Claudio Vera

Potential impact on estimated treatment effects of information lost to follow-up in randomised controlled trials (LOST-IT): systematic review

Objective To assess the reporting, extent, and handling of loss to follow-up and its potential impact on the estimates of the effect of treatment in randomised controlled trials. Design Systematic review. We calculated the percentage of trials for which the relative risk would no longer be significant under a number of assumptions about the outcomes of participants lost to follow-up. Data sources Medline search of five top general medical journals, 2005-07. Eligibility criteria Randomised controlled trials that reported a significant binary primary patient important outcome. Results Of the 235 eligible reports identified, 31 (13%) did not report whether or not loss to follow-up occurred. In reports that did give the relevant information, the median percentage of participants lost to follow-up was 6% (interquartile range 2-14%). The method by which loss to follow-up was handled was unclear in 37 studies (19%); the most commonly used method was survival analysis (66, 35%). When we varied assumptions about loss to follow-up, results of 19% of trials were no longer significant if we assumed no participants lost to follow-up had the event of interest, 17% if we assumed that all participants lost to follow-up had the event, and 58% if we assumed a worst case scenario (all participants lost to follow-up in the treatment group and none of those in the control group had the event). Under more plausible assumptions, in which the incidence of events in those lost to follow-up relative to those followed-up is higher in the intervention than control group, results of 0% to 33% trials were no longer significant. Conclusion Plausible assumptions regarding outcomes of patients lost to follow-up could change the interpretation of results of randomised controlled trials published in top medical journals.

LOST to follow-up Information in Trials (LOST-IT): a protocol on the potential impact

BackgroundIncomplete ascertainment of outcomes in randomized controlled trials (RCTs) is likely to bias final study results if reasons for unavailability of patient data are associated with the outcome of interest. The primary objective of this study is to assess the potential impact of loss to follow-up on the estimates of treatment effect. The secondary objectives are to describe, for published RCTs, (1) the reporting of loss to follow-up information, (2) the analytic methods used for handling loss to follow-up information, and (3) the extent of reported loss to follow-up.MethodsWe will conduct a systematic review of reports of RCTs recently published in five top general medical journals. Eligible RCTs will demonstrate statistically significant effect estimates with respect to primary outcomes that are patient-important and expressed as binary data. Teams of 2 reviewers will independently determine eligibility and extract relevant information from each eligible trial using standardized, pre-piloted forms. To assess the potential impact of loss to follow-up on the estimates of treatment effect we will, for varying assumptions about the outcomes of participants lost to follow-up (LTFU), calculate (1) the percentage of RCTs that lose statistical significance and (2) the mean change in effect estimate across RCTs. The different assumptions we will test are the following: (1) none of the LTFU participants had the event; (2) all LTFU participants had the event; (3) all LTFU participants in the treatment group had the event; none of those in the control group had it (worst case scenario); (4) the event incidence among LTFU participants (relative to observed participants) increased, with a higher relative increase in the intervention group; and (5) the event incidence among LTFU participants (relative to observed participants) increased in the intervention group and decreased in the control group.DiscussionWe aim to make our objectives and methods transparent. The results of this study may have important implications for both clinical trialists and users of the medical literature.

Prevalence and predictors of exclusive breastfeeding at hospital discharge.

OBJECTIVE: To estimate the population-based prevalence and predictors of exclusive breastfeeding at hospital discharge in singleton and twin term newborns. METHODS: We studied all hospital births in the province of Ontario, Canada, between April 1, 2009, and March 31, 2010, to perform a retrospective cohort study. We included live singleton and twin births, at term (37 0/7 weeks of gestation to 41 6/7 weeks of gestation), with information about feeding at maternal–newborn discharge. Descriptive statistics were performed and logistic regression was used to identify factors related to exclusive breastfeeding. RESULTS: Our study population consisted of 92,364 newborns, of whom 56,865 (61.6%) were exclusively breastfed at discharge. Older, nonsmoking, higher-income mothers with no pregnancy complications or reproductive assistance were more likely to breastfeed. Mothers of twins were less likely to exclusively breastfeed (adjusted odds ratio [OR] 0.30, 95% confidence interval [CI] 0.25–0.36) as were women who did not attend prenatal classes (adjusted OR 0.80, 95% CI 0.76–0.83). Compared with patients of obstetricians (57%), women cared for by midwives (87%, adjusted OR 4.49, 95% CI 4.16–4.85) and family physicians (67%, adjusted OR 1.54, 95% CI 1.47–1.61) were more likely to exclusively breastfeed. Breastfeeding after a planned (50%, adjusted OR 0.56, 95% CI 0.52–0.60) or unplanned (48%, adjusted OR 0.48, 95% CI 0.44–0.51) cesarean delivery was less common than after a spontaneous vaginal birth (68%). Neonates born at 39, 38, and 37 weeks of gestation (compared with 41 weeks of gestation) were increasingly less likely to breastfeed (adjusted ORs 0.93, 95% CI 0.89–0.98; 0.84, 95% CI 0.80–0.88; and 0.71, 95% CI 0.67–0.76). CONCLUSION: This large population-based study found that fewer than two thirds of term newborns are exclusively breastfed at hospital discharge, substantially lower than previously reported. LEVEL OF EVIDENCE: II

Maternal hypertriglyceridemia: A link between maternal overweight-obesity and macrosomia in gestational diabetes

Infants born from overweight and obese mothers with glucose‐controlled gestational diabetes (GDM) tend to be large‐for‐gestational age (LGA). It is hypothesized that this is due to an excessive rise in maternal triglyceride levels.

Women's intentions to breastfeed: a population‐based cohort study

Given that intention to breastfeed is a strong predictor of breastfeeding initiation and duration, the objectives of this study were to estimate the population‐based prevalence and the factors associated with the intention to breastfeed.

La edad de la mujer como factor de riesgo de mortalidad materna, fetal, neonatal e infantil

Background: Adolescent pregnancy and advanced maternal age are associated with increased risk for maternal, perinatal and infant death. However, the maternal age with the lowest reproductive risk has not been established. Aim: To determine the range of maternal age with the lowest reproductive risk. Material and methods: A population-based study (2005-2010) was performed analyzing raw data from vital statistics yearbooks of the National Institute of Statistics of Chile. The association of maternal, fetal, neonatal and infant mortality with maternal age was analyzed. The latter was stratified in quinquenniums, between ages 10 and 54 years. Maternal, fetal, neonatal and infant mortality rates were calculated for each quinquennium. The lowest rate was selected as a control group for risk analysis, which was estimated according to Odds Ratio with 95% confidence intervals. Results: Women of 20-29, 25-34 and under 30 years, had the lowest rate of fetal, neonatal/infant and maternal death, respectively. Women aged 45-49 years had the higher rate of maternal, fetal, neonatal and infant mortality. The risk of fetal, neonatal and infant mortality doubled from 40-44 years onwards, and maternal mortality from the age of 30-34 years. Conclusions: Our results suggest that the maternal age range with the lesser general reproductive risk is between 20-29 years. This finding should be considered in future studies of reproductive risk and for an appropriate counseling about conception.

A Population-Based Cohort Study of Breastfeeding According to Gestational Age at Term Delivery

OBJECTIVE Because breastfeeding is the optimal form of infant feeding, this study was conducted to determine the effect of gestational age on breastfeeding in term infants. STUDY DESIGN A retrospective population-based cohort study of singleton/twin hospital births was conducted in Ontario, Canada between April 1, 2009, and March 31, 2010. Multivariate logistic regression was used to determine the adjusted effect of gestational age on breastfeeding. RESULTS Our study population comprised 92,364 infants, of whom 80,297 (86.9%) were exclusively or partially breastfed at the time of hospital discharge. Multivariate logistic regression analyses demonstrated that early-term infants had lower odds of being breastfed compared with infants born at 41 weeks gestation (40 weeks: aOR, 0.93; 95% CI, 0.86-0.99; 39 weeks: aOR, 0.87; 95% CI, 0.81-0.93; 38 weeks: aOR, 0.81; 95% CI, 0.75-0.88; 37 weeks: aOR, 0.74; 95% CI, 0.67-0.82). CONCLUSION Using a population-based approach, we found that infants born at 40, 39, 38, and 37 weeks gestation had increasingly lower odds of being breastfed compared with infants born at 41 weeks. Clinicians need to be made aware of the differences in outcomes of infants delivered at early and late term, so that appropriate breastfeeding support can be provided to women at risk for not breastfeeding.

Preterm birth prevention in twin pregnancies with progesterone, pessary, or cerclage: a systematic review and meta-analysis

About half of twin pregnancies deliver preterm, and it is unclear whether any intervention reduces this risk.

Odds ratio: aspectos teóricos y prácticos

Resumen Odds Ratio (OR) es una medida de efecto comunmente utilizada para comunicar los resultados de una investigacion en salud. Matematicamente un OR corresponde a un cociente entre dos odds, siendo un odds una forma alternativa de expresar la posibilidad de ocurrencia de un evento de interes o de presencia de una exposicion. Desde un punto de vista metodologico, los OR pueden ser calculados en disenos pros-pectivos, retrospectivos y transversales, y bajo ciertas condiciones pueden reemplazar al Riesgo Relativo. En base a una serie de preguntas y ejemplos, el presente articulo explica los fundamentos matematicos y metodologicos subyacentes al concepto de OR, con el objetivo de facilitar su interpretacion a clinicos e investigadores. 1 Unidad de Medicina Basada en Evidencia. 2 Departamento de Salud Publica. 3 Division de Obstetricia y Ginecologia. 4 Departamento de Medicina Interna. Facultad de Medicina, Pontificia Universidad Catolica de Chile. Santiago de Chile.Los autores declararon no tener conflictos de intereses en este manuscrito.Recibido el 4 de enero de 2013, aceptado el 2 de mayo de 2013.Correspondencia a:Dr. Jaime Cerda.Departamento de Salud Publica, Facultad de Medicina, Pontificia Universidad Catolica de Chile. Marcoleta 434, Piso 1. Santiago Centro.Telefono: (56-2) 354-3038E-mail: jcerda@med.puc.cl

Aumento de la mortalidad infantil en niños con síndrome de Down: Chile 1997-2013

BACKGROUND Down syndrome (DS) is associated with higher child mortality especially due to cardiac malformations. AIM To describe the trend in Chilean infant mortality in DS in the period 1997-2013 as compared to the general population without DS. MATERIAL AND METHODS Raw data on infant deaths were extracted from the yearbooks of vital statistics of the National Institute of Statistics. The mortality risk associated to DS, relative to population without DS was estimated. RESULTS There were 456 deaths in infants with DS during the study period (59 early neonatal deaths, 70 late neonatal deaths and 327 post-neonatal deaths). The trend in infant mortality rate in DS was ascending (r: 0.53, p = 0.03), with an average annual percentage change of 4.6% (95% confidence interval (CI) 0.4-9.0%; p < 0.01). Compared to the population without DS, the risk of early neonatal death was lower in DS (Odds ratio (OR) 0.14, 95% CI 0.11-0.19; p < 0.01) whereas the risk of post-neonatal death was higher (OR 4.74, 95% CI 3.85-5.85; p < 0.01). CONCLUSIONS Infant mortality in Down syndrome has an increasing trend. We postulate that these children are not accessing timely cardiac surgery, the main therapeutic tool to reduce the death risk in the first year of life.Background: Down syndrome (DS) is associated with higher child mortality especially due to cardiac malformations. Aim: To describe the trend in Chilean infant mortality in DS in the period 1997-2013 as compared to the general population without DS. Material and methods: Raw data on infant deaths were extracted from the yearbooks of vital statistics of the National Institute of Statistics. The mortality risk associated to SD, relative to population without SD was estimated. Results: There were 456 deaths in infants with DS during the study period (59 early neonatal deaths, 70 late neonatal deaths and 327 post-neonatal deaths). The trend in infant mortality rate in DS was ascending (r: 0.53, p=0.03), with an average annual percentage change of 4.6% (95% confidence interval (CI) 0.4 - 9.0%; p <0.01). Compared to the population without SD, the risk of early neonatal death was lower in DS (Odds ratio (OR) 0.14, 95% CI 0.11-0.19; p<0.01) whereas the risk of post-neonatal death was higher (OR 4.74, 95%CI 3.85- 5.85; p<0.01). Conclusions: Infant mortality in Down syndrome has an increasing trend. We postulate that these children are not accessing timely cardiac surgery, the main therapeutic tool to reduce the death risk in the first year of life.