibric acid at pH 3 but decreased with increase in pH. SBA-15 also showed high efficiency for removal of a mixture of 5 pharmaceuticals. Except for clofibric acid (35.6%), the removal of pharmaceuticals in the mixture ranged from 75.2 to 89.3%. Based on adsorption and desorption results, the mechanism of the selected pharmaceuticals was found to be a hydrophilic interaction, providing valuable information for further studies to design materials for the purpose. The results of this study suggest that mesoporous-silica-based materials are promising adsorbents for removing pharmaceuticals from not only surface water but also wastewater of pharmaceutical industrial manufactures.

Adsorptive removal of selected pharmaceuticals by mesoporous silica SBA-15

Energy Technology Data Exchange (ETDEWEB)

Bui, Tung Xuan, E-mail: bxtung@gist.ac.kr [Department of Environmental Science and Engineering, Gwangju Institute of Science and Technology (GIST), 261 Cheomdan-gwagiro, Buk-gu, Gwangju 500-712 (Korea, Republic of); Choi, Heechul, E-mail: hcchoi@gist.ac.kr [Department of Environmental Science and Engineering, Gwangju Institute of Science and Technology (GIST), 261 Cheomdan-gwagiro, Buk-gu, Gwangju 500-712 (Korea, Republic of)

2009-09-15

The removal of five selected pharmaceuticals, viz., carbamazepine, clofibric acid, diclofenac, ibuprofen, and ketoprofen was examined by batch sorption experiments onto a synthesized mesoporous silica SBA-15. SBA-15 was synthesized and characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), N{sub 2} adsorption-desorption measurement, and point of zero charge (PZC) measurement. Pharmaceutical adsorption kinetics was rapid and occurred on a scale of minutes, following a pseudo-second-order rate expression. Adsorption isotherms were best fitted by the Freundlich isotherm model. High removal rates of individual pharmaceuticals were achieved in acidic media (pH 3-5) and reached 85.2% for carbamazepine, 88.3% for diclofenac, 93.0% for ibuprofen, 94.3% for ketoprofen, and 49.0% for clofibric acid at pH 3 but decreased with increase in pH. SBA-15 also showed high efficiency for removal of a mixture of 5 pharmaceuticals. Except for clofibric acid (35.6%), the removal of pharmaceuticals in the mixture ranged from 75.2 to 89.3%. Based on adsorption and desorption results, the mechanism of the selected pharmaceuticals was found to be a hydrophilic interaction, providing valuable information for further studies to design materials for the purpose. The results of this study suggest that mesoporous-silica-based materials are promising adsorbents for removing pharmaceuticals from not only surface water but also wastewater of pharmaceutical industrial manufactures.

Pharmaceutical Distribution Market Channels in Poland

Directory of Open Access Journals (Sweden)

Agnieszka Woś

2009-09-01

Full Text Available Distribution on the pharmaceutical market in Poland is interesting and the most difficult sphere to manage. Numerous varied and specialized companies operating on the market cause that the processes of choosing middlemen in distribution channels are very complex. The hereby article presents the role and location of the companies operating within distribution channels on the pharmaceutical market. It draws attention to the development of non-pharmacy and non-wholesale sales channels.

Pharmaceutical cocrystals: walking the talk.

Science.gov (United States)

Bolla, Geetha; Nangia, Ashwini

2016-06-28

Pharmaceutical cocrystals belong to a sub-class of cocrystals wherein one of the components is a drug molecule (or an active pharmaceutical ingredient, API) and the second is a benign food or drug grade additive (generally regarded as safe, GRAS). The two components are hydrogen-bonded in a fixed stoichiometric ratio in the crystal lattice. In the past decade, pharmaceutical cocrystals have demonstrated significant promise in their ability to modify the physicochemical and pharmacokinetic properties of drug substances, such as the solubility and dissolution rate, bioavailability, particle morphology and size, tableting and compaction, melting point, physical form, biochemical and hydration stability, and permeability. In this feature review, we highlight some prominent examples of drug cocrystals which exhibit variable hardness/softness and elasticity/plasticity depending on coformer selection, improvement of solubility and permeability in the same cocrystal, increase of the melting point for solid formulation, enhanced color performance, photostability and hydration stability, and a longer half-life. Cocrystals of flavanoids and polyphenols can make improved pharmaceuticals and also extend to the larger class of nutraceuticals. The application of crystal engineering to assemble ternary cocrystals expands this field to drug-drug cocrystals which may be useful in multi-drug resistance, mitigating side effects of drugs, or attenuating/enhancing drug action synergistically by rational selection. The advent of new techniques for structural characterization beyond the standard X-ray diffraction will provide a better understanding of drug phases which are at the borderline of crystalline-amorphous nature and even newer opportunities in the future.

Metronomic Adjuvant Chemotherapy Improves Treatment Outcome in Nasopharyngeal Carcinoma Patients With Postradiation Persistently Detectable Plasma Epstein-Barr Virus Deoxyribonucleic Acid

Energy Technology Data Exchange (ETDEWEB)

Twu, Chih-Wen [Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Wang, Wen-Yi [Section of Basic Medicine, Department of Nursing, Hung Kuang University, Taichung, Taiwan (China); Chen, Chien-Chih [Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Liang, Kai-Li; Jiang, Rong-San [Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Wu, Ching-Te [Department of Radiation Oncology, Taichung Veterans General Hospital–Chiayi Branch, Chiayi, Taiwan (China); Shih, Yi-Ting [Department of Radiation Oncology, St. Martin De Porres Hospital, Chiayi, Taiwan (China); Lin, Po-Ju; Liu, Yi-Chun [Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Lin, Jin-Ching, E-mail: jclin@vghtc.gov.tw [Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Medicine, China Medical University, Taichung, Taiwan (China)

2014-05-01

Purpose: To investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus DNA (pEBV DNA) after curative radiation therapy plus induction/concurrent chemotherapy. Methods and Materials: The study population consisted of 625 NPC patients with available pEBV DNA levels before and after treatment. Eighty-five patients with persistently detectable pEBV DNA after 1 week of completing radiation therapy were eligible for this retrospective study. Of the 85 patients, 33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2 capsules twice daily) for 12 months with (n=4) or without (n=29) preceding intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin. The remaining 52 patients who did not receive adjuvant chemotherapy served as the control group. Results: Baseline patient characteristics at diagnosis (age, sex, pathologic type, performance status, T classification, N classification, and overall stage), as well as previous treatment modality, were comparable in both arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of 33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a significant reduction in distant failure (P=.0034) but not in local or regional recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio 0.27; 95% confidence interval 0.17-0.55; P<.0001). Conclusions: Our retrospective data showed that adjuvant chemotherapy can reduce distant failure and improve overall survival in NPC patients with persistently detectable pEBV DNA after curative radiation therapy plus induction/concurrent chemotherapy.

Metronomic Adjuvant Chemotherapy Improves Treatment Outcome in Nasopharyngeal Carcinoma Patients With Postradiation Persistently Detectable Plasma Epstein-Barr Virus Deoxyribonucleic Acid

International Nuclear Information System (INIS)