Use of anti-infective drugs during pregnancy : prevalence, predictors of use and the risk of preterm birth and small-for-gestational-age newborns

Résumé: Les anti-infectieux sont parmi les médicaments les plus utilisés pendant la grossesse. Les indications pour l’utilisation de ces médicaments, telles que les infections bactériennes, figurent parmi les facteurs de risque les plus importants pour la prématurité et les enfants nés petits pour l'âge gestationnel («Small-for-gestational-age », SGA). Ces complications de la grossesse peuvent avoir des incidences sur la santé du nouveau né et sur son développement futur. Compte tenu des impacts sur la santé de la mère et de l’enfant, la prise en charge et le traitement efficace de ces infections sont impératifs. Cependant, l'utilisation des anti-infectieux, pour éviter des issues de grossesse défavorables, fait l’objet d’une controverse dans la littérature. Cette controverse est en partie liée à la qualité méthodologique discutable des études disponibles sur le sujet. Les quatre études présentées dans cette thèse ont donc pour objectif d’investiguer l’utilisation des anti-infectieux durant la grossesse ainsi que d’évaluer le risque de prématurité et de SGA après utilisation de ces médicaments en période gestationnelle. Une révision systématique de la littérature sur l’utilisation du métronidazole durant la grossesse est également présentée. Nous avons utilisé, comme source de données le Registre des Grossesses du Québec, une cohorte longitudinale conçue à partir du jumelage de trois bases de données administratives de la province du Québec (RAMQ, Med-Echo et ISQ). Le registre fournit des informations sur les prescriptions, les services pharmaceutiques et médicaux, ainsi que des donnés sur les soins d’hospitalisation de courte durée et démographiques. Les deux premières études présentées dans cette thèse ont eu pour objectif d’évaluer la prévalence, les tendances, les indications et les prédicteurs de l’utilisation des anti-infectieux dans une cohorte, extraite du registre, de 97 680 femmes enceintes. A l’aide d’un devis cas-témoins, les 2 dernières études ont mesuré l’association entre l’utilisation d’anti-infectieux durant les 2 derniers trimestres de grossesse et le risque de prématurité et de SGA, respectivement. Un cas de prématurité a été défini comme un accouchement survenu avant 37 semaines de gestation. Un cas de SGA a été défini comme l’accouchement d’un enfant dont le poids à la naissance se situe sous le 10ème percentile du poids normalisé à la naissance (compte tenu de l’âge gestationnel et du sexe du bébé). Les données ont été recueillies pour les agents systémiques oraux, ainsi que pour les classes et les agents individuels. Nos résultats ont montré que la prévalence de l’utilisation des anti-infectieux durant la grossesse était comparable à celle d’autres études déjà publiées (25%). Nous avons observé une augmentation de l’utilisation des agents plus anciens et ayant des profils d’innocuité connus. Les prédicteurs de l’usage en début de grossesse identifiés sont : avoir eu plus de deux différentes prescriptions (OR ajusté = 3,83, IC 95% : 3,3-4,3), avoir eu un diagnostic d’infection urinaire (OR= 1,50, IC 95% : 1,3-1,8) et un diagnostic d’infection respiratoire (OR= 1,40, IC 95% : 1,2-1,6). L’utilisation des macrolides a été associée à une diminution du risque de prématurité (OR =0,65, IC 95% : 0,50-0,85). En revanche, les femmes ayant été exposées au métronidazole ont vu leur risque augmenté de 80% (OR=1,81, IC 95% : 1,30-2,54). L’utilisation d’azithromycine a été associée à une diminution importante du risque chez les femmes ayant un diagnostic de rupture prématurée des membranes (OR=0,31, IC 95% : 0,10-0,93). Cependant, l'utilisation de sulfaméthoxazole-triméthoprime (SXT) a été significativement associée à une augmentation du risque de SGA (OR= 1,61, IC 95% : 1,16-2,23), tandis que celle des anti-infectieux urinaires a été associée à une diminution du risque (OR= 0,80, 95%CI : 0.65-0.97). Les conclusions de nos travaux suggèrent que l’utilisation des macrolides et des pénicillines diminuent le risque de prématurité et de SGA. Nous devons considérer l'utilisation de différents choix thérapeutiques tels que l’azithromycine, lors de la prise en charge des infections pouvant induire la prématurité et le SGA.

Bioprocess Technology for Antagonistic Pseudomonas MCCB 102, 103,Micrococcus MCCB 104, and Evaluation of Synechocystis MCCB 114, 115 as Probiotics for the Management of Vibrio in Shrimp Culture Systems

National Centre for Aquatic Animal Health, School of Environmental Studies, Cochin University of Science and Technology

Mangrove plant Ceriops tagal as a potential source of anti White Spot Syndrome Virus preparations for Penaeus monodon

White spot syndrome virus (WSSV) is the deadliest virus among crustaceans ever discovered having several unique and novel features. Recent developments in genomics and proteomics could elucidate the molecular process involved in the WSSV infection and the host pathogen interaction to some extent. Until now no fool proof treatment or prophylactic measure has been made available to control WSSV out breaks in culture system. Even though there are technologies like application of immunostimulants, vaccines, RNAi and several antiviral natural products none of them has been taken to the level of clinical trials. However, there are several management options such as application of bioremediation technologies to maintain the required environmental quality, maintenance of zero water exchange systems coupled with application of probiotics and vaccines which on adoption shall pave way for successful crops amidst the rapid spread of the virus. In this context the present work was undertaken to develop a drug from mangrove plants for protecting shrimp from WSSV.Mangroves belong to those ecosystems that are presently under the threat of destruction, diversion and blatant attack in the name of so called ‘developmental activities’. Mangrove plants have unique ecological features as it serves as an ecotone between marine and terrestrial ecosystem and hence possess diversity of metabolites with diverse activities. This prompted them being used as remedial measures for several ailments for ages. Among the mangrove plants Ceriops tagal, belonging to the family Rhizophororaceae was in attention for many years for isolating new metabolites such as triterpenes, phenolic compounds, etc. Even though there were attempts to study various plant extracts to develop anti-viral preparations their activity against WSSV was not investigated as yet.

Two isoforms of anti-lipopolysaccharide factors identified and characterized from the hemocytes of portunid crabs, Portunus pelagicus and Scylla tranquebarica

Anti-lipopolysaccharide factors (ALFs), a type of cationic antimicrobial peptides (AMPs), and their derivatives are becoming predominant candidates for potential drugs in viral and bacterial diseases. This study reports the first ALF from the mud crab Scylla tranquebarica (StALF, JQ899453) and the second ALF isoform from the blue swimmer crab Portunus pelagicus (PpALF2, JQ899452). Both sequences encoded for precursor molecules, starting with a signal peptide containing 26 amino acid residues, followed by a highly cationic mature peptide, containing two conserved cysteine residues flanking a putative lipopolysaccharide (LPS)-binding domain. BLAST analysis revealed that both PpALF2 and StALF exhibited significant similarity with crustacean ALF sequences. The predicted molecular mass of the mature ALFs was 11.2 kDa with an estimated pI of 10.0. PpALF2 and StALF also showed the typical pattern of alternating hydrophobic and hydrophilic residues in their putative disulphide loop, suggesting that they comprise the same functional domain. Phylogenetic analysis showed that PpALF2 and StALF have similar evolutionary status and they were phylogenetically ancient immune effector molecules which may play an essential role in the host defense mechanism. The spatial structures of PpALF2 and StALF possessed four beta-strands and two alpha-helices. The results indicated that there were more than one ALF involved in crab immunity against various pathogens. ALFs would provide candidate promising therapeutic or prophylactic agents in health management and diseases control in crustacean aquaculture

Importância do alinhamento entre os valores pessoais e valores organizacionais no comprometimento organizacional : estudo de caso

O presente estudo investiga o impacto do alinhamento dos valores pessoais com os organizacionais no comprometimento organizacional, através de um estudo de caso realizado no sector da cerâmica estrutural. A metodologia de investigação consiste na aplicação de um questionário a uma amostra de 148 colaboradores de uma empresa. A análise do alinhamento dos valores pessoais e organizacionais é feita com base no modelo Triaxial dos 3Es dos valores e no modelo dos Três Componentes do Comprometimento Organizacional. Os resultados revelam a existência de alinhamento parcial entre os valores pessoais e os organizacionais, com congruência apenas na dimensão dos valores ético-sociais. Não se observaram correlações significativas entre o alinhamento dos valores pessoais e os organizacionais percepcionados e o comprometimento organizacional dos colaboradores. Conclui-se, pois, pela importância dos valores pessoais e organizacionais como uma importante variável nos estudos do comprometimento organizacional a desenvolver a nível nacional.

Avaliação de riscos e desenvolvimento de equipamento anti-queda para acesso vertical a espaços confinados

Na fábrica da EPAL, em Vale da Pedra, o risco de queda em altura no acesso vertical a espaços confinados, foi avaliado como sendo aceitável mediante a adoção de medidas de controlo que não existiam, ou que não eram adequadas, ou ainda que não eram utilizadas. Para responder a este problema, foi concebido, desenvolvido e ensaiado um inovador dispositivo portátil anti-queda. Este previne a queda no acesso entre o pavimento e os primeiros degraus de aberturas verticais conducentes a espaços confinados. Além da função preventiva, também pode fazer parte da proteção anti-queda, como ponto de ancoragem dos equipamentos de proteção contra quedas. Os ensaios realizados revelaram que, em comparação com as alternativas pré-fabricadas disponíveis, esta solução é mais adequada para prevenir quedas, por se adaptar a múltiplas configurações de acesso, com um dispositivo relativamente leve, fácil de transportar e de aplicar, estável e resistente. / In EPAL factory in Vale da Pedra, the risk of falling from a height in the vertical access to confined spaces, was evaluated as being acceptable by the adoption of control measures that did not exist, or were not suitable, or were not used. To respond to this problem, an innovative portable anti-falling device was designed, developed and tested. This prevents falling in access between the ground and the first steps of vertical openings leading to confined spaces. In addition to the preventive function, it can also be part of the fall-arrest protection, as anchor point of fall protection equipment. The tests revealed that, in comparison with the prefabricated alternatives available, this solution is best suited to prevent falls, due to its adaptability to multiple access settings, with a relatively light device, easy to carry and to use, stable and resistant.

An in vitro assessment of the effects of broad-spectrum antibiotics on the human gut microflora and concomitant isolation of a Lactobacillus plantarum with anti-Candida activities

Chemostat culture was used to determine the effects of the antimicrobial agents tetracycline and nystatin on predominant components of the human gut microflora. Their addition to mixed culture systems caused a non-specific, and variable, decrease in microbial populations, although tetracycline allowed an increase in numbers of yeasts. Both had a profound inhibitory effect upon populations seen as important for gut health (bifidobacteria, lactobacilli). However, a tetracycline resistant Lactobacillus was enriched from the experiments. A combination of genotypic and phenotypic characterisations confirmed its identity as Lactobacillus plantarum. This strain exerted powerful inhibitory effects against Candida albicans. Because of its ability to resist the effects of tetracycline, this organism may be useful as a probiotic for the improved management of yeast related conditions such as thrush and irritable bowel syndrome. (C) 2004 Elsevier Ltd. All rights reserved.

Protocol for the PINCER trial: a cluster randomised trial comparing the effectiveness of a pharmacist-led IT-based intervention with simple feedback in reducing rates of clinically important errors in medicines management in general practices

Background: Medication errors are an important cause of morbidity and mortality in primary care. The aims of this study are to determine the effectiveness, cost effectiveness and acceptability of a pharmacist-led information-technology-based complex intervention compared with simple feedback in reducing proportions of patients at risk from potentially hazardous prescribing and medicines management in general (family) practice. Methods: Research subject group: "At-risk" patients registered with computerised general practices in two geographical regions in England. Design: Parallel group pragmatic cluster randomised trial. Interventions: Practices will be randomised to either: (i) Computer-generated feedback; or (ii) Pharmacist-led intervention comprising of computer-generated feedback, educational outreach and dedicated support. Primary outcome measures: The proportion of patients in each practice at six and 12 months post intervention: - with a computer-recorded history of peptic ulcer being prescribed non-selective non-steroidal anti-inflammatory drugs - with a computer-recorded diagnosis of asthma being prescribed beta-blockers - aged 75 years and older receiving long-term prescriptions for angiotensin converting enzyme inhibitors or loop diuretics without a recorded assessment of renal function and electrolytes in the preceding 15 months. Secondary outcome measures; These relate to a number of other examples of potentially hazardous prescribing and medicines management. Economic analysis: An economic evaluation will be done of the cost per error avoided, from the perspective of the UK National Health Service (NHS), comparing the pharmacist-led intervention with simple feedback. Qualitative analysis: A qualitative study will be conducted to explore the views and experiences of health care professionals and NHS managers concerning the interventions, and investigate possible reasons why the interventions prove effective, or conversely prove ineffective. Sample size: 34 practices in each of the two treatment arms would provide at least 80% power (two-tailed alpha of 0.05) to demonstrate a 50% reduction in error rates for each of the three primary outcome measures in the pharmacist-led intervention arm compared with a 11% reduction in the simple feedback arm. Discussion: At the time of submission of this article, 72 general practices have been recruited (36 in each arm of the trial) and the interventions have been delivered. Analysis has not yet been undertaken.

Spatio-temporal variation in predation by urban domestic cats (Felis catus) and the acceptability of possible management actions in the UK

Urban domestic cat (Felis catus) populations can attain exceedingly high densities and are not limited by natural prey availability. This has generated concerns that they may negatively affect prey populations, leading to calls for management. We enlisted cat-owners to record prey returned home to estimate patterns of predation by free-roaming pets in different localities within the town of Reading, UK and questionnaire surveys were used to quantify attitudes to different possible management strategies. Prey return rates were highly variable: only 20% of cats returned ≥4 dead prey annually. Consequently, approximately 65% of owners received no prey in a given season, but this declined to 22% after eight seasons. The estimated mean predation rate was 18.3 prey cat−1 year−1 but this varied markedly both spatially and temporally: per capita predation rates declined with increasing cat density. Comparisons with estimates of the density of six common bird prey species indicated that cats killed numbers equivalent to adult density on c. 39% of occasions. Population modeling studies suggest that such predation rates could significantly reduce the size of local bird populations for common urban species. Conversely, most urban residents did not consider cat predation to be a significant problem. Collar-mounted anti-predation devices were the only management action acceptable to the majority of urban residents (65%), but were less acceptable to cat-owners because of perceived risks to their pets; only 24% of cats were fitted with such devices. Overall, cat predation did appear to be of sufficient magnitude to affect some prey populations, although further investigation of some key aspects of cat predation is warranted. Management of the predation behavior of urban cat populations in the UK is likely to be challenging and achieving this would require considerable engagement with cat owners.

Mapping evidence gaps in anti-corruption: assessing the state of the operationally relevant evidence on donors' actions and approaches to reducing corruption

This paper charts the current evidence on effectiveness of different anti-corruption reforms, and identifies significant evidence gaps. Despite a substantial amount of literature on corruption, this review found very few studies focusing on anti-corruption reforms, and even fewer that credibly assess issues of effectiveness and impact. The evidence was strong for only two types of interventions: public financial management (PFM) reforms and supreme audit institutions (SAIs). For PFM, the evidence in general showed positive results, whereas the effectiveness was mixed for SAIs. No strong evidence indicates that any of the interventions pursued have been ineffective, but there is fair evidence that anti-corruption authorities, civil service reforms and the use of corruption conditionality in aid allocation decisions in general have not been effective. The paper advocates more operationally-relevant research and rigorous evaluations to build up the missing evidence base, particularly in conflict-afflicted states, in regards to the private sector, and on the interactions and interdependencies between different anti-corruption interventions.

Fungicide-resistance management tactics: impacts on Zymoseptoria tritici populations

Azoles and Succinate Dehydrogenase Inhibitors (SDHIs) are the main fungicides available for septoria tritici blotch control, causal agent Zymoseptoria tritici. Decline in azole sensitivity, in combination with European legislation, poses a threat to wheat production in Ireland. Azole fungicides select CYP51 mutations differentially; it was hypothesised that using combinations of azoles could be an effective anti-resistance tool. Naturally inoculated field experiments were carried out in order to understand the impacts of using combinations of azoles, epoxiconazole and metconazole, on azole sensitivity. Approximately 3700 isolates were isolated and their sensitivity to both azoles analysed. Findings showed that limiting the number of applications, by alternating each fungicide, slowed selection for reduced azole sensitivity. Limiting azole use by reducing doses did not reduce selection for decreased azole sensitivity. Although not complete, cross-resistance was observed between the two azoles, which will lead to general reduction in azole sensitivity. A sub-selection of isolates from each treatment at each location were analysed for changes in the CYP51 gene. Sequence analysis identified 49 combinations of mutations in the CYP51 gene, and three different inserts in the CYP51 promoter. Intragenic recombination also featured in these populations. Baseline studies of five new SDHIs were carried out on 209 naturally infected, non-SDHI-treated isolates. With the exception of fluopyram, cross-resistance was apparent between the SDHIs. Analysis of 2300 isolates found that when compared to the solo products, mixing the SDHI isopyrazam and the azole epoxiconazole increased epoxiconazole sensitivity, but had no apparent effect on isopyrazam sensitivity. SDHI resistance-conferring mutations were absent in the baseline and experimental isolates. As long as azoles are used, Z. tritici populations will continue to evolve towards resistance. Combining different modes-of-action, SDHIs and multi-sites, with azoles will relieve some of that selective pressure. To get the best out of available fungicides, they should be used in combination with host resistance and good crop management practices.

Desenvolvimento de um modelo de intervenção baseado no sistema toyota de produção e na teoria das restrições : autilização da pesquisa-ação em uma indústria de cerâmica vermelha de pequeno porte da região metropolitana de Porto Alegre

As teorias de gestão da produção, como o Sistema Toyota de Produção e a Teoria das Restrições, têm apresentado resultados positivos, em realidades organizacionais muito diferenciadas. Contudo, é preciso garantir a efetividade das ações em provocar as mudanças desejadas. Neste sentido, métodos de pesquisa participativa, como a pesquisaação, promovem a participação e o comprometimento das pessoas implicadas no processo de mudança. Esta dissertação propõe a construção de um modelo de intervenção visando aumentar a competitividade de uma realidade organizacional específica. Foram utilizados a pesquisa-ação, como método de trabalho e a Teoria das Restrições (TOC) e o Sistema Toyota de Produção (STP), como embasamento teórico. Cabe ressaltar que este modelo foi construído a partir de uma intervenção realizada em uma indústria de cerâmica vermelha da região metropolitana de Porto Alegre. Assim, a presente dissertação foi organizada da seguinte maneira: revisão bibliográfica do método de condução da pesquisa e adaptação do mesmo para o presente trabalho, fundamentação teórica, composta pelos princípios básicos de sustentação do STP e da TOC, análise do contexto do segmento industrial em questão, descrição da intervenção realizada e apresentação do modelo construído, análise dos resultados finais, conclusões e recomendações para futuras pesquisas. A análise dos resultados obtidos e as conclusões do estudo revelam a possibilidade de generalização parcial do modelo proposto, desde que observadas as características específicas da realidade industrial em questão.

Novas configurações organizacionais: pesquisa exploratória empírica sobre organizações locais

Esta pesquisa investiga a questão da evolução das configurações organizacionais. As mudanças ocorridas no ambiente competitivo brasileiro nos últimos anos levaram muitas empresas a buscar novos modelos de organização e gestão. Tal movimento pode representar uma superação, ou alternativamente uma evolução, do paradigma taylorista-fordista em direção a formatos mais orgânicos. Este projeto compreende uma pesquisa bibliográfica sobre o tema e uma pesquisa exploratória de campo, envolvendo organizações locais. São discutidos padrões genéricos de mudança e tendências, estabelecendo-se proposições a serem avaliadas em trabalho posterior.