Randomized controlled trial of probiotics for the prevention of spontaneous preterm delivery associated with intrauterine infection: study protocol

Background: Spontaneous preterm deliveries that occur before the 34th week of gestation, and particularly before the 32nd week of gestation, have been strongly associated to intrauterine infection, ascending from vagina, and represent the largest portion of neonatal deaths and neurological problems. Bacterial vaginosis, characterized by a diminished or absent flora of lactobacilli and increased colonization of several anaerobic or facultative microorganisms, increases two times the risk of preterm delivery before the 34th week. Trials of antibiotics failed to show efficacy and effectiveness against spontaneous preterm birth related to bacterial vaginosis. Some studies indicate benefit from selected probiotics to treat genitourinary infections, including bacterial vaginosis. Objective: The purpose of this study is to evaluate the effectiveness of the early administration of selected probiotics to pregnant women with asymptomatic bacterial vaginosis/intermediate degree infection to reduce the occurrence of spontaneous preterm delivery and related neonatal mortality and morbidity. Methods/Design: Women attending public prenatal care services in Rio de Janeiro will be screened to select asymptomatic pregnant women, less than 20 weeks' gestation, with no indication of elective preterm delivery. Those with vaginal pH > = 4.5 and a Nugent score between 4 and 10 (intermediate degree infection or bacterial vaginosis) will be randomized to either the placebo or the intervention group, after written informed consent. Intervention consists in the use of probiotics, Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14, 2 capsules a day, each capsule containing more than one million bacilli of each strain, for 6-12 weeks, up to the 24th-25th wk of gestation. Ancillary analyses include quantification of selected cervicovaginal cytokines and genotyping of selected polymorphisms. The randomization process is stratified for history of preterm delivery and blocked. Allocation concealment was designed as well as blinding of women, caregivers and outcome evaluators. The study will be supervised by an independent monitoring committee. Outcomes under study are preterm delivery (< 34- < 32 weeks of gestation) and associated neonatal complications: early neonatal sepsis, bronchopulmonary dysplasia, periventricular leukomalacia, necrotizing enterocolitis, and prematurity-related retinopathy; definitions were adapted from those recommended by the 2002 version of the Vermont-Oxford Network. Trial registration at NIH register: NCT00303082

A randomised controlled trial of probiotics for the prevention of spontaneous preterm delivery associated with bacterial vaginosis: preliminary results

BACKGROUND: Bacterial vaginosis increases the risk of spontaneous preterm delivery at less than 34 weeks of gestation. OBJECTIVE: The purpose of this study was to evaluate the efficacy of the early administration of selected lactobacilli strains (probiotics) to pregnant women with asymptomatic bacterial vaginosis/intermediate-degree infections to prevent spontaneous premature delivery and associated neonatal morbidity. METHODS/DESIGN: Asymptomatic pregnant women at less than 20 weeks of gestation, with no indication of elective preterm delivery, with a vaginal pH ??? 4.5 and Nugent score > 3 were randomly assigned to the placebo or intervention group (oral administration of selected lactobacilli up to the 24th to 26th week of gestation). The randomisation was stratified for the history of premature delivery (HPD) and blocked. The allocation was concealed, and the participating health professionals and patients were blinded. The primary outcome was preterm delivery (<34 to <32 weeks), and the secondary outcomes were associated neonatal complications. RESULTS: In total, 4,204 pregnant women were screened; 320 and 324 individuals were respectively randomly assigned to the placebo and intervention groups, and 62% finished the trial. None of the randomised patients were lost to follow-up. For the non-HPD stratum, the intent-to-treat relative risks of spontaneous premature birth at < 34 and < 37 weeks' gestation were 0.33 (0.03, 3.16) and 0.49 (0.17, 1.44), respectively, and they were non-significant (ns) with p = 0.31 and 0.14. The corresponding actual treatment figures were zero and 0.32 (0.09, 1.19), which were ns with p = 0.12 and 0.06. The intent-to-treat relative risk of spontaneous premature birth at < 37 weeks of gestation for the trial as a whole, including HPD and non-HPD participants, was 0.69 (0.26, 1.78), p = 0.30 (ns). The neonatal complications under evaluation occurred in only one infant (< 34 weeks; placebo group) who presented with respiratory distress syndrome and suspected early neonatal sepsis. The recorded adverse events were minor and relatively non-specific. CONCLUSIONS: The efficacy of the tested probiotics to prevent preterm delivery among women without a history of preterm delivery was not determined because the study sample was insufficient to estimate statistically significant intent-to-treat effects; additional studies are needed to evaluate this intervention among these women

Avaliação tecnológica em saúde: densitometria óssea e terapêuticas alternativas na osteoporose pós-menopausa Technology assessment in health care: bone densitometry and alternatives therapeutical in post-menopausal osteoporosis

Este artigo apresenta de forma sucinta os fatores considerados e as metodologias de síntese empregadas em uma avaliação tecnológica, assim como a lógica subjacente à sua elaboração e utilização no campo da saúde pública. O exemplo utilizado focaliza o problema osteoporose na pós-menopausa, analisando a oportunidade da difusão, no momento atual, da densitometria óssea e de tecnologias antiosteoporose em nosso país. Os estudos disponíveis sobre os efeitos das tecnologias envolvidas foram revisados, seguindo a metodologia recomendada, a fim de produzir uma síntese das evidências científicas, atualizada e aplicada ao nosso país. Análises de custo-efetividade preliminares de alternativas de intervenção, frente à assistência tradicional, são apresentadas, considerando mulheres na perimenopausa e com 65 anos de idade. A despeito das hipóteses otimistas assumidas, as estimativas de custo incremental por fratura evitada foram elevadas, todas acima de R$10.000,00 para quaisquer das alternativas de intervenção examinadas, sendo o custo médio estimado das fraturas assistidas dentro da alternativa tradicional inferior a R$ 2.000,00, o que indica que a implementação no SUS de qualquer uma das alternativas em pauta seria questionável segundo critérios de eficiência no uso de recursos e de eqüidade.This article briefly presents the target factors and methods for summarizing evidence employed in a technological evaluation, as well as the underlying logic in their elaboration and utilization in the field of public health. The example is post-menopausal osteoporosis, analyzing the current timeliness of disseminating bone densitometry and technologies to combat osteoporosis in Brazil Available studies on the effects of the respective technologies were reviewed according to the recommended methodology in order to produce a synthesis of the scientific evidence, updated and applied in Brazil. Preliminary cost-effective analyses of different alternatives for intervention (as compared to traditional care) are presented, considering women in and around menopause and at 65 years of age. Despite the optimistic hypotheses, the incremental cost estimates per averted fracture were high, all above R$10,000 for any of the various intervention alternatives, as compared to a mean cost of fractures treated by traditional care estimated at less than R$ 2,000, suggesting that the implementation of any of the target alternatives in the SUS would be questionable according to both efficiency criteria in the use of resources as well as equity

Basic vaginal ph, bacterial vaginosis and aerobic vaginitis: prevalence in early pregnancy and risk of spontaneous preterm delivery, a prospective study in a low socioeconomic and multiethnic South American population

Made available in DSpace on 2014-11-06T17:31:59Z (GMT). No. of bitstreams: 2 Basic vaginal pH, bacterial vaginosis and aerobic.pdf: 263612 bytes, checksum: d3c6238383da12865760f9821785d47f (MD5) license.txt: 1914 bytes, checksum: 7d48279ffeed55da8dfe2f8e81f3b81f (MD5) Previous issue date: 2014Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Unidade de Avaliação de Tecnologias em Saúde. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Faculdade de Medicina. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências Matemáticas e da Natureza. Instituto de Matemática. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Unidade de Avaliação de Tecnologias em Saúde. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Unidade de Pesquisa Clínica. Rio de Janeiro, RJ, Brasil.Centro de Ensino e Pesquisa do Pró-Cardíaco. Pró-Cardíaco. Rio de Janeiro, RJ, Brasil.Background: Bacterial vaginosis (BV) increases the risk of spontaneous preterm deliveries (PD) in developed countries. Its prevalence varies with ethnicity, socioeconomic conditions and gestational age. Aerobic vaginitis (AV) has also been implicated with spontaneous PD. The present study aimed to estimate the prevalence of asymptomatic BV, the accuracy of vaginal pH level to predict BV and to estimate the risk of spontaneous PD = 4.5 were collected to determine the Nugent score; a sample of those smears was also classified according to a modified Donders’ score. Primary outcomes were spontaneous PD 4.5 and = > 5.0 to predict BV status was 100% and 82%, correspondingly; the 5.0 cutoff value doubled the specificity, from 41% to 84%. The incidence of 4.5 was 3.8%. The RR of spontaneous PD =4.5, as compared with those with intermediate state, were 1.24 and 1.86, respectively (Fisher’s exact test, p value = 1; 0.52, respectively, both ns). No spontaneous case of PD or abortion was associated with severe or moderate AV

Randomized controlled trial of probiotics for the prevention of spontaneous preterm delivery associated with intrauterine infection: study protocol

Abstract Background Spontaneous preterm deliveries that occur before the 34th week of gestation, and particularly before the 32nd week of gestation, have been strongly associated to intrauterine infection, ascending from vagina, and represent the largest portion of neonatal deaths and neurological problems. Bacterial vaginosis, characterized by a diminished or absent flora of lactobacilli and increased colonization of several anaerobic or facultative microorganisms, increases two times the risk of preterm delivery before the 34th week. Trials of antibiotics failed to show efficacy and effectiveness against spontaneous preterm birth related to bacterial vaginosis. Some studies indicate benefit from selected probiotics to treat genitourinary infections, including bacterial vaginosis. Objective The purpose of this study is to evaluate the effectiveness of the early administration of selected probiotics to pregnant women with asymptomatic bacterial vaginosis/intermediate degree infection to reduce the occurrence of spontaneous preterm delivery and related neonatal mortality and morbidity. Methods/Design Women attending public prenatal care services in Rio de Janeiro will be screened to select asymptomatic pregnant women, less than 20 weeks' gestation, with no indication of elective preterm delivery. Those with vaginal pH > = 4.5 and a Nugent score between 4 and 10 (intermediate degree infection or bacterial vaginosis) will be randomized to either the placebo or the intervention group, after written informed consent. Intervention consists in the use of probiotics, Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14, 2 capsules a day, each capsule containing more than one million bacilli of each strain, for 6-12 weeks, up to the 24th-25th wk of gestation. Ancillary analyses include quantification of selected cervicovaginal cytokines and genotyping of selected polymorphisms. The randomization process is stratified for history of preterm delivery and blocked. Allocation concealment was designed as well as blinding of women, caregivers and outcome evaluators. The study will be supervised by an independent monitoring committee. Outcomes under study are preterm delivery (< 34- < 32 weeks of gestation) and associated neonatal complications: early neonatal sepsis, bronchopulmonary dysplasia, periventricular leukomalacia, necrotizing enterocolitis, and prematurity-related retinopathy; definitions were adapted from those recommended by the 2002 version of the Vermont-Oxford Network. Trial registration at NIH register: NCT00303082.</p

A randomised controlled trial of probiotics for the prevention of spontaneous preterm delivery associated with bacterial vaginosis: preliminary results

Abstract Background Bacterial vaginosis increases the risk of spontaneous preterm delivery at less than 34 weeks of gestation. Objective The purpose of this study was to evaluate the efficacy of the early administration of selected lactobacilli strains (probiotics) to pregnant women with asymptomatic bacterial vaginosis/intermediate-degree infections to prevent spontaneous premature delivery and associated neonatal morbidity. Methods/Design Asymptomatic pregnant women at less than 20 weeks of gestation, with no indication of elective preterm delivery, with a vaginal pH ≥ 4.5 and Nugent score > 3 were randomly assigned to the placebo or intervention group (oral administration of selected lactobacilli up to the 24th to 26th week of gestation). The randomisation was stratified for the history of premature delivery (HPD) and blocked. The allocation was concealed, and the participating health professionals and patients were blinded. The primary outcome was preterm delivery ( Results In total, 4,204 pregnant women were screened; 320 and 324 individuals were respectively randomly assigned to the placebo and intervention groups, and 62% finished the trial. None of the randomised patients were lost to follow-up. For the non-HPD stratum, the intent-to-treat relative risks of spontaneous premature birth at Conclusions The efficacy of the tested probiotics to prevent preterm delivery among women without a history of preterm delivery was not determined because the study sample was insufficient to estimate statistically significant intent-to-treat effects; additional studies are needed to evaluate this intervention among these women. Trial registration Trial registration at NIH register: NCT00303082. Sources of funding: the Brazilian Health Ministry and the State of Rio de Janeiro Research Foundation.</p

Validity of the risk adjustment approach to compare outcomes Validade da abordagem do ajuste de risco para a comparação de resultados de serviços de saúde

This paper focuses on the issue of the extent to which the present mainstream risk adjustment (RA) methodology for measuring outcomes is a valid and useful tool for quality-improvement activities. The method's predictive and attributional validity are discussed, considering the confounding and effect modification produced by medical care over risk variables' effect. For this purpose, the sufficient-cause model and the counterfactual approach to effect and interaction are tentatively applied to the relationships between risk (prognostic) variables, medical technology, and quality of care. The main conclusions are that quality of care modifies the antagonistic interaction between medical technologies and risk variables, related to different types of responders, as well as the confounding of the effect of risk variables produced by related medical technologies. Thus, confounding of risk factors in the RA method, which limits the latter's predictive validity, is related to the efficacy and complexity of associated medical technologies and to the quality mix of services. Attributional validity depends on the validity of the probabilities estimated for each subgroup of risk (predictive validity) and the percentage of higher-risk patients at each service.<br>Este trabalho focaliza a questão da validade da metodologia usual de ajuste de risco para comparar resultados de serviços de saúde e de sua utilidade para implementar atividades de melhoria da qualidade. As validades preditiva e atributiva do método são discutidas, considerando o confundimento e a modificação de efeito produzidas pela atenção médica sobre o efeito das variáveis de risco. Nesse sentido, as abordagens de causa suficiente e contrafactual para efeito e interação são tentativamente aplicadas às relações entre variáveis de risco, tecnologias médicas e qualidade da assistência. As principais conclusões são de que a qualidade do cuidado modifica a interação antagonista entre tecnologias médicas e variáveis de risco, relacionada a diferentes tipos de respostas, assim como o confundimento do efeito das variáveis de risco produzido pelas tecnologias médicas associadas. Assim, o confundimento dos fatores de risco no método de ajuste de risco, que limita sua validade preditiva, estaria relacionado à eficácia e à complexidade das tecnologias médicas associadas (considerando indicação e performance e sua relação com qualidade) e ao espectro de qualidade dos serviços. A validade atributiva dependeria da validade das probabilidades estimadas para cada subgrupo de risco (validade preditiva) e da porcentagem de pacientes de alto risco de cada serviço