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.

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 <34 and <37 weeks' gestation of BV and AV. METHODS: Women attending prenatal public services in Rio de Janeiro were screened to select asymptomatic pregnant women, < 20 weeks' gestation, with no indication for elective PD and without risk factors of spontaneous PD. Vaginal smears of women with vaginal pH > = 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 < 34 and <37 weeks' gestation and abortion. RESULTS: Prevalence of asymptomatic BV was estimated in 28.1% (n = 1699); 42.4% of the smears were collected before 14 weeks' gestation. After an 8-week follow up, nearly 40% of the initially BV positive women became BV negative. The prevalence of BV among white and black women was 28.1% (95% CI: 24.6%-32.0%) and 32.5% (95% CI: 28.2%-37.2%), respectively. The sensitivity of vaginal pH= > 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 < 37 weeks' spontaneous PDs among BV pregnant women with a pH= > 4.5 was 3.8%. The RR of spontaneous PD < 34 and <37 weeks among BV women with pH > =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. CONCLUSIONS: A high prevalence of asymptomatic BV was observed without statistically significant difference between black and white women. The RRs of spontaneous PD < 34 and <37 weeks among women with BV, as compared with those with intermediate state were not statistically significant but were consistent with those found in the literature.

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. TRIAL REGISTRATION: Trial registration at NIH register: NCT00303082. Sources of funding: the Brazilian Health Ministry and the State of Rio de Janeiro Research Foundation.

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.

[Meta-analysis of clinical trials on family intervention in schizophrenia]. / Meta-análise de ensaios clínicos de intervenção familiar na condição esquizofrenia.

The present study aimed to assess the efficacy of cognitive-behavioral family interventions by relatives of schizophrenic patients under community care, specifically targeting relapse and family burden as outcomes. Independent researchers conducted the analyses of the pertinence and quality of trials identified through a search strategy, following a previously developed protocol. Eleven randomized or quasi-randomized trials were selected. The summary relative risk of relapse using the fixed effects model was favorable to family intervention, with estimated efficacy reaching nearly 60% (50%-70%). Summary relative risk in the cognitive-behavioral therapy trials subgroup [RR = 0.43 (0.28-0.67)] was equivalent to that of the behavioral therapy subgroup [RR = 0.37 (0.23-0.60)] and the "pragmatic" subgroup [RR = 0.37 (0.21-0.66)], although the "pragmatic" trials were generally analyzed for effective treatment. The difference in summary overall risk of relapse was nearly 30% using the random effects model. Only four trials analyzed family burden as outcome, including different dimensions of burden. Results of individual trials were generally favorable to family intervention, for both the objective and subjective dimensions.

Meta-análise de ensaios clínicos de intervenção familiar na condição esquizofrenia: [revisão] / Meta-analysis of clinical trials on family intervention in schizophrenia

O objetivo da presente revisão sistemática foi avaliar a eficácia da intervenção familiar de base cognitivo-comportamental para portadores de esquizofrenia em tratamento ambulatorial, com relação aos desfechos recaída e sobrecarga familiar. Pesquisadores independentes conduziram as análises da pertinência e da qualidade dos ensaios identificados pela estratégia de busca utilizada, seguindo protocolo previamente elaborado. Foram selecionados 11 ensaios randomizados ou quasi-randomizados. Para o desfecho recaída, o risco relativo sumário, pelo modelo de efeitos fixos, foi favorável à intervenção familiar para o conjunto dos ensaios, com eficácia de cerca de 60 por cento (50 por cento-70 por cento). O risco relativo sumário dos ensaios do subgrupo cognitivo-comportamental [RR = 0,43 (0,28-0,67)] foi equivalente ao do subgrupo comportamental [RR = 0,37 (0,23-0,60)] e ao do subgrupo pragmático [RR = 0,37 (0,21-0,66)], embora a forma de análise dos ensaios pragmáticos tenha sido, em geral, por tratamento efetivo. A diferença de riscos sumária geral foi estimada em cerca de 30 por cento pelo modelo de efeitos randômicos. Apenas quatro ensaios analisaram o desfecho sobrecarga familiar, abrangendo, diferentemente, algumas das dimensões objetivas e subjetivas. Os resultados dos estudos individuais foram, em geral, favoráveis à intervenção familiar.

The present study aimed to assess the efficacy of cognitive-behavioral family interventions by relatives of schizophrenic patients under community care, specifically targeting relapse and family burden as outcomes. Independent researchers conducted the analyses of the pertinence and quality of trials identified through a search strategy, following a previously developed protocol. Eleven randomized or quasi-randomized trials were selected. The summary relative risk of relapse using the fixed effects model was favorable to family intervention, with estimated efficacy reaching nearly 60 percent (50 percent-70 percent). Summary relative risk in the cognitive-behavioral therapy trials subgroup [RR = 0.43 (0.28-0.67)] was equivalent to that of the behavioral therapy subgroup [RR = 0.37 (0.23-0.60)] and the pragmatic subgroup [RR = 0.37 (0.21-0.66)], although the pragmatic trials were generally analyzed for effective treatment. The difference in summary overall risk of relapse was nearly 30 percent using the random effects model. Only four trials analyzed family burden as outcome, including different dimensions of burden. Results of individual trials were generally favorable to family intervention, for both the objective and subjective dimensions.

Revisões sistemáticas de antibioticoprofilaxia em cesarianas / Systematic reviews of antibiotic prophylaxis in cesareans

O objetivo do trabalho foi analisar a evidência científica disponível sobre os efeitos da antibioticoprofilaxia em cesarianas. As presentes revisões sistemáticas compreenderam um exame detalhado da qualidade do desenho e da execução assim como da heterogeneidade clínica entre os ensaios. A meta-análise dos ensaios placebo-controlados (27 estudos) apontou eficácia aproximada de 65 por cento para ambos os desfechos estudados, endometrite e infecção da ferida cirúrgica (IFC), correspondendo a uma queda da incidência de 11 por cento e 5 por cento, respectivamente. As análises de sensibilidade mostraram efeitos sumários semelhantes aos observados para o conjunto dos ensaios. O subgrupo dos 12 ensaios de cesáreas não eletivas indicou benefício importante da antibioticoprofilaxia para ambos os desfechos, correspondente a uma queda de 14 por cento (endometrite) e 5 por cento (IFC). Para cesáreas eletivas (dois ensaios), não foi mostrado benefício relevante. A evidência obtida dos ensaios comparativos de doses foi limitada devido a falhas metodológicas importantes e ao pequeno número de pacientes envolvidas (três ensaios). Os ensaios comparativos de antimicrobianos (sete estudos) não evidenciaram diferença de eficácia entre os dois esquemas analisados, cefalosporinas de 1ª e de 2ª geração.

This study reviews the available evidence on the efficacy of antibiotic prophylaxis in cesarean sections. The study included a detailed analysis of the quality of design and performance and the clinical heterogeneity of selected clinical trials. Meta-analysis of placebo-controlled trials estimated an efficacy of some 65 percent for the two study endpoints, endometritis and surgical wound infection, corresponding to a decrease in infection rates of some 11 percent and 5 percent, respectively. Sensitivity analyses showed summary effects similar to those observed for all studies. Results for the non-elective cesarean sections subgroup (12 studies) indicated a relevant benefit for both endpoints, corresponding to a decrease in incidence rates of some 14 percent (endometritis) and 5 percent (surgical infection wound). For elective surgeries (two trials), no relevant benefit was found. Evidence from comparative trials on number of doses was limited due to important methodological shortcomings and to the small number of patients enrolled (three trials). Comparative drug trials (seven studies) did not show evidence of different performance between first and second-generation cephalosporins.

[Systematic reviews of antibiotic prophylaxis in cesareans]. / Revisões sistemáticas de antibioticoprofilaxia em cesarianas.

This study reviews the available evidence on the efficacy of antibiotic prophylaxis in cesarean sections. The study included a detailed analysis of the quality of design and performance and the clinical heterogeneity of selected clinical trials. Meta-analysis of placebo-controlled trials estimated an efficacy of some 65% for the two study endpoints, endometritis and surgical wound infection, corresponding to a decrease in infection rates of some 11% and 5%, respectively. Sensitivity analyses showed summary effects similar to those observed for all studies. Results for the non-elective cesarean sections subgroup (12 studies) indicated a relevant benefit for both endpoints, corresponding to a decrease in incidence rates of some 14% (endometritis) and 5% (surgical infection wound). For elective surgeries (two trials), no relevant benefit was found. Evidence from comparative trials on number of doses was limited due to important methodological shortcomings and to the small number of patients enrolled (three trials). Comparative drug trials (seven studies) did not show evidence of different performance between first and second-generation cephalosporins.

[Systematic review and meta-analysis of antibiotic prophylaxis in abdominal hysterectomy]. / Revisão sistemática e meta-análise da antibioticoprofilaxia na histerectomia abdominal.

The objective of the present study was to assess the available evidence regarding antibiotic prophylaxis taking the case of abdominal hysterectomy, as an aid to decisions related to coverage and to the development of evidence-based clinical guidelines. Using a previously elaborated protocol, the pertinence and quality of double-blind, randomized, placebo-controlled trials were examined. Clinical heterogeneity among studies was also analyzed. The studies were found to be homogeneous, considering p > 0.10 as the significance level for rejecting heterogeneity. Combination of the 16 selected studies resulted in a summary rate ratio of 0.49 (95%CI: 0.41-0.59), i.e., efficacy of 51%, and in a summary rate difference of 11% (95%CI: 8-14), utilizing the fixed effects model. Results according to the random effects model were very similar. Exploratory analysis of subgroups of single versus multiple doses did not indicate more benefit for multiple dose interventions. Evidence from comparative trials is insufficient to consider third-generation cephalosporins more efficacious than first-generation ones.

[Technology assessment in health care: methodological and operational questions]. / Avaliação tecnológica em saúde: questões metodológicas e operacionais.

Coverage policies, elaboration of clinical guidelines, and health services evaluation and management are increasingly dependent on formal technology assessments in developed countries. The objective of this study was to identify methodological and operational barriers, as well as strategies to enhance technology assessment activities, with a focus on Brazil. Methodological limitations to the elaboration of systematic reviews and economic evaluations were reviewed, including equity considerations, as well as attempts to overcome those problems; regulatory efforts in developed countries are acknowledged as a lever for methodological advances in the field. Operational barriers to the elaboration and utilization of technology assessment reports in Brazil are related to the adequacy and availability of relevant data as well as to the scarcity of trained researchers and decision-makers. Besides political barriers, constraints to the implementation of technology assessment recommendations are generally posed by methodological and transferability limitations, by communication deficits, and by factors related to the decision-making context external to the assessment itself, like availability of resources, budget flexibility, and transactional costs.

Revisão sistemática e meta-análise da antibioticoprofilaxia na histerectomia abdominal / Systematic review and meta-analysis of antibiotic prophylaxis in abdominal hysterectomy

O presente estudo objetivou examinar a evidência científica disponível relativa à eficácia da antibioticoprofilaxia no caso da histerectomia, no sentido de subsidiar decisões relativas a financiamento e contribuir para a produção de diretrizes clínicas baseadas em evidências. Usando protocolo previamente elaborado, os ensaios disponíveis foram analisados quanto à pertinência e qualidade. A heterogeneidade clínica dos ensaios selecionados também foi examinada. O teste de heterogeneidade estatística sugeriu que os estudos são homogêneos, considerando-se o valor de p > 0,10 como nível de significância para rejeitar a heterogeneidade. A combinação dos resultados dos 16 ensaios placebo-controlados selecionados resultou em razão de taxas sumárias de 0,49 (IC95 por cento: 0,41-0,59), ou seja, em eficácia de 51 por cento, e em diferença de taxas sumárias de 11 por cento (IC95 por cento: 8-14 por cento), utilizando-se o modelo de efeitos fixos. Os resultados observados usando-se o modelo de efeitos aleatórios foram muito semelhantes. A análise exploratória de esquemas de dose única versus doses múltiplas não indicou maior eficácia para esquemas de doses múltiplas. A evidência disponível, baseando-se em ensaios comparativos, é insuficiente para inferir que existe vantagem em usar cefalosporinas de terceira geração frente àquelas de primeira.

Avaliação tecnológica em saúde: questões metodológicas e operacionais / Technology assessment in health care: methodological and operational questions

A cobertura de tecnologias/procedimentos, assim como os processos de elaboração de diretrizes clínicas, planejamento, gerência e avaliação de serviços e programas por parte dos governos dos países desenvolvidos cada vez mais dependem de avaliações tecnológicas formais. O objetivo deste trabalho foi apontar dificuldades de caráter metodológico e operacional e caminhos relevantes ao sucesso de atividades de avaliação tecnológica, particularmente, no Brasil. Foram revisadas as limitações atuais para a elaboração de revisões sistemáticas e avaliações econômicas, incluindo a questão da eqüidade e as tentativas de avanços nesse campo, propiciadas por critérios de difusão em países desenvolvidos. As dificuldades operacionais para a elaboração e utilização de avaliações tecnológicas dependem, em nosso país, da adequação e disponibilização de dados e da formação de pesquisadores e tomadores de decisão nesse campo. Além das barreiras políticas, a implementação de resultados das avaliações tecnológicas é dificultada, principalmente, por limitações metodológicas e validade de transferência de seus resultados para diferentes contextos, falhas de comunicação de várias naturezas e fatores do contexto da tomada de decisão externos à avaliação tecnológica, como disponibilidade de recursos, flexibilidade orçamentária e custos transacionais.