Mycotoxin Exposure and Renal Cell Carcinoma Risk: An Association Study in the EPIC European Cohort

Background: Mycotoxins have been suggested to contribute to a spectrum of adverse health effects in humans, including at low concentrations. The recognition of these food contaminants being carcinogenic, as co-occurring rather than as singularly present, has emerged from recent research. The aim of this study was to assess the potential associations of single and multiple mycotoxin exposures with renal cell carcinoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: Food questionnaire data from the EPIC cohort were matched to mycotoxin food occurrence data compiled by the European Food Safety Authority (EFSA) from European Member States to assess long-term dietary mycotoxin exposures, and to associate these with the risk of renal cell carcinoma (RCC, n = 911 cases) in 450,112 EPIC participants. Potential confounding factors were taken into account. Analyses were conducted using Cox's proportional hazards regression models to compute hazard ratios (HRs) and 95% confidence intervals (95% CIs) with mycotoxin exposures expressed as mu g/kg body weight/day. Results: Demographic characteristics differed between the RCC cases and non-cases for body mass index, age, alcohol intake at recruitment, and other dietary factors. In addition, the mycotoxin exposure distributions showed that a large proportion of the EPIC population was exposed to some of the main mycotoxins present in European foods such as deoxynivalenol (DON) and derivatives, fumonisins, Fusarium toxins, Alternaria toxins, and total mycotoxins. Nevertheless, no statistically significant associations were observed between the studied mycotoxins and mycotoxin groups, and the risk of RCC development. Conclusions: These results show an absence of statistically significant associations between long-term dietary mycotoxin exposures and RCC risk. However, these results need to be validated in other cohorts and preferably using repeated dietary exposure measurements. In addition, more occurrence data of, e.g., citrinin and fumonisins in different food commodities and countries in the EFSA database are a prerequisite to establish a greater degree of certainty

Immunogenicity of chimeric haemagglutinin-based, universal influenza virus vaccine candidates: interim results of a randomised, placebo-controlled, phase 1 clinical trial.

BackgroundInfluenza viruses cause substantial annual morbidity and mortality globally. Current vaccines protect against influenza only when well matched to the circulating strains. However, antigenic drift can cause considerable mismatches between vaccine and circulating strains, substantially reducing vaccine effectiveness. Moreover, current seasonal vaccines are ineffective against pandemic influenza, and production of a vaccine matched to a newly emerging virus strain takes months. Therefore, there is an unmet medical need for a broadly protective influenza virus vaccine. We aimed to test the ability of chimeric H1 haemagglutinin-based universal influenza virus vaccine candidates to induce broadly cross-reactive antibodies targeting the stalk domain of group 1 haemagglutinin-expressing influenza viruses.MethodsWe did a randomised, observer-blinded, phase 1 study in healthy adults in two centres in the USA. Participants were randomly assigned to one of three prime-boost, chimeric haemagglutinin-based vaccine regimens or one of two placebo groups. The vaccine regimens included a chimeric H8/1, intranasal, live-attenuated vaccine on day 1 followed by a non-adjuvanted, chimeric H5/1, intramuscular, inactivated vaccine on day 85; the same regimen but with the inactivated vaccine being adjuvanted with AS03; and an AS03-adjuvanted, chimeric H8/1, intramuscular, inactivated vaccine followed by an AS03-adjuvanted, chimeric H5/1, intramuscular, inactivated vaccine. In this planned interim analysis, the primary endpoints of reactogenicity and safety were assessed by blinded study group. We also assessed anti-H1 haemagglutinin stalk, anti-H2, anti-H9, and anti-H18 IgG antibody titres and plasmablast and memory B-cell responses in peripheral blood. This trial is registered with ClinicalTrials.gov, number NCT03300050.FindingsBetween Oct 10, 2017, and Nov 27, 2017, 65 participants were enrolled and randomly assigned. The adjuvanted inactivated vaccine, but not the live-attenuated vaccine, induced a substantial serum IgG antibody response after the prime immunisation, with a seven times increase in anti-H1 stalk antibody titres on day 29. After boost immunisation, all vaccine regimens induced detectable anti-H1 stalk antibody (2·2-5·6 times induction over baseline), cross-reactive serum IgG antibody, and peripheral blood plasmablast responses. An unsolicited adverse event was reported for 29 (48%) of 61 participants. Solicited local adverse events were reported in 12 (48%) of 25 participants following prime vaccination with intramuscular study product or placebo, in 12 (33%) of 36 after prime immunisation with intranasal study product or placebo, and in 18 (32%) of 56 following booster doses of study product or placebo. Solicited systemic adverse events were reported in 14 (56%) of 25 after prime immunisation with intramuscular study product or placebo, in 22 (61%) of 36 after immunisation with intranasal study product or placebo, and in 21 (38%) of 56 after booster doses of study product or placebo. Disaggregated safety data were not available at the time of this interim analysis.InterpretationThe tested chimeric haemagglutinin-based, universal influenza virus vaccine regimens elicited cross-reactive serum IgG antibodies that targeted the conserved haemagglutinin stalk domain. This is the first proof-of-principle study to show that high anti-stalk titres can be induced by a rationally designed vaccine in humans and opens up avenues for further development of universal influenza virus vaccines. On the basis of the blinded study group, the vaccine regimens were tolerable and no safety concerns were observed.FundingBill & Melinda Gates Foundation

Superior antigen-specific CD4+ T-cell response with AS03-adjuvantation of a trivalent influenza vaccine in a randomised trial of adults aged 65 and older

BACKGROUND: The effectiveness of trivalent influenza vaccines may be reduced in older versus younger adults because of age-related immunosenescence. The use of an adjuvant in such a vaccine is one strategy that may combat immunosenescence, potentially by bolstering T-cell mediated responses. METHODS: This observer-blind study, conducted in the United States (US) and Spain during the 2008-2009 influenza season, evaluated the effect of Adjuvant System AS03 on specific T-cell responses to a seasonal trivalent influenza vaccine (TIV) in >/=65 year-old adults.Medically-stable adults aged >/=65 years were randomly allocated to receive a single dose of AS03-adjuvanted TIV (TIV/AS03) or TIV. Healthy adults aged 18-40 years received only TIV. Blood samples were collected on Day 0, Day 21, Day 42 and Day 180. Influenza-specific CD4+ T cells, defined by the induction of the immune markers CD40L, IL-2, IFN-gamma, or TNF-alpha, were measured in ex vivo cultures of antigen-stimulated peripheral blood mononuclear cells. RESULTS: A total of 192 adults were vaccinated: sixty nine and seventy three >/=65 year olds received TIV/AS03 and TIV, respectively; and fifty 18 - 40 year olds received TIV. In the >/=65 year-old group on Day 21, the frequency of CD4+ T cells specific to the three vaccine strains was superior in the TIV/AS03 recipients to the frequency in TIV (p /=65 year-old recipients of TIV/AS03 than in the 18 - 40 year old recipients of TIV on Days 21 (p = 0.006) and 42 (p = 0.011). CONCLUSION: This positive effect of AS03 Adjuvant System on the CD4+ T-cell response to influenza vaccine strains in older adults could confer benefit in protection against clinical influenza disease in this population. TRIAL REGISTRATION: (Clinicaltrials.gov.). NCT00765076

Adaptation and validation of a drug related problem classification tool in community pharmacy

Aim of project/studyThe aims of the study were:1) To translate and adapt the PCNE drug related problems (DRP) classification tool (v.6.2.) to the Belgian community pharmacy setting2) To assess the content validity and the reliability of this classification toolMethodThe translated and adapted version of the tool was submitted to a group of 15 pharmacists, which reviewed the format and content of the items. Content validity indexes were calculated. After adaptation of the tool, 109 DRP were collected in community pharmacy and 56 of these DRP were submitted to 10 community pharmacists to test the inter-rater reliability of the tool.Result(s)The PCNE classification tool has been translated in french and adapted by adding 11 items in the section « causes » (mostly related to the logistics of the prescribing and dispensing process, and related to the behaviour of the patient), and 2 items in the section « interventions ». The process of content validation resulted in modifying the definitions of potential problem and manifest problem, and in adding 2 items in the section “causes”. The final adapted tool included 84 items classified in 4 sections (problems, causes, interventions and outcomes), with full instructions on how to use it. In term of reliability of the tool, the inter-rater agreement was very good between the pharmacists since it was of 90% for the majority of the items. However, the agreement for “potential problem”, “manifest problem” and “effect of drug treatment not optimal” was only of 59%, 61% and 69%, respectively, suggesting some lack of understanding for those items. Concerning the outcomes of pharmacist’s interventions, the agreement was of 80% for the item “problem totally solved”. A difference in pharmacist’s perception to consider that the intervention is sufficient to totally solve the DRP could explain this result. In conclusion, these results showed that the tool is reliable and has adequate validity to measure the frequency and the nature of DRP detected in a Belgian community pharmacy setting.info:eu-repo/semantics/publishe

Patient satisfaction on personalized counseling in community pharmacy in Belgium :a pilot study

Advices to the patient on medication is a key role of community pharmacists. Since several years, theBelgian Pharmacist Association (APB) developed patient information leaflets (PILs) helping pharmacists to satisfy thisrequirement. Written information about drug treatment has been shown to reinforce oral communication. Data concerningthe patients’ satisfaction about personalized counseling and PILs are lacking in Belgium. The aims of the study were toassess (1) the patients’ perception of their medication knowledge (2) their need of information (3) their satisfaction onpersonalized medication counseling(4) their perceived quality of PILs.Materials & Methods: Prospective study in 2 community pharmacies including patients with 3 or more prescribedmedications. Two structured interviews were realized on 21 patients, before and after personalized medicationcounseling (verbal counseling, PILs and medication schedule if not already used by patients). A total of 47 PILs wereprovided to the patients. Evaluation of PILs quality was based on the expanded EQIP tool [1]. Descriptive statistics wereused to analyze the results.Results: (1) 14%, 32%, 41%, 9%, and 4% of patient have a very good, good, medium, bad and very bad perception oftheir medication knowledge, respectively. 77% are rather satisfied on information received on medication. (2)Patients’need of information: 33% and 62% would like to be better informed about their disease and medication,respectively. The need of information mostly (> 50%) refers to therapeutic effect, side effect, contraindications andmedication interactions. Only 18% would like to receive a personalized counseling about their medication.(3) Afterpersonalized counseling, 81% of patients are fully satisfied with information received, 14% satisfied, and 5% unsatisfied.Concerning the verbal counseling, 33%, 57 %, and 10% of patients consider it as very important, rather important, notvery important, respectively. Similar results are obtained with written information. However, 90% of patients report that,usually, they never receive PILs from their pharmacist.(4) Using the criteria of the EQIP tool, the majority of the patients(> 50%) are fully satisfied with the content and structure of the PILs. 70% and 55% of patients reported the PILs to beuseful for their theoretical and practical medication knowledge, respectively.Discussion, Conclusion: This pilot study suggests a positive impact of personalized medication counseling onperceived patient knowledge. The majority of the patients are fully satisfied with verbal counseling and with PILsprovided. Pharmacists should promote PILs as a useful resource. Larger studies measuring the impact of thisintervention on patient competence and adherence need to be performed.info:eu-repo/semantics/publishe

Transmission d’information au pharmacien d’officine après hospitalisation du patient : élaboration d’une feuille de transfert, évaluation prospective de son effet et enquête sur les besoins d’information des pharmaciens

Introduction : La sortie de l’hôpital est une période à risque pour la continuité de la prise en charge médicamenteuse. Le pharmacien d’officine est souvent le premier professionnel de santé rencontré par le patient lors de son retour à son domicile. Le pharmacien clinicien est un acteur clé pour établir une communication de l’hôpital vers l’officine. Objectifs : 1) Développer, 2) évaluer l’effet d’une feuille de transfert préparée par le pharmacien clinicien à la sortie du patient et contenant des informations relatives au traitement médicamenteux pour le pharmacien d’officine et 3) quantifier les besoins en information des pharmaciens d’officine belges pour assurer la continuité des traitements après l’hospitalisation. Méthodes : 1) Une feuille de transfert a été développée sur base d’une revue de la littérature et des avis émis par des pharmaciens d’officine et cliniciens, des membres de l’Association Pharmaceutique Belge et du Comité d’éthique. 2) Une étude prospective a été menée chez des patients des services de gériatrie et d’orthopédie du Centre Hospitalier Universitaire Dinant-Godinne, quittant l’hôpital pour rejoindre leur domicile avec une feuille de transfert à remettre à leur pharmacien ; son utilisation, les raisons de non-utilisation, l’impact perçu et la satisfaction du pharmacien d’officine ont été évalués. 3) Une enquête en ligne, ouverte à tous les pharmaciens d’officine belges, a évalué leurs besoins en information. Résultats : 1) La version finale de la feuille de transfert inclus des éléments d’information relatifs à l’hôpital, au patient, au traitement de sortie (y compris le type de modification par rapport aux médicaments pris avant l’admission) et à la gestion des médicaments au domicile. Un certain nombre d’éléments ont été exclus pour des raisons de non-utilité perçue par les pharmaciens, de confidentialité et de respect de la liberté de choix du patient. 2) Quarante-huit feuilles sur 71 données aux patients ont été reçues par les pharmaciens d’officine. Un quart des répondants a déclaré ne pas avoir utilisé la feuille, la raison majoritaire étant sa réception après la délivrance du traitement de sortie (n = 6/11). La majorité des pharmaciens d’officine a trouvé la plupart des informations utiles et la feuille de transfert bénéfique pour la continuité des soins. Une demande d’informations supplémentaires a été exprimée (comme la raison des changements de médicaments et de l’hospitalisation, etc.). 3) L’utilité, le bénéfice et les besoins d’informations supplémentaires par rapport aux informations de la feuille de transfert ont également été relevés par les 309 répondants de l’enquête nationale. La majorité des répondants a confirmé l’intérêt des différents éléments d’information de la feuille de transfert. Conclusion : La transmission d’une feuille de transfert contenant des informations sur le traitement médicamenteux à la sortie de l’hôpital présente un réel intérêt pour le pharmacien d’officine, car elles vont au-delà des informations retrouvées sur une prescription médicale. Néanmoins, la feuille de transfert devrait inclure davantage d’informations nécessaires pour la réalisation des soins pharmaceutiques

A review of the value of quadrivalent influenza vaccines and their potential contribution to influenza control

The contribution of influenza B to the seasonal influenza burden varies from year-to-year. Although 2 antigenically distinct influenza B virus lineages have co-circulated since 2001, trivalent influenza vaccines (TIVs) contain antigens from only one influenza B virus. B-mismatch or co-circulation of both B lineages results in increased morbidity and mortality attributable to the B lineage absent from the vaccine. Quadrivalent vaccines (QIVs) contain both influenza B lineages. We reviewed currently licensed QIVs and their value by focusing on the preventable disease burden. Modeling studies support that QIVs are expected to prevent more influenza cases, hospitalisations and deaths than TIVs, although estimates of the case numbers prevented vary according to local specificities. The value of QIVs is demonstrated by their capacity to broaden the immune response and reduce the likelihood of a B-mismatched season. Some health authorities have preferentially recommended QIVs over TIVs in their influenza prevention programmes

From meteorites to evolution and habitability of planets

The evolution of planets is driven by the composition, structure, and thermal state of their internal core, mantle, lithosphere, and crust, and by interactions with a possible ocean and/or atmosphere. A planet's history is a long chronology of events with possibly a sequence of apocalyptic events in which asteroids, comets and their meteorite offspring play an important role. Large meteorite impacts on the young Earth could have contributed to the conditions for life to appear, and similarly large meteorite impacts could also create the conditions to erase life or drastically decrease biodiversity on the surface of the planet. Meteorites also contain valuable information to understand the evolution of a planet through their gas inclusion, their composition, and their cosmogenic isotopes. This paper addresses the evolution of the terrestrial bodies of our Solar System, in particular through all phenomena related to meteorites and what we can learn from them. This includes our present understanding of planet formation, their interior, their atmosphere, and the effects and relations of meteorites with respect to these reservoirs. It brings further insight into the origin and sustainability of life on planets, including Earth. Particular attention is devoted to Earth and Mars, as well as to planets and satellites possessing an atmosphere (Earth, Mars, Venus, and Titan) or a subsurface ocean (e.g. Europa), because those are the best candidates for hosting life. Though the conditions on the planets Earth, Mars, and Venus were probably similar soon after their formation, their histories have diverged about 4 billion years ago. The search for traces of life on early Earth serves as a case study to refine techniques/environments allowing the detection of potential habitats and possible life on other planets. A strong emphasis is placed on impact processes, an obvious shaper of planetary evolution, and on meteorites that document early Solar System evolution and witness the geological processes taking place on other planetary bodies. © 2012 Elsevier Ltd. All rights reserved.SCOPUS: cp.jinfo:eu-repo/semantics/publishe

Superior antigen-specific CD4+ T-cell response with AS03-adjuvantation of a trivalent influenza vaccine in a randomised trial of adults aged 65 and older

BACKGROUND: The effectiveness of trivalent influenza vaccines may be reduced in older versus younger adults because of age-related immunosenescence. The use of an adjuvant in such a vaccine is one strategy that may combat immunosenescence, potentially by bolstering T-cell mediated responses. METHODS: This observer-blind study, conducted in the United States (US) and Spain during the 2008-2009 influenza season, evaluated the effect of Adjuvant System AS03 on specific T-cell responses to a seasonal trivalent influenza vaccine (TIV) in >/=65 year-old adults.Medically-stable adults aged >/=65 years were randomly allocated to receive a single dose of AS03-adjuvanted TIV (TIV/AS03) or TIV. Healthy adults aged 18-40 years received only TIV. Blood samples were collected on Day 0, Day 21, Day 42 and Day 180. Influenza-specific CD4+ T cells, defined by the induction of the immune markers CD40L, IL-2, IFN-gamma, or TNF-alpha, were measured in ex vivo cultures of antigen-stimulated peripheral blood mononuclear cells. RESULTS: A total of 192 adults were vaccinated: sixty nine and seventy three >/=65 year olds received TIV/AS03 and TIV, respectively; and fifty 18 - 40 year olds received TIV. In the >/=65 year-old group on Day 21, the frequency of CD4+ T cells specific to the three vaccine strains was superior in the TIV/AS03 recipients to the frequency in TIV (p /=65 year-old recipients of TIV/AS03 than in the 18 - 40 year old recipients of TIV on Days 21 (p = 0.006) and 42 (p = 0.011). CONCLUSION: This positive effect of AS03 Adjuvant System on the CD4+ T-cell response to influenza vaccine strains in older adults could confer benefit in protection against clinical influenza disease in this population. TRIAL REGISTRATION: (Clinicaltrials.gov.). NCT00765076

Assessment of an optimized manufacturing process for inactivated quadrivalent influenza vaccine: a phase III, randomized, double-blind, safety and immunogenicity study in children and adults

Abstract Background GSK has modified the licensed monovalent bulk manufacturing process for its split-virion inactivated quadrivalent influenza vaccine (IIV4) to harmonize the process among different strains, resulting in an increased number of finished vaccine doses, while compensating for the change from inactivated trivalent influenza vaccine (IIV3) to IIV4. To confirm the manufacturing changes do not alter the profile of the vaccine, a clinical trial was conducted to compare IIV4 made by the currently licensed process with a vaccine made by the new (investigational) process (IIV4-I). The main objectives were to compare the reactogenicity and safety of IIV4-I versus IIV4 in all age groups, and to demonstrate the non-inferiority of the hemagglutination-inhibition (HI) antibody responses based on the geometric mean titer ratio of IIV4-I versus IIV4 in children. Methods The Phase III, randomized, double-blind, multinational study included three cohorts: adults (18–49 years; N = 120), children (3–17 years; N = 821), and infants (6–35 months; N = 940). Eligible subjects in each cohort were randomized 1:1 to receive IIV4-I or IIV4. Both vaccines contained 15 μg of hemagglutinin antigen for each of the four seasonal virus strains. Adults and vaccine-primed children received one dose of vaccine, and vaccine-unprimed children received two doses of vaccine 28 days apart. All children aged ≥9 years were considered to be vaccine-primed and received one dose of vaccine. Results The primary immunogenicity objective of the study was met in demonstrating immunogenic non-inferiority of IIV4-I versus IIV4 in children. The IIV4-I was immunogenic against all four vaccine strains in each age cohort. The reactogenicity and safety profile of IIV4-I was similar to IIV4 in each age cohort, and there was no increase in the relative risk of fever (≥38 °C) with IIV4-I versus IIV4 within the 7-day post-vaccination period in infants (1.06; 95% Confidence Interval: 0.75, 1.50; p = 0.786). Conclusions The study demonstrated that in adults, children, and infants, the IIV4-I made using an investigational manufacturing process was immunogenic with a reactogenicity and safety profile that was similar to licensed IIV4. These results support that the investigational process used to manufacture IIV4-I is suitable to replace the current licensed process. Trial registration ClinicalTrials.gov: NCT02207413; trial registration date: August 4, 2014