Observational analytic studies in multiple sclerosis: controlling bias through study design and conduct. The Australian Multicentre Study of Environment and Immune Function

Rising multiple sclerosis incidence over the last 50 years and geographic patterns of occurrence suggest an environmental role in the causation of this multifactorial disease. Design options for epidemiological studies of environmental causes of multiple sclerosis are limited by the low incidence of the disease, possible diagnostic delay and budgetary constraints. We describe scientific and methodological issues considered in the development of the Australian Multicentre Study of Environment and Immune Function (the Ausimmune Study), which seeks, in particular, to better understand the causes of the well-known MS positive latitudinal gradient. A multicentre, case-control design down the eastern seaboard of Australia allows the recruitment of sufficient cases for adequate study power and provides data on environmental exposures that vary by latitude. Cases are persons with an incident first demyelinating event (rather than prevalent multiple sclerosis), sourced from a population base using a two tier notification system. Controls, matched on sex, age (within two years) and region of residence, are recruited from the general population. Biases common in case-control studies, eg, prevalence-incidence bias, admission-rate bias, non-respondent bias, observer bias and recall bias, as well as confounding have been carefully considered in the study design and conduct of the Ausimmune Study

Childbirth and consequent atopic disease: emerging evidence on epigenetic effects based on the hygiene and EPIIC hypotheses

Background: In most high and middle income countries across the world, at least 1:4 women give birth by cesarean section. Rates of labour induction and augmentation are rising steeply; and in some countries up to 50 % of laboring women and newborns are given antibiotics. Governments and international agencies are increasingly concerned about the clinical, economic and psychosocial effects of these interventions. Discussion: There is emerging evidence that certain intrapartum and early neonatal interventions might affect the neonatal immune response in the longer term, and perhaps trans-generationally. Two theories lead the debate in this area. Those aligned with the hygiene (or ‘Old Friends’) hypothesis have examined the effect of gut microbiome colonization secondary to mode of birth and intrapartum/neonatal pharmacological interventions on immune response and epigenetic phenomena. Those working with the EPIIC (Epigenetic Impact of Childbirth) hypothesis are concerned with the effects of eustress and dys-stress on the epigenome, secondary to mode of birth and labour interventions. Summary: This paper examines the current and emerging findings relating to childbirth and atopic/autoimmune disease from the perspective of both theories, and proposes an alliance of research effort. This is likely to accelerate the discovery of important findings arising from both approaches, and to maximize the timely understanding of the longer-term consequences of childbirth practices

Long-term risks and benefits associated with cesarean delivery for mother, baby, and subsequent pregnancies: Systematic review and meta-analysis

BACKGROUND:Cesarean birth rates continue to rise worldwide with recent (2016) reported rates of 24.5% in Western Europe, 32% in North America, and 41% in South America. The objective of this systematic review is to describe the long-term risks and benefits of cesarean delivery for mother, baby, and subsequent pregnancies. The primary maternal outcome was pelvic floor dysfunction, the primary baby outcome was asthma, and the primary subsequent pregnancy outcome was perinatal death. METHODS AND FINDINGS:Medline, Embase, Cochrane, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases were systematically searched for published studies in human subjects (last search 25 May 2017), supplemented by manual searches. Included studies were randomized controlled trials (RCTs) and large (more than 1,000 participants) prospective cohort studies with greater than or equal to one-year follow-up comparing outcomes of women delivering by cesarean delivery and by vaginal delivery. Two assessors screened 30,327 abstracts. Studies were graded for risk of bias by two assessors using the Scottish Intercollegiate Guideline Network (SIGN) Methodology Checklist and the Risk of Bias Assessment tool for Non-Randomized Studies. Results were pooled in fixed effects meta-analyses or in random effects models when significant heterogeneity was present (I2 ≥ 40%). One RCT and 79 cohort studies (all from high income countries) were included, involving 29,928,274 participants. Compared to vaginal delivery, cesarean delivery was associated with decreased risk of urinary incontinence, odds ratio (OR) 0.56 (95% CI 0.47 to 0.66; n = 58,900; 8 studies) and pelvic organ prolapse (OR 0.29, 0.17 to 0.51; n = 39,208; 2 studies). Children delivered by cesarean delivery had increased risk of asthma up to the age of 12 years (OR 1.21, 1.11 to 1.32; n = 887,960; 13 studies) and obesity up to the age of 5 years (OR 1.59, 1.33 to 1.90; n = 64,113; 6 studies). Pregnancy after cesarean delivery was associated with increased risk of miscarriage (OR 1.17, 1.03 to 1.32; n = 151,412; 4 studies) and stillbirth (OR 1.27, 1.15 to 1.40; n = 703,562; 8 studies), but not perinatal mortality (OR 1.11, 0.89 to 1.39; n = 91,429; 2 studies). Pregnancy following cesarean delivery was associated with increased risk of placenta previa (OR 1.74, 1.62 to 1.87; n = 7,101,692; 10 studies), placenta accreta (OR 2.95, 1.32 to 6.60; n = 705,108; 3 studies), and placental abruption (OR 1.38, 1.27 to 1.49; n = 5,667,160; 6 studies). This is a comprehensive review adhering to a registered protocol, and guidelines for the Meta-analysis of Observational Studies in Epidemiology were followed, but it is based on predominantly observational data, and in some meta-analyses, between-study heterogeneity is high; therefore, causation cannot be inferred and the results should be interpreted with caution. CONCLUSIONS:When compared with vaginal delivery, cesarean delivery is associated with a reduced rate of urinary incontinence and pelvic organ prolapse, but this should be weighed against the association with increased risks for fertility, future pregnancy, and long-term childhood outcomes. This information could be valuable in counselling women on mode of delivery

Asthma and Atopy in Children Born by Caesarean Section: Effect Modification by Family History of Allergies - a Population Based Cross-sectional Study

Background: Studies on the association of birth by caesarean section (C/S) and allergies have produced conflicting findings. Furthermore, evidence on whether this association may differ in those at risk of atopy is limited. This study aims to investigate the association of mode of delivery with asthma and atopic sensitization and the extent to which any effect is modified by family history of allergies.Methods: Asthma outcomes were assessed cross-sectionally in 2216 children at age 8 on the basis of parents' responses to the ISAAC questionnaire whilst skin prick tests to eleven aeroallergens were also performed in a subgroup of 746 children. Adjusted odds ratios of asthma and atopy by mode of delivery were estimated in multivariable logistic models while evidence of effect modification was examined by introducing interaction terms in the models.Results: After adjusting for potential confounders, children born by C/S appeared significantly more likely than those born vaginally to report ever wheezing (OR 1.36, 95% CI 1.07-1.71), asthma diagnosis (OR 1.41, 95% CI 1.09-1.83) and be atopic (OR 1.67, 95% CI 1.08-2.60). There was modest evidence that family history of allergies may modify the effect of C/S delivery on atopy (p for effect modification=0.06) but this was not the case for the asthma outcomes. Specifically, while more than a two-fold increase in the odds of being a topic was observed in children with a family history of allergies if born by C/S (OR 2.62, 95% CI 1.38-5.00), no association was observed in children without a family history of allergies (OR 1.16, 95% CI 0.64-2.11).Conclusions: Birth by C/S is associated with asthma and atopic sensitization in childhood. The association of C/S and atopy appears more pronounced in children with family history of allergies

Французский язык

Пособие состоит из 7 разделов, первые 5 из которых включают необходимый грамматический материал для продуктивного усвоения и завершаются тренировочными упражнениями и заданиями. В разделе 6 размещены ключи к тренировочным упражнениям и заданиям; раздел 7 содержит примерный контрольный лексико-грамматический тест, ключи к нему и шкалу оценки результатов выполнения теста. Практикум по дисциплине «Иностранный язык» для студентов экономических специальностей заочной формы обучения