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.

Keeping cool in acute liver failure: rationale for the use of mild hypothermia.

Encephalopathy, brain edema and intracranial hypertension are neurological complications responsible for substantial morbidity/mortality in patients with acute liver failure (ALF), where, aside from liver transplantation, there is currently a paucity of effective therapies. Mirroring its cerebro-protective effects in other clinical conditions, the induction of mild hypothermia may provide a potential therapeutic approach to the management of ALF. A solid mechanistic rationale for the use of mild hypothermia is provided by clinical and experimental studies showing its beneficial effects in relation to many of the key factors that determine the development of brain edema and intracranial hypertension in ALF, namely the delivery of ammonia to the brain, the disturbances of brain organic osmolytes and brain extracellular amino acids, cerebro-vascular haemodynamics, brain glucose metabolism, inflammation, subclinical seizure activity and alterations of gene expression. Initial uncontrolled clinical studies of mild hypothermia in patients with ALF suggest that it is an effective, feasible and safe approach. Randomized controlled clinical trials are now needed to adequately assess its efficacy, safety, clinical impact on global outcomes and to provide the guidelines for its use in ALF.

Use of corticosteroid therapy on the modulation of uterine inflammatory response in mares after artificial insemination with frozen semen

In order to modulate uterine inflammatory response and evaluate the effect of corticosteroid therapy on fertility, 90 cycles of 45 mares were used for artificial insemination with frozen semen, using three different protocols: G1 - inseminated with frozen semen (800 x 10(6) viable spermatozoa pre-freezing) + 20 mL of seminal plasma; G2 - inseminated with frozen semen (800 x 10(6) viable spermatozoa pre-freezing) + corticosteroid therapy; G3 - inseminated with frozen semen (800 x 10(6) viable spermatozoa pre-freezing) + 20 mL of seminal plasma + corticosteroid therapy. Corticosteroid therapy consisted on one administration of prednisolone acetate (0.1 mg/Kg - Predef (R)) when mares presented 35mm follicles and uterine edema, concomitantly with the unique dose of hCG (human chorionic gonadotropin), then repeated each 12 hours until ovulation. on first fertility trial, with normal mares, there was no difference between control and treated groups (p>0.05), using seminal plasma associated with corticosteroid therapy (40 vs. 38%, respectively) or corticosteroid therapy alone (40 vs. 45% respectively). The second fertility trial, performed with mares with previous history of post-insemination endometritis, demonstrated a significant increase of pregnancy rate when mares were submitted to corticosteroid therapy (0.0 vs. 64.5%, respectively; p<0.05). Corticosteroid therapy was shown to be safe, with no physical or reproductive alterations on treated mares, demonstrating to be an adequate option to those animals with history of post-breeding or post-insemination endometritis. Further clinical research is necessary to confirm these results and contribute to the establishment of preventive therapy for cases of post-insemination endometritis.

Use of Adipose Tissue-Derived Mesenchymal Stem Cells for Experimental Tendinitis Therapy in Equines

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Urinary fluoride output in children following the use of a dual-fluoride varnish formulation

Objective: This study evaluated the bioavailability of fluoride after topical application of a dual-fluoride varnish commercially available in Brazil, when compared to Duraphat T. Material and methods: The urinary fluoride output was evaluated in seven 5-year-old children after application of the fluoride varnishes, in two different phases. In the first phase (I), children received topical application of the fluoride varnish Duofluorid XII (2.92% fluorine, calcium fluoride + 2.71% fluorine, sodium fluoride, FGM (TM)). After 1-month interval (phase II), the same amount (0.2 mL) of the fluoride varnish Duraphat (2.26% fluorine, sodium fluoride, Colgate T) was applied. Before each application all the volunteers brushed their teeth with placebo dentifrice for 7 days. Urinary collections were carried out 24 h prior up to 48 h after the applications. Fluoride intake from the diet was also estimated. Fluoride concentration in diet samples and urine was analyzed with the fluoride ion-specific electrode and a miniature calomel reference electrode coupled to a potentiometer. Data were tested by ANOVA and Tukey's post hoc test (p < 0.05). Results: There were significant differences in the urinary fluoride output between phases I and II. The use of Duofluorid XII did not significantly increase the urinary fluoride output, when compared to baseline levels. The application of Duraphat caused a transitory increase in the urinary fluoride output, returning to baseline levels 48 h after its use. Conclusions: The tested varnish formulation, which has been shown to be effective in in vitro studies, also can be considered safe.

Use of Medicines Among a Brazilian Elderly Sample: A Cross-sectional Study

Background: The use of multiple medicines is very frequent among the elderly, allowing them to perceive more often adverse side effects from drugs and present undesirable drug interactions.Methods: This article presents a cross-sectional survey about the use of medicines among 300 elderly Brazilians, equally divided into institutionalized and community-dwelling groups.Results: The average daily intake of medicines is 3.2 among institutionalized elderly, a higher (p < 0.001) number when compared with community-dwelling elderly, who takes an average of 1.8 medicines daily. The most commonly used medications are antihypertensives (58.0%), diuretics (23.0%), nonsteroidal anti-inflammatory drugs (22.7%), supplements (21.7%), antidiabetics (16.3%), and antiulcerants (14.0%). Antiulcerants, diuretics, supplements, and central nervous system drugs are more frequently used by institutionalized than by community-dwelling elderly.Conclusion: In this Brazilian elderly sample, the most widely used medicines were antihypertensives, diuretics, and nonsteroidal anti-inflammatory drugs, and institutionalized used more medications than community-dwelling elderly. Copyright (C) 2011, Taiwan Society of Geriatric Emergency & Critical Care Medicine. Published by Elsevier Taiwan LLC. All rights reserved.

Behavioral and biological correlates of medicine use in type 2 diabetic patients attended by Brazilian public healthcare system

A relação entre atividade física e consumo de medicamentos não é clara. Assim, o objetivo do estudo foi investigar a relação entre nível de atividade física e uso de medicamentosem diabéticos tipo 2 atendidos pelo Sistema Único de Saúde. A amostra foi composta por 121 diabéticos do tipo 2 de ambos os sexos atendidos pelos sistema público de saúde. Gordura corporal (antropometria e bioimpedância elétrica), atividade física (Questionário de Baecke) e uso de medicamentos (15 dias prévios a avaliação) foram avaliados. Houve relação entre uso de medicamentos e sexo (r = 0.18; p = 0.045), índice de massa corporal (r = 0.22; p = 0.012), circunferência de cintura (r = 0.19; p = 0.029), percentual de gordura (r = 0.21; p = 0.016), idade (r = 0.23; p = 0.009) e atividade física (r = -0.22; p = 0.012). A regressão linear incluiu no modelo apenas idade (β = 0.718; p = 0.057), IMC BMI (β = 0.057; p = 0.022) e atividade física (β = -0.176; p = 0.044) no modelo multivariado. Conclui-se que a prática de atividade física diminui uso de medicamentos independente da idade e obesidade.

Investigation into the use of the Laryngeal Mask Airway in pentobarbital anesthetized dogs

Objective - To investigate the use of the laryngeal mask airway (LMA) in dogs. Study Design - Prospective experimental study. Animals - Eight healthy adult mixed breed dogs weighing from 15 to 20 kg. Methods - The dogs were anesthetized with intravenous pentobarbital. An LMA was introduced after the induction of anesthesia and 1 L/min O2 plus 1 L/min air was delivered using a circle anesthetic system. Respiratory rate, tidal volume, arterial O2 saturation (pulse oximetry), end tidal CO2, inspired fraction of O2, pulse rate, and mean arterial blood pressure were measured after the insertion of the LMA and 30, 60, 90, and 120 minutes afterwards. Results - There were no changes in respiratory rate, tidal volume, arterial O2 saturation, and pulse rate during anesthesia. End tidal CO2 decreased significantly by the end of anesthesia and ventilation appeared satisfactory. Conclusions - An LMA appeared to be an alternative option to maintain the patency of the airway in dogs. Clinical Relevance - This device may allow safe maintenance of an airway in dogs when intubation is difficult or when it interferes with the procedure (eg, cervical myelography). ©Copyright 1999 by The American College of Veterinary Surgeons.

A randomized and controlled trial about the use of oral isotretinoin for photoaging

Topical retinoids are used to treat photoaging; oral isotretinoin is gold standard for acne; off label indications, including photoaging, have been reported with insufficient evidence of efficacy. This is a randomized controlled phase II trial with clinical and histological assessment to evaluate efficacy and safety of oral isotretinoin for photoaging. Study population was comprised of 32 menopausal or sterilized women, aged 40-55, divided in 2 groups: A (21) received 20mg isotretinoin, 3 times per week, nightly moisturizer, and daily sunscreen, for three months; B (11) just moisturizer/sunscreen. Main outcome measures were: overall clinical assessment; profilometry, corneometer and elasticity tests in periocular regions and left forearm; before/after biopsies from left forearm in patients of B and in 10 randomly selected of A. Microscopic blinded evaluation of epidermal thickness, dermal elastosis, new collagen, p53 epidermal expression was performed by quantitative digital image analysis. All data were submitted to statistical analysis. Clinical evaluation showed slight improvement; profilometry, corneometer and skin elasticity tests presented significant difference in pre/post values (P = 0.001 to 0.028), but no differences between A/B. Histological findings and p53 expression were comparable between groups before treatment (P > 0.1); microscopic analysis showed no differences between groups for most variables, after treatment. Slight but significant difference between A/B for p53 with major reduction post isotretinoin [0.66±0.31 vs. 0.94±0.34 respectively (P = 0.04) was observed. There were minor side effects and no significant laboratory test alterations. We concluded that no significant clinical, microscopic changes but p53 epidermal expression reduction were observed. The role of ultra-violet induced p53 mutation in skin carcinogenesis reinforces retinoids chemoprevention. Oral isotretinoin seemed safe but not effective to treat photoaging. Caution should be considered for women prone to pregnancy. Further controlled studies are necessary. © 2010 The International Society of Dermatology.

Effective Use of Alteplase for Occluded Tunneled Venous Catheter in Hemodialysis Patients

Despite their propensity for significant infectious and mechanical complications, tunneled central venous catheters (CVCs) have become a common means of vascular access in the world for patients requiring chronic hemodialysis for end-stage renal disease. The objective of this study was to explore if cryopreserved solutions of the thrombolytic agent alteplase could be used as an effective, safe, and economically reasonable alternative in hemodialysis patients with occluded tunneled CVC. Patients requiring chronic hemodialysis and presenting with occluded tunneled CVC received a sufficient volume of the alteplase solution to fill the occluded catheter. To make alteplase economically feasible, it was diluted to 1-mg/mL aliquots and they were stored at -20 degrees C until use. Eighty-one patients accounting for 179 attempted clearances were assessable for efficacy. One hundred forty-seven (82.1%) of the 179 catheter clearance attempts resulted in successful catheter clearance after one dose. Twenty-seven (15.1%) of all occluded CVCs were successful after two doses whereas five (2.8%) were not. No adverse events were reported. Cryopreserved 1-mg/mL aliquots of alteplase are safe and effective in the clearance of occluded CVC for hemodialysis patients.

Use of nanoparticulate zinc oxide as intracanal medication in endodontics: pH and antimicrobial activity

The aim of this study was to evaluate the pH and antimicrobial activity of micro or nanoparticulate zinc oxide (ZnO) pastes with or without calcium hydroxide (CH). The following medications were evaluated: microparticulate ZnO + polyethylene glycol (PEG) 400; nanoparticulate ZnO + PEG 400; PEG 400; CH + microparticulate ZnO + PEG 400 and CH + nanoparticulate ZnO + PEG 400. The pH was assessed between 12 hours and 28 days, using a digital pH meter. The antimicrobial activity against Enterococcus faecalis (ATCC-9212), Candida albicans (ATCC-10231), Pseudomonas aeruginosa (ATCC-27853), Staphylococcus aureus (ATCC-6538) and Kocuria rhizophila (ATCC-9341) was determined in triplicate using agar diffusion test. The results were submitted to Kruskal-Wallis/Dunn and ANOVA/Tukey tests with 5% significance. The highest pH values were found for CH+ZnO, with higher values for nanoparticulate ZnO after 12 hours and 21 days (p<0.05). CH+ZnO medication promoted higher growth inhibition against P. aeruginosa and lower against E. faecalis. Calcium hydroxide pastes have higher pH and antimicrobial activity when associated with either micro- or nanoparticulate zinc oxide.

Taste alteration, mouth dryness and teeth staining as side effects of medications taken by elderly

Elderly patients generally use several types of medication, some of which may cause oral side effects. Aim: To investigate the oral side effects caused by medication in an elderly sample. Methods: Three hundred patients were interviewed about their use of medication and were divided in two groups: institutionalized (n=150) and community-dwelling (n=150) elderly. Results: The most used drugs were antihypertensives (53%) for community-dwelling elders and antiulceratives (76%) for the institutionalized ones. The more prevalent side effects were taste alterations that occurred in 19%, dry mouth in 17% and teeth staining in 2%. Conclusions: A high prevalence of oral side effects from medications used by the elderly was found in this study. The health professionals should be aware of the possible side effects caused by prescribed medications.

Potential use of bioagents in the control of postharvest rot in melon

Rot caused by Fusarium pallidoroseum has had a severely negative impact on the export of melons from Brazil. Uncertainty regarding the health of the fruit due to the quiescent infection of the pathogen has led producers to use fungicides in the postharvest treatment of the fruit, thereby causing contamination and risking the health of consumers. Consequently, there is a demand for clean and safe natural technologies for the postharvest treatment of melons, including biological control. The present study aimed at evaluating bioagents for use in controlling Fusarium rot in 'Galia'melon. The following bioagents were evaluated: two isolates of Bacillus subtilis, B. licheniformis and a mixture of B. subtilis and B. licheniformis, as well as the yeasts Sporidiobolus pararoseus, Pichia spp., Pichia membranifaciens, P. guilliermondii, Sporobolomyces roseus, Debaryomyces hansenii and Rhodotorula mucilagenosa. Treatment with imazalil and water were used as controls. Two experiments were conducted in a completely randomised design with 10 replicates per treatment with four fruit per replicate; the disease incidence was evaluated in the first experiment, and the disease severity was evaluated in the second. Similarity analysis of the temporal evolution profiles of rot incidence caused by F. pallidoroseum allowed the evaluated treatments to be clustered into four groups. In the first experiment, the yeasts P. membranifaciens and D. hansenii produced results similar to that of the fungicide imazalil. The second experiment highlighted the yeasts P. guilliermondii and R. mucilaginosa. Electron microscopy studies confirmed that once applied to the fruit, the yeasts colonised the skin and damaged the pathogen mycelium; the action of the yeasts affected the mycelium of F. pallidoroseum, which had infected wounds on the fruit's surface. Bacillus spp. did not provide good disease control. These results demonstrated that yeasts have the potential to control postharvest rot caused by F. pallidoroseum in 'Galia'melon.

Evaluation of the use of probiotic acid lactic bacteria in the development of chicken hambúrguer

The objective of this study was to investigate the effect of fermentation with Lactobacillus acidophilus CRL 1014 on the physicochemical, microbiological and sensory characteristics of a hamburger product like processed with chicken meat and okara flour, with reduction of curing salts. A mixture of ingredients containing 90% chicken meat and 10% okara flour was subjected to the following treatments: F1: fermented with Lactobacillus acidophilus; F2:75 mg nitrite/kg and fermented with Lactobacillus acidophilus; F3: 150 mg nitrite/kg and unfermented. The quality of the “hamburgers” was assessed by physical and chemical analysis (pH, cooking yield and shrinkage), chemical composition, microbiological tests (Salmonella spp., count of sulphite-reducing clostridia, staphylococos coagulase-positive, total coliforms and Escherichia coli) and sensory analysis (sensory acceptance and purchase intent). During the first six days of fermentation, there was a decrease in pH from approximately 6.33 to 5.10. All the samples showed the same chemical composition (p < 0.05). The fermentation process was observed to inhibit the multiplication of microorganisms of several groups: coagulasepositive staphylococci, sulphite-reducing clostridia, Salmonella spp. and E. coli. The different “hamburgers” formulations showed high scores for all the sensory attributes evaluated, without differing from each other (p < 0.05). The results showed that the use of L. acidophilus CRL 1014 enabled the production of a safe product, with good physicochemical and sensory characteristics, in the absence of curing salts.

The use of soybean integrated pest management in Brazil: a review

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)