Efficacy and safety assessment of different dosage of benznidazol for the treatment of Chagas disease in chronic phase in adults (MULTIBENZ study): study protocol for a multicenter randomized Phase II non-inferiority clinical trial.

BACKGROUND: Chagas disease (CD) continues to be a neglected infectious disease with one of the largest burdens globally. Despite the modest cure rates in adult chronic patients and its safety profile, benznidazole (BNZ) is still the drug of choice. Its current recommended dose is based on nonrandomized studies, and efficacy and safety of the optimal dose of BNZ have been scarcely analyzed in clinical trials. METHODS/DESIGN: MULTIBENZ is a phase II, randomized, noninferiority, double-blind, multicenter international clinical trial. A total of 240 patients with Trypanosoma CD in the chronic phase will be recruited in four different countries (Argentina, Brazil, Colombia, and Spain). Patients will be randomized to receive BNZ 150 mg/day for 60 days, 400 mg/day for 15 days, or 300 mg/day for 60 days (comparator arm). The primary outcome is the efficacy of three different BNZ therapeutic schemes in terms of dose and duration. Efficacy will be assessed according to the proportion of patients with sustained parasitic load suppression in peripheral blood measured by polymerase chain reaction. The secondary outcomes are related to pharmacokinetics and drug tolerability. The follow-up will be 12 months from randomization to end of study participation. Recruitment was started in April 2018. CONCLUSION: This is a clinical trial conducted for the assessment of different dose schemes of BNZ compared with the standard treatment regimen for the treatment of CD in the chronic phase. MULTIBENZ may help to clarify which is the most adequate BNZ regimen in terms of efficacy and safety, predicated on sustained parasitic load suppression in peripheral blood. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03191162. Registered on 19 June 2017.

Clinical and economic impact of urinary tract infections caused by ESBL-producing Escherichia coli requiring hospitalization: A matched cohort study.

OBJECTIVE: To analyze the clinical and economic impact of urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli requiring hospitalization. METHODS: Matched cohort study including adults with UTI caused by ESBL-producing E. coli admitted to a tertiary care hospital in Barcelona, Spain, between August 2010 and July 2013. Demographic, clinical and economic data were analyzed. RESULTS: One hundred and twenty episodes of UTI were studied: 60 due to ESBL-producing E. coli and 60 due to non-ESBL-producing E. coli. Bivariate analysis showed that prior antimicrobial treatment (p = 0.007) and ESBL production (p < 0.001) were related to clinical failure during the first 7 days. Multivariate analysis selected ESBL as the sole risk factor for clinical failure (p = 0.002). Regarding the economic impact of infections caused by ESBL-producing E. coli, an ESBL-producing infection cost more than a non-ESBL-producing E. coli infection (mean €4980 vs. €2612). Looking at hospital expenses separately, the total pharmacy costs and antibiotic costs of ESBL infections were considerably higher than for non-ESBL infections (p < 0.001), as was the need for outpatient parenteral antibiotic therapy (OPAT) and its related costs. Multivariate analysis performed for the higher costs of UTI episodes found statistically significant differences for males (p = 0.004), chronic renal failure (p = 0.025), ESBL production (p = 0.008) and OPAT (p = 0.009). CONCLUSION: UTIs caused by EBSL-producing E. coli requiring hospital admission are associated with worse clinical and economic outcomes.

A rapid questionnaire assessment of environmental exposures to pregnant women in the INTERGROWTH-21st Project.

Impaired fetal growth and preterm birth are the leading causes of neonatal and infant mortality worldwide and there is a growing scientific literature suggesting that environmental exposures during pregnancy may play a causal role in these outcomes. Our purpose was to assess the environmental exposure of the Fetal Growth Longitudinal Study (FGLS) participants in the multinational INTERGROWTH-21(st) Project. First, we developed a tool that could be used internationally to screen pregnant women for such exposures and administered it in eight countries on a subsample (n = 987) of the FGLS participants. The FGLS is a study of fetal growth among healthy pregnant women living in relatively affluent areas, at low risk of adverse pregnancy outcomes and environmental exposures. We confirmed that most women were not exposed to major environmental hazards that could affect pregnancy outcomes according to the protocol's entry criteria. However, the instrument was able to identify some women that reported various environmental concerns in their homes such as peeling paint, high residential density (>1 person per room), presence of rodents or cockroaches (hence the use of pesticides), noise pollution and safety concerns. This screening tool was therefore useful for the purposes of the project and can be used to ascertain environmental exposures in studies in which the primary aim is not focused on environmental exposures. The instrument can be used to identify subpopulations for more in-depth assessment, (e.g. environmental and biological laboratory markers) to pinpoint areas requiring education, intervention or policy change.

Translating research into practice: the introduction of the INTERGROWTH-21st package of clinical standards, tools and guidelines into policies, programmes and services.

The INTERGROWTH-21(st) Project has generated a package of international clinical standards, tools and guidelines. It is now necessary to plan for the next phase of the project: the translation of the research findings into practice through its global dissemination. The plan is to pre-empt barriers to implementation by drawing from the published literature; gathering views and perspectives from policy makers, programmers and practitioners; incorporating input from local 'champions', and collecting and analysing data generated by a monitoring and evaluation system. Working at the global, regional, national and local levels will enable wide dissemination of the package, as well as increase the scope for adaptation and integration in diverse clinical contexts. We seek maximum uptake of the package in policies, guidelines and clinical practice to improve the quality of care offered to mothers and newborns. The strategy will also enhance our understanding of the effectiveness of different approaches to the translation of evidence into practice.

[Amenable mortality as indicator of effectiveness of health care services in Spain before and after transferences]. / Mortalidad reducible como indicador de efectividad de los servicios sanitarios en España antes y después de las transferencias.

OBJECTIVE: To describe the evolution of amenable mortality (MRASS) in Spain and to evaluate differences in trend patterns before and after health care services were transferred to local authorities. METHODS: MRASS was defined from a list of causes of death used in other studies. We analyzed the change in sex-age-standardized death rates of MRASS in two periods: 1999-2001 and 2006-2008, just before, and five years after, the health care transfers were completed. RESULTS: MRASS represented 24% of deaths in persons from 0 to 74 years old. MRASS has seen a reduction (19.4%) between the two periods over and above other causes of mortality (14.5%). The group of causes of mortality which showed most reduction: ischemic heart disease (28%), other vascular disease (27%), surgical conditions and surgical-medical errors (26%), and diabetes (22.5%). Although there were differences between the districts, health care transfers have not created significant variations in MRASS. Navarra and Madrid showed lower rates of MRASS, and the Canary Islands, Asturias, Andalusia, Ceuta and Melilla had higher rates. The Balearic Islands showed the greatest reduction in MRASS. CONCLUSIONS: MRASS constitutes an important proportion of trends of mortality in persons between 0-74 years. It has declined in all districts. Even though there were large differences between districts, there does not appear to be any direct influence due to health care transfer in amenable mortality trends. In spite of limitations, MRASS is an indicator to be considered when monitoring and detecting weaknesses in the effectiveness of health care systems.

[Assessment of prescription in discharge reports at a university hospital]. / Evaluación de la prescripción de medicamentos en los informes de alta en un hospital universitario.

OBJECTIVE: To determine and analyze drug prescription at hospital discharge, mainly regarding generic drug use, use of novel but irrelevant therapeutic agents and use of low therapeutic value drugs (LTVD). MATERIAL AND METHODS: In a retrospective study 195 discharge reports from 11 different departments in a 450-bed general hospital were analyzed for a monthly period. An Access database allowed us to record the number of prescriptions, each drugs therapeutic group according to the Anatomical Therapeutic Chemical (ATC) Classification System, prescribed drugs for which generics are available, prescribed C-group drugs, LTVD drugs, etc. RESULTS: Following an analysis of results, only 6.17% of all drugs were prescribed according to their generic name, when this would have been possible in 22.8%. If only the most efficient agents had been prescribed, savings would have amounted to 589.3 Euros. In all, 1.28% of prescribed drugs were LTVD, and 1.15% had irrelevant therapeutic value. CONCLUSION: Although specialized medical prescription represents a minimum of total prescriptions in a healthcare area, measures intended to improve quality will have a positive impact on primary care prescriptions. These measures include information to physicians on more efficient preparations, plus the design of a Pharmacotherapeutic Guide to unify pharmacologic criteria in the Area.

The epidemiology of syphilis in pregnancy.

This study evaluated the magnitude, risk factors and outcomes of syphilis in pregnancy in a large cohort of women in four countries participating in the World Health Organization (WHO) antenatal care trial. All women attending the first prenatal care at each selected clinic were enrolled. Screening at the first antenatal visit was routinely performed with either rapid plasma reagin or Venereal Disease Research Laboratory and confirmed by fluorescent treponemal antibody absorption. All women also had the same syphilis tests after delivery. The initial prevalence, the incidence during pregnancy and the overall prevalence of syphilis at delivery were 0.9%, 0.4% and 1.3% respectively. Risk factors for syphilis during pregnancy were younger age for the incidence and older age and a history of stillbirth for the prevalence. Women with syphilis during pregnancy had significantly more adverse outcomes. We support the recommendation that in addition to the initial testing, a second routine test for syphilis ought to be established early in the third trimester even in low prevalence areas.

Maternal height and newborn size relative to risk of intrapartum caesarean delivery and perinatal distress.

OBJECTIVE: To estimate the changes, in risk of intrapartum caesalrean delivery and perinatal distress that may be introduced through increased birth size, resulting from interventions such as improving nutrition of the mother; and to characterise delivery risk relative to maternal stature by birth size. DESIGN: Model these risks using data from the Guatemalan Perinatal Study. SETTING: The antenatal clinic of the Gynaecology and Obstetrics Hospital of the Guatemalan Social Security Institute in Guatemala City serving predominantly working class women. POPULATION: Women who had their first prenatal visit between April 1984 and January 1986. METHODS: Multivariate logistic regression models were developed to estimate incidence of intrapartum caesarean delivery and perinatal distress and used to calculate changes in risk associated with changes in size. MAIN OUTCOME MEASURES: Incidences of intrapartum caesarean delivery and perinatal distress. RESULTS: A woman of 146cm height (-1 SD) relative to another of 160 cm (+1 SD) has a 2.5 times higher risk of intrapartum caesarean delivery. An increase in newborn head circumference and weight (from -1 SD to +1 SD) are each independently associated with an increase in risk of intrapartum caesarean delivery (2.0 times and 1.5 times. respectively). An increase in birthweight from 2,450 g to 2,550 g is associated with a decrease in risk of perinatal distress of 34/1,000 cases and an increase in risk of intrapartum caesarean delivery of 8/1,000 cases. CONCLUSIONS: Increases in fetal growth comparable to those attributable to improved nutrition during pregnancy are associated with a larger decrease in risk of perinatal distress relative to the increase in risk of intrapartum caesarean delivery for the mother. Greater maternal stature is associated with lower risk of intrapartum caesarean delivery.

[Clinical usefulness and cost-effectiveness of transbronchial needle aspiration for the diagnosis of mediastinal adenopathy]. / Utilidad clínica y coste-efectividad de la punción-aspiración transbronquial en el diagnóstico de adenopatías mediastínicas.

Transbronchial needle aspiration (TBNA) of mediastinal or hilar enlarged lymph nodes is a useful and safe technique. Nevertheless, its use has not become widespread, and the necessity of a specific training to obtain good results has been reported. In order to evaluate the clinical usefulness and cost-effectiveness of TBNA in inexperienced brochoscopists in this technique, a prospective study was conducted of this technique used in all patients with a chest CT with paratracheobronchial lymph nodes larger than 10 mm who had a fiberbronchoscopy ordered. TBNA was performed in 66 lymph node staging in 59 patients. In 76% of cases adequate specimens were obtaned, and a cytohistologic diagnosis was established in 59%. In 44% of patients, TBNA avoided other more invasive diagnostic procedures. Had TBNA not been performed, cost was estimated to have been at least five times higher. We conclude that TBNA could be a useful cost-effective technique in inexperienced teams.

WHO antenatal care randomised trial for the evaluation of a new model of routine antenatal care.

BACKGROUND: We undertook a multicentre randomised controlled trial that compared the standard model of antenatal care with a new model that emphasises actions known to be effective in improving maternal or neonatal outcomes and has fewer clinic visits. METHODS: Clinics in Argentina, Cuba, Saudi Arabia, and Thailand were randomly allocated to provide either the new model (27 clinics) or the standard model currently in use (26 clinics). All women presenting for antenatal care at these clinics over an average of 18 months were enrolled. Women enrolled in clinics offering the new model were classified on the basis of history of obstetric and clinical conditions. Those who did not require further specific assessment or treatment were offered the basic component of the new model, and those deemed at higher risk received the usual care for their conditions; however, all were included in the new-model group for the analyses, which were by intention to treat. The primary outcomes were low birthweight (<2500 g), pre-eclampsia/eclampsia, severe postpartum anaemia (<90 g/L haemoglobin), and treated urinary-tract infection. There was an assessment of quality of care and an economic evaluation. FINDINGS: Women attending clinics assigned the new model (n=12568) had a median of five visits compared with eight within the standard model (n=11958). More women in the new model than in the standard model were referred to higher levels of care (13.4% vs 7.3%), but rates of hospital admission, diagnosis, and length of stay were similar. The groups had similar rates of low birthweight (new model 7.68% vs standard model 7.14%; stratified rate difference 0.96 [95% CI -0.01 to 1.92]), postpartum anaemia (7.59% vs 8.67%; 0.32), and urinary-tract infection (5.95% vs 7.41%; -0.42 [-1.65 to 0.80]). For pre-eclampsia/eclampsia the rate was slightly higher in the new model (1.69% vs 1.38%; 0.21 [-0.25 to 0.67]). Adjustment by several confounding variables did not modify this pattern. There were negligible differences between groups for several secondary outcomes. Women and providers in both groups were, in general, satisfied with the care received, although some women assigned the new model expressed concern about the timing of visits. There was no cost increase, and in some settings the new model decreased cost. INTERPRETATIONS: Provision of routine antenatal care by the new model seems not to affect maternal and perinatal outcomes. It could be implemented without major resistance from women and providers and may reduce cost.

How effective is antenatal care in preventing maternal mortality and serious morbidity? An overview of the evidence.

This is an overview of evidence of the effectiveness of antenatal care in relation to maternal mortality and serious morbidity, focused in particular on developing countries. It concentrates on the major causes of maternal mortality, and traces their antecedent morbidities and risk factors in pregnancy. It also includes interventions aimed at preventing, detecting or treating any stage along this pathway during pregnancy. This is an updated and expanded version of a review first published by the World Health Organization (WHO) in 1992. The scientific evidence from randomised controlled trials and other types of intervention or observational study on the effectiveness of these interventions is reviewed critically. The sources and quality of available data, and possible biases in their collection or interpretation are considered. As in other areas of maternal health, good-quality evidence is scarce and, just as in many aspects of health care generally, there are interventions in current practice that have not been subjected to rigorous evaluation. A table of antenatal interventions of proven effectiveness in conditions that can lead to maternal mortality or serious morbidity is presented. Interventions for which there is some promising evidence, short of proof, of effectiveness are explored, and the outstanding questions formulated. These are presented in a series of tables with suggestions about the types of study needed to answer them.

Randomized clinical trials in perinatology in Latin America.

Latin America needs means to obtain accurate figures about its health conditions in order to apply its resources to priority areas. In addition, health actions must be carefully evaluated to assess their impact, operation and costs. The randomized clinical trial (RCT) is the only design able to show the effectiveness of interventions of moderate effect. Also, it gives appropriate information about the expected effect of the interventions and implies an expediate implementation of interventions in the same places where the project has been performed. In a review of RCTs performed in Latin America on perinatal medicine it can be concluded that some of the focus of research is irrelevant to the region and there is not an orientation towards the cooperative solution of predominant problems in the area. It is imperative for researchers, in Latin America to initiate joint activities in order to assess which are the research priorities of the area, to focus their research on these priorities and to join their efforts in collaborative studies.

La Paz Hemophilia Center, 1967-1992: people, events, and memories.

In 1967, once urgent blood requirements had been resolved in La Paz Hospital, Madrid, Spain, and adequate supplies of plasma for cryoprecipitation, therefore, being available, a Hemophilia Unit (later Hemophilia Center) was set up to attend to the comprehensive care of hemophilia patients and patients with other coagulopathies. This Center covers a regional area and also a national area for referrals and normally attends 600 patients. In this Center the Spanish Social Security Hemophilia Association was created. In 1983 the first cases of AIDS appeared, occasioning the change from standard factor VIII concentrates to the heat-treated concentrates that had recently appeared on the market. At present the Center is responsible for the medical attention of those hemophilia patients affected by HIV.

The effect of maternal work on fetal growth and duration of pregnancy: a prospective study.

The effect on birth outcome of work requiring different degrees of physical exertion was examined among 15,786 pregnant women who were followed through the Guatemalan Social Security Institute's hospital. Work inside and outside the home was ascertained through a questionnaire administered to each women before delivery. Odds ratios were adjusted for household income, maternal height and age, and birthweight of previous infant. Women with three or more children and no household help were at increased risk for small-for-gestational-age (SGA) births compared with women with family (odds ratio (OR) 1.79; 95% confidence interval (CI) 1.31, 2.47) or hired help (OR 2.0; 95% CI 1.16 to 3.33). Compared with office work, manual work increased the risk for an SGA (OR 1.32; 95% CI 1.12 to 1.56) and SGA/preterm birth (OR 2.56; 95% CI 1.10 to 5.96). Work in a standing compared with sitting position significantly increased the risk for a preterm birth (OR 1.56; 95% CI 1.04 to 2.60). There was a significant positive trend in frequency of SGA and SGA/preterm birth with an increase in the physical demands at work, as measured by an activity score. These data suggest that interventions to reduce physical exertion among pregnant women could improve birth outcome.

[Identification of pregnant patients at risk of delivering low birthweight infants in urban areas of Guatemala]. / Identificacion de embarazos con riesgo de producir ninos de bajo peso al nacer en areas urbanas de Guatemala.

PIP: A prospective epidemiologic study of pregnant women obtaining prenatal care at a social security hospital in Guatemala City was the basis for an attempt to develop a method of identifying early in pregnancy women at risk of having low birth weight infants. Existing classifications of risk are not completely satisfactory for low income women in urban areas of developing countries. The sample included 17,135 women seen between April 1984 and January 1986. Women who had no prenatal care or who obtained it elsewhere were excluded. Social workers interviewed each woman at the 1st prenatal visit to obtain sociodemographic data. The nurses or physicians attending the women completed forms based on perinatal records developed by the Latin American Center for Perinatology and Human Development and adapted to local needs. A final visit was made just after delivery to complete the information in each file. Great care was taken to assure that the 24 examiners used the same standards for all measurement variables. The standardized data collection techniques were evaluated in a study of agreement between observers. The study was conducted in 4 sections covering sociodemographic variables, obstetric history, prenatal variables, and labor and delivery. Taking into account the size of the sample and the number of observers, it was concluded that the data were of acceptable quality. It is strongly recommended that periodic evaluation of the quality of data collected be included in all perinatal epidemiologic studies. It was also concluded that longitudinal studies of perinatal risk factors might not be needed in all regions or health areas; the association between the best known risk factors and the evolution of pregnancy has been established, and with few exceptions it appears to be relatively constant in all populations. It is recommended that perinatal services reduce the amount of data routinely collected to a minimum and apply the quality control and standardization procedures to a sample of patients and to all personnel completing records. This would assure an acceptable quality of data as a basis for medical or public health decision making. Relevant additional variables could be added as needed^ieng