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Biomedical subjects

R W Platt

Publications and source records attributed to R W Platt.

18 recordsLinked to original sources

Does previous infection protect against atopic eczema and recurrent wheeze in infancy?

BACKGROUND: Frequent infection in infancy and early childhood has been hypothesized to explain the low prevalence of asthma and other atopic disease among children in developing countries (the so-called 'hygiene hypothesis'), but the low prevalence in Eastern Europe remains unexplained. OBJECTIVE: To test the hygiene hypothesis in the Republic of Belarus by examining the relationship between gastrointestinal (GI) and respiratory infection and two potentially atopic outcomes in the first 12 months of life: atopic eczema and recurrent wheeze. METHODS; We carried out two case-control studies nested within a large (n=17 046) randomized trial in Belarus, with cases defined as (1) first occurrence of atopic eczema (n=819) and (2) second episode of wheezing (n=112). Incidence density sampling was used to select four matched controls born within 1 month at the same hospital as the case. Exposure was defined as one or more episodes of GI or respiratory infection (examined separately) with onset >7 days before onset of the case's atopic outcome. Analyses controlled for family atopic history, duration of exclusive breastfeeding, sex, birth weight, maternal education, and (for recurrent wheeze) maternal smoking. RESULTS: For atopic eczema, prior GI infection occurred in 7.4% of cases vs. 6.0% of controls [adjusted OR=1.27 (0.94-1.72)] and prior respiratory infection in 35.2% vs. 32.6% [adjusted OR=1.14 (95% CI=0.94-1.37)]. For recurrent wheeze, prior GI infection occurred in 9.8% of cases vs. 7.4% of controls [adjusted OR=1.30 (0.60-2.82)]. CONCLUSION: Our results do not support the hypothesis that infection protects against atopic eczema or recurrent wheezing in the first 12 months of life.

Adult↗

Quality of information on risk factors reported by ski patrols.

OBJECTIVE: To determine the reliability of reporting of information on risk factors from a standard accident report form used by ski patrols and a follow up mail questionnaire or telephone interview among injured skiers and snowboarders. SETTING: 19 ski areas in the Canadian province of Quebec between November 2001 and April 2002. PARTICIPANTS: 4377 injured skiers and snowboarders seen by the ski patrol, who completed a follow up mail questionnaire or telephone interview. MAIN OUTCOME MEASURES: Kappa and weighted kappa statistics were used to measure the chance corrected agreement for self reported ability, age, skiing time on day of injury, lessons, type of practice, use of helmet at time of injury, and hill difficulty. RESULTS: The kappa value for helmet use at the time of injury was 0.88 (95% confidence interval 0.87 to 0.90) and for other risk factors ranged from 0.45 (skiing time on day of injury) to 0.98 (age). Few differences were seen in reporting by body region of injury. Reporting consistency was lower for respondents who completed telephone interviews compared with those who completed mail questionnaires and those who responded more than four months after the injury. CONCLUSIONS: Moderate to almost perfect agreement, depending on the risk factor, exists between ski patrols' accident report forms and follow up information. Ski patrol reports can be a reliable and readily available source of information on risk factors for skiing and snowboarding.

Adolescent↗

Detecting and eliminating erroneous gestational ages: a normal mixture model.

In perinatal research and clinical practice, gestational age is a crucial variable for measuring foetal 'growth' (birth weight for gestational age) and for estimating the risk of mortality and morbidity, yet reported gestational age values are affected by random and systematic errors due to the absence of a gold standard measure. Previous investigators have used birth weight (which is measured with greater validity and precision than is gestational age) to correct such errors, but existing methods are inadequate due to unreasonable assumptions about the distributions of birth weight and gestational age. We propose a new method for identifying and correcting implausible observations using the expectation-maximization (EM) algorithm. Using population-based data from U.S. birth certificates, we compare the resulting gestational ages, birth weight distributions at each gestational age, and gestational age-specific infant mortality based on the new method with those on the same population produced by previous published correction methods. The new method gives the best birth weight distributions for gestational age and the most realistic gestational-age-specific mortality rates, while each of the other methods has at least one significant flaw.

Algorithms↗

Implausible birth weight for gestational age.

Various rules have been proposed to identify and exclude live births with implausible values of birth weight for gestational age from large perinatal data sets. The authors carried out a preliminary evaluation of common rules by examining the frequency and nature of rule-based exclusions among live births in Canada (excluding Ontario) between 1992 and 1994. There were 625 (0.09%), 133 (0.02%), 170 (0.02%), and 2,858 (0.40%) live births identified for exclusion by a median birth weight for gestational age +/-4 standard deviations (SD) rule, a +/-5 SD rule, a rule based on expert clinical opinion, and a modification of Tukey's rule, respectively. The birth weight and gestational age distribution of the exclusions depended on the particular rule used; for example, 12.1% and 0.3% of live births of > or =4,500 g were excluded under Tukey's rule and the rule based on expert opinion, respectively. Infant mortality rates among those excluded were 8-13 times higher than among all live births. Current rules for identifying implausible birth weight for gestational age tend to flag live births at high risk for infant death. Such rules may erroneously attenuate temporal trends in important perinatal outcomes.

Algorithms↗

Socio-economic disparities in preterm birth: causal pathways and mechanisms.

Preterm birth is the leading cause of infant mortality in industrialised societies. Its incidence is greatly increased among the socially disadvantaged, but the reasons for this excess are unclear and have been relatively unexplored. We hypothesise two distinct sets of causal pathways and mechanisms that may explain social disparities in preterm birth. The first set involves chronic and acute psychosocial stressors, psychological distress caused by those stressors, increased secretion of placental corticotropin releasing hormone (CRH), changes in sexual behaviours or enhanced susceptibility to bacterial vaginosis and chorioamnionitis, cigarette smoking or cocaine use, and decidual vasculopathy. The second hypothesised pathway is a gene-environment interaction based on a highly prevalent mutation in the gene for methylenetetrahydrofolate reductase (MTHFR), combined with low folate intake from the diet and from prenatal vitamin supplements, consequent hyperhomocysteinemia, and decidual vasculopathy. We propose to test these hypothesised pathways and mechanisms in a nested case-control study within a prospectively recruited and followed cohort of pregnant women with singleton pregnancies who deliver at one of four Montreal hospitals that serve an ethnically and socio-economically diverse population. Following recruitment during the late first or early second trimester, participating women are seen at 24-26 weeks, when a research nurse obtains a detailed medical and obstetric history; administers several scales to assess chronic and acute stressors and psychological function; obtains blood samples for CRH, red blood cell and plasma folate, homocysteine, and DNA for the MTHFR mutation; and performs a digital and speculum examination to measure cervical length and vaginal pH and to obtain swabs for bacterial vaginosis and fetal fibronectin. After delivery, each case (delivery at < 37 completed weeks following spontaneous onset of labour or prelabour rupture of membranes) and two controls are selected for placental pathological examination, hair analysis of cotinine, cocaine, and benzoylecgonine, and analysis of stored blood and vaginal specimens. Statistical analysis will be based on multiple logistic regression and structural equation modelling, with sequential construction of models of potential aetiological determinants and covariates to test the hypothesised causal pathways and mechanisms. The research we propose should improve understanding of the factors and processes that mediate social disparities in preterm birth. This improved understanding should help not only in developing strategies to reduce the disparities but also in suggesting preventive interventions applicable across the entire socio-economic spectrum.

Adult↗

Dystocia among women with symptomatic uterine rupture.

OBJECTIVE: The purpose of this study was to analyze cervical dilatation patterns among women with uterine rupture by means of a mathematic model and to use the results to determine optimal intervention criteria. STUDY DESIGN: This was a case-control review that compared a case patient group of 19 women with uterine rupture during labor with control groups with either no previous cesarean deliveries, vaginal birth after cesarean delivery, or failure of attempted vaginal birth after cesarean delivery. The mathematic model quantified dilatation and adjusted for conditions specific to each patient. Case patients were compared with matched control subjects by means of paired t tests, analysis of variance, odds ratios, and conditional logistic regression. RESULTS: Dystocia was present in 31.6% to 47.4% of patients with uterine rupture, versus 2.6% to 13.2% of the control group with no previous cesarean deliveries (P< or =.001). The incidence of an arrest disorder among patients with uterine rupture was similar to that seen in the control group with failure of attempted vaginal birth after cesarean delivery. However, the interval from diagnosis to rupture or cesarean delivery was 5.5 +/- 3.3 hours among case patients with uterine rupture and 1.5 +/- 1.3 hours in the control group with failure of attempted vaginal birth after cesarean delivery. CONCLUSION: When cervical dilatation was lower than the 10th percentile and was arrested for > or =2 hours, cesarean delivery would have prevented 42.1% of the cases of uterine rupture and resulted in excess 2.6% and 7.9% cesarean delivery rates among women with no previous cesarean deliveries and women with vaginal birth after cesarean delivery, respectively.

Case-Control Studies↗

A new and improved population-based Canadian reference for birth weight for gestational age.

BACKGROUND: Existing fetal growth references all suffer from 1 or more major methodologic problems, including errors in reported gestational age, biologically implausible birth weight for gestational age, insufficient sample sizes at low gestational age, single-hospital or other non-population-based samples, and inadequate statistical modeling techniques. METHODS: We used the newly developed Canadian national linked file of singleton births and infant deaths for births between 1994 and 1996, for which gestational age is largely based on early ultrasound estimates. Assuming a normal distribution for birth weight at each gestational age, we used the expectation-maximization algorithm to exclude infants with gestational ages that were more consistent with 40-week births than with the observed gestational age. Distributions of birth weight at the corrected gestational ages were then statistically smoothed. RESULTS: The resulting male and female curves provide smooth and biologically plausible means, standard deviations, and percentile cutoffs for defining small- and large-for-gestational-age births. Large-for-gestational age cutoffs (90th percentile) at low gestational ages are considerably lower than those of existing references, whereas small-for-gestational-age cutoffs (10th percentile) postterm are higher. For example, compared with the current World Health Organization reference from California (Williams et al, 1982) and a recently proposed US national reference (Alexander et al, 1996), the 90th percentiles for singleton males at 30 weeks are 1837 versus 2159 and 2710 g. The corresponding 10th percentiles at 42 weeks are 3233 versus 3086 and 2998 g. CONCLUSIONS: This new sex-specific, population-based reference should improve clinical assessment of growth in individual newborns, population-based surveillance of geographic and temporal trends in birth weight for gestational age, and evaluation of clinical or public health interventions to enhance fetal growth. fetal growth, birth weight, gestational age, preterm birth, postterm birth.

Algorithms↗

Maternal smoking and the risk of early weaning: a meta-analysis.

OBJECTIVES: This study reviewed evidence on the effect of maternal smoking on early weaning. METHODS: The following databases and journals were searched: Medline, Scientific Citation Index, Pediatrics, Journal of Pediatrics, New England Journal of Medicine, and Lancet. Analysis was restricted to studies in which infants who had never been breastfed were excluded or the prevalence of breastfeeding initiation was more than 90%. RESULTS: In smoking vs nonsmoking mothers, the random effects odds ratio for weaning before 3 months was 1.93 (95% confidence interval [CI] = 1.55, 2.40). An adjusted odds ratio of 1.50 (95% CI = 1.34, 1.68) was shown in studies that had lost-to-follow-up rates below 15% and included adequate adjustment for confounding. CONCLUSIONS: Maternal smoking increases the risk of early weaning.

Adult↗

The contribution of mild and moderate preterm birth to infant mortality. Fetal and Infant Health Study Group of the Canadian Perinatal Surveillance System.

CONTEXT: The World Health Organization defines preterm birth as birth at less than 37 completed gestational weeks, but most studies have focused on very preterm infants (birth at <32 weeks) because of their high risk of mortality and serious morbidity. However, infants born at 32 through 36 weeks are more common and their public health impact has not been well studied. OBJECTIVE: To assess the quantitative contribution of mild (birth at 34-36 gestational weeks) and moderate (birth at 32-33 gestational weeks) preterm birth to infant mortality. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study using linked singleton live birth-infant death cohort files for US birth cohorts for 1985 and 1995 and Canadian birth cohorts (excluding Ontario) for 1985-1987 and 1992-1994. MAIN OUTCOME MEASURES: Relative risks (RRs) and etiologic fractions (EFs) for overall and cause-specific early neonatal (age 0-6 days), late neonatal (age 7-27 days), postneonatal (age 28-364 days), and total infant death among mild and moderate preterm births vs term births (at >/=37 gestational weeks). RESULTS: Relative risks for infant death from all causes among singletons born at 32 through 33 gestational weeks were 6.6 (95% confidence interval [CI], 6.1-7.0) in the United States in 1995 and 15.2 (95% CI, 13.2-17.5) in Canada in 1992-1994; among singletons born at 34 through 36 gestational weeks, the RRs were 2.9 (95% CI, 2.8-3.0) and 4.5 (95% CI, 4.0-5.0), respectively. Corresponding EFs were 3.2% and 4.8%, respectively, at 32 through 33 gestational weeks and 6.3% and 8.0%, respectively, at 34 through 36 gestational weeks; the sum of the EFs for births at 32 through 33 and 34 through 36 gestational weeks exceeded those for births at 28 through 31 gestational weeks. Substantial RRs were observed overall for the neonatal (eg, for early neonatal deaths, 14.6 and 33.0 for US and Canadian infants, respectively, born at 32-33 gestational weeks; EFs, 3.6% and and 6. 2% for US and Canadian infants, respectively) and postneonatal (RRs, 2.1-3.8 and 3.0-7.0 for US and Canadian infants, respectively, born at 32-36 gestational weeks; EFs, 2.7%-5.8% and 3.0%-7.0% for the same groups, respectively) periods and for death due to asphyxia, infection, sudden infant death syndrome, and external causes. Except for a reduction in the RR and EF for neonatal mortality due to infection, the patterns have changed little since 1985 in either country. CONCLUSIONS: Mild- and moderate-preterm birth infants are at high RR for death during infancy and are responsible for an important fraction of infant deaths. JAMA. 2000;284:843-849

Canada↗

Bootstrap confidence intervals for the sensitivity of a quantitative diagnostic test.

We examine bootstrap approaches to the analysis of the sensitivity of quantitative diagnostic test data. Methods exist for inference concerning the sensitivity of one or more tests for fixed levels of specificity, taking into account the variability in the sensitivity due to variability in the test values for normal subjects. However, parametric methods do not adequately account for error, particularly when the data are non-normally distributed, and non-parametric methods have low power. We implement bootstrap methods for confidence limits for the sensitivity of a test for a fixed specificity and demonstrate that under certain circumstances the bootstrap method gives more accurate confidence intervals than do other methods, while it performs at least as well as other methods in many standard situations.

Algorithms↗

Saddlepoint approximations for small sample logistic regression problems.

Double saddlepoint approximations provide quick and accurate approximations to exact conditional tail probabilities in a variety of situations. This paper describes the use of these approximations in two logistic regression problems. An investigation of regression analysis of the log-odds ratio in a sequence or set of 2x2 tables via simulation studies shows that in practical settings the saddlepoint methods closely approximate exact conditional inference. The double saddlepoint approximation in the test for trend in a sequence of binomial random variates is also shown, via simulation studies, to be an effective approximation to exact conditional inference.

Logistic Models↗

Generalized linear mixed models for meta-analysis.

We examine two strategies for meta-analysis of a series of 2 x 2 tables with the odds ratio modelled as a linear combination of study level covariates and random effects representing between-study variation. Penalized quasi-likelihood (PQL), an approximate inference technique for generalized linear mixed models, and a linear model fitted by weighted least squares to the observed log-odds ratios are used to estimate regression coefficients and dispersion parameters. Simulation results demonstrate that both methods perform adequate approximate inference under many conditions, but that neither method works well in the presence of highly sparse data. Under certain conditions with small cell frequencies the PQL method provides better inference.

Humans↗

How small is too small in a twin pregnancy?

OBJECTIVE: The objective was to determine whether small twins had a survival advantage with respect to small singletons after controlling for other factors associated with adverse perinatal outcome. STUDY DESIGN: A hospital-based cohort study included all births between 1980 and 1995 of babies born between 24 and 43 weeks' gestation. Logistic regression was used to estimate the perinatal mortality risks for monochorionic and dichorionic twins with growth restriction after adjusting for gestational age, maternal age, parity, method of delivery, and the presence or absence of congenital malformations. RESULTS: The study sample included 1062 dichorionic twins, 354 monochorionic twins, and 59,873 singletons. Small monochorionic and dichorionic twins showed a similar overall risk of perinatal mortality (odds ratio 1.40, confidence interval 0.86 to 2.25). However, monochorionic twins with birth weights <10th percentile faced an increased risk of perinatal death compared with singletons (odds ratio 2.45, confidence interval 1.20 to 5.02). Dichorionic twins had no such increased risk (odds ratio 0.91, confidence interval 0.45 to 1.84). CONCLUSIONS: Twins with growth restriction are not protected against perinatal loss, even after adjusting for congenital malformations. In fact, monochorionic twins are more than twice as likely to die in the perinatal period as are their singleton counterparts.

Cohort Studies↗