540 research outputs found

    Timing of birth for women with a twin pregnancy at term: a randomised controlled trial

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    <p>Abstract</p> <p>Background</p> <p>There is a well recognized risk of complications for both women and infants of a twin pregnancy, increasing beyond 37 weeks gestation. Preterm birth prior to 37 weeks gestation is a recognized complication of a twin pregnancy, however, up to 50% of twins will be born after this time.</p> <p>The aims of this randomised trial are to assess whether elective birth at 37 weeks gestation compared with standard care in women with a twin pregnancy affects the risk of perinatal death, and serious infant complications.</p> <p>Methods/Design</p> <p>Design: Multicentred randomised trial.</p> <p>Inclusion Criteria: women with a twin pregnancy at 36<sup>6 </sup>weeks or more without contraindication to continuation of pregnancy.</p> <p>Trial Entry & Randomisation: Following written informed consent, eligible women will be randomised from 36<sup>+6 </sup>weeks gestation. The randomisation schedule uses balanced variable blocks, with stratification for centre of birth and planned mode of birth. Women will be randomised to either elective birth or standard care.</p> <p>Treatment Schedules: Women allocated to the elective birth group will be planned for elective birth from 37 weeks gestation. Where the plan is for vaginal birth, this will involve induction of labour. Where the plan is for caesarean birth, this will involve elective caesarean section. For women allocated to standard care, birth will be planned for 38 weeks gestation or later. Where the plan is for vaginal birth, this will involve either awaiting the spontaneous onset of labour, or induction of labour if required. Where the plan is for caesarean birth, this will involve elective caesarean section (after 38 and as close to 39 weeks as possible).</p> <p>Primary Study Outcome: A composite of perinatal mortality or serious neonatal morbidity.</p> <p>Sample Size: 460 women with a twin pregnancy to show a reduction in the composite outcome from 16.3% to 6.7% with adjustment for the clustering of twin infants within mothers (p = 0.05, 80% power).</p> <p>Discussion</p> <p>This is a protocol for a randomised trial, the findings of which will contribute information about the optimal time of birth for women with an uncomplicated multiple pregnancy at and beyond 37 weeks gestation.</p> <p>Clinical Trial Registration</p> <p>Current Controlled Trials ISRCTN15761056</p

    Individual Exposure to NO2 in Relation to Spatial and Temporal Exposure Indices in Stockholm, Sweden: The INDEX Study

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    Epidemiology studies of health effects from air pollution, as well as impact assessments, typically rely on ambient monitoring data or modelled residential levels. The relationship between these and personal exposure is not clear. To investigate personal exposure to NO2 and its relationship with other exposure metrics and time-activity patterns in a randomly selected sample of healthy working adults (20–59 years) living and working in Stockholm. Personal exposure to NO2 was measured with diffusive samplers in sample of 247 individuals. The 7-day average personal exposure was 14.3 µg/m3 and 12.5 µg/m3 for the study population and the inhabitants of Stockholm County, respectively. The personal exposure was significantly lower than the urban background level (20.3 µg/m3). In the univariate analyses the most influential determinants of individual exposure were long-term high-resolution dispersion-modelled levels of NO2 outdoors at home and work, and concurrent NO2 levels measured at a rural location, difference between those measured at an urban background and rural location and difference between those measured in busy street and at an urban background location, explaining 20, 16, 1, 2 and 4% (R2) of the 7-day personal NO2 variation, respectively. A regression model including these variables explained 38% of the variation in personal NO2 exposure. We found a small improvement by adding time-activity variables to the latter model (R2 = 0.44). The results adds credibility primarily to long-term epidemiology studies that utilise long-term indices of NO2 exposure at home or work, but also indicates that such studies may still suffer from exposure misclassification and dilution of any true effects. In contrast, urban background levels of NO2 are poorly related to individual exposure

    Exploring Variation and Predictors of Residential Fine Particulate Matter Infiltration

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    Although individuals spend the majority of their time indoors, most epidemiological studies estimate personal air pollution exposures based on outdoor levels. This almost certainly results in exposure misclassification as pollutant infiltration varies between homes. However, it is often not possible to collect detailed measures of infiltration for individual homes in large-scale epidemiological studies and thus there is currently a need to develop models that can be used to predict these values. To address this need, we examined infiltration of fine particulate matter (PM2.5) and identified determinants of infiltration for 46 residential homes in Toronto, Canada. Infiltration was estimated using the indoor/outdoor sulphur ratio and information on hypothesized predictors of infiltration were collected using questionnaires and publicly available databases. Multiple linear regression was used to develop the models. Mean infiltration was 0.52 ± 0.21 with no significant difference across heating and non-heating seasons. Predictors of infiltration were air exchange, presence of central air conditioning, and forced air heating. These variables accounted for 38% of the variability in infiltration. Without air exchange, the model accounted for 26% of the variability. Effective modelling of infiltration in individual homes remains difficult, although key variables such as use of central air conditioning show potential as an easily attainable indicator of infiltration

    Cardiovascular diseases and air pollution in Novi Sad, Serbia

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    Objectives: A large body of evidence has documented that air pollutants have adverse effect on human health as well as on the environment. The aim of this study was to determine whether there was an association between outdoor concentrations of sulfur dioxide (SO2) and nitrogen dioxide (NO2) and a daily number of hospital admissions due to cardiovascular diseases (CVD) in Novi Sad, Serbia among patients aged above 18. Material and Methods: The investigation was carried out during over a 3-year period (from January 1, 2007 to December 31, 2009) in the area of Novi Sad. The number (N = 10 469) of daily CVD (ICD-10: I00-I99) hospital admissions was collected according to patients' addresses. Daily mean levels of NO2 and SO2, measured in the ambient air of Novi Sad via a network of fixed samplers, have been used to put forward outdoor air pollution. Associations between air pollutants and hospital admissions were firstly analyzed by the use of the linear regression in a single polluted model, and then trough a single and multi-polluted adjusted generalized linear Poisson model. Results: The single polluted model (without confounding factors) indicated that there was a linear increase in the number of hospital admissions due to CVD in relation to the linear increase in concentrations of SO2 (p = 0.015; 95% confidence interval (95% CI): 0.144-1.329, R2 = 0.005) and NO2 (p = 0.007; 95% CI: 0.214-1.361, R2 = 0.007). However, the single and multi-polluted adjusted models revealed that only NO2 was associated with the CVD (p = 0.016, relative risk (RR) = 1.049, 95% CI: 1.009-1.091 and p = 0.022, RR = 1.047, 95% CI: 1.007-1.089, respectively). Conclusions: This study shows a significant positive association between hospital admissions due to CVD and outdoor NO2 concentrations in the area of Novi Sad, Serbia

    Toward a better definition of focal cortical dysplasia: An iterative histopathological and genetic agreement trial

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    Objective: Focal cortical dysplasia (FCD) is a major cause of difficult-to-treat epilepsy in children and young adults, and the diagnosis is currently based on microscopic review of surgical brain tissue using the International League Against Epilepsy classification scheme of 2011. We developed an iterative histopathological agreement trial with genetic testing to identify areas of diagnostic challenges in this widely used classification scheme. Methods: Four web-based digital pathology trials were completed by 20 neuropathologists from 15 countries using a consecutive series of 196 surgical tissue blocks obtained from 22 epilepsy patients at a single center. Five independent genetic laboratories performed screening or validation sequencing of FCD-relevant genes in paired brain and blood samples from the same 22 epilepsy patients. Results: Histopathology agreement based solely on hematoxylin and eosin stainings was low in Round 1, and gradually increased by adding a panel of immunostainings in Round 2 and the Delphi consensus method in Round 3. Interobserver agreement was good in Round 4 (kappa&nbsp;=.65), when the results of genetic tests were disclosed, namely, MTOR, AKT3, and SLC35A2 brain somatic mutations in five cases and germline mutations in DEPDC5 and NPRL3 in two cases. Significance: The diagnoses of FCD 1 and 3 subtypes remained most challenging and were often difficult to differentiate from a normal homotypic or heterotypic cortical architecture. Immunohistochemistry was helpful, however, to confirm the diagnosis of FCD or no lesion. We observed a genotype–phenotype association for brain somatic mutations in SLC35A2 in two cases with mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy. Our results suggest that the current FCD classification should recognize a panel of immunohistochemical stainings for a better histopathological workup and definition of FCD subtypes. We also propose adding the level of genetic findings to obtain a comprehensive, reliable, and integrative genotype–phenotype diagnosis in the near future

    Mitochondrial ATP synthase inhibition and nitric oxide are involved in muscle weakness that occurs in acute exposure of rats to monocrotophos

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    Organophosphate poisoning in the context of self-harm is a common medical emergency in Asia. Prolonged muscle weakness is an important but poorly understood cause of morbidity and mortality of the poisoning. This study examined mitochondrial function and its modulation by nitric oxide in muscle weakness of rats exposed to an acute, oral (0.8LD50) dose of monocrotophos. Muscle mitochondrial ATP synthase activity was inhibited in the rat in acute exposure to monocrotophos while respiration per se was not affected. This was accompanied by decreased mitochondrial uptake of calcium and increased levels of nitric oxide. Reactive cysteine groups of ATP synthase subunits were reduced in number, which may contribute to decreased enzyme activity. The decrease in ATP synthase activity and reactive cysteine groups of ATP synthase subunits was prevented by treatment of animals with the nitric oxide synthase inhibitor, L-NG Nitroarginine methyl ester, at 12 mg/kg body weight for 9 days in drinking water, prior to monocrotophos exposure. This indicated a role for nitric oxide in the process. The alterations in mitochondrial calcium uptake may influence cytosolic calcium levels and contribute to muscle weakness of acute organophosphate exposure

    Residential Proximity to a Major Roadway Is Associated with Features of Asthma Control in Children

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    BACKGROUND: While several studies suggest that traffic-related air pollutants are detrimental for respiratory health, few studies have examined relationships between residential proximity to a major roadway and asthma control in children. Furthermore, a major limitation of existing research is reliance on self-reported outcomes. We therefore determined the spatial relationship between the distance from a major roadway and clinical, physiologic and inflammatory features of asthma in a highly characterized sample of asthmatic children 6-17 years of age across a wide range of severities. We hypothesized that a closer residential proximity to a major roadway would be associated with increased respiratory symptoms, altered pulmonary function and a greater magnitude of airway and systemic inflammation. METHODOLOGY/PRINCIPAL FINDINGS: 224 children 6-17 years with confirmed asthma completed questionnaires and underwent spirometry, plethysmography, exhaled nitric oxide determination, exhaled breath condensate collection and venipuncture. Residential distance from a major roadway was determined by mapping the geographic coordinates of the residential address in Geographic Information System software. The distance between the home address and the nearest major roadway was calculated according to the shortest distance between the two points (i.e., "as the crow flies"). Asthmatic children living in closer proximity to a major roadway had an increased frequency of wheezing associated with increased medication requirements and more hospitalizations even after controlling for potential confounders. These children also had increased airway resistance, increased airway inflammation reflected by a lower breath condensate pH, and higher plasma EGF concentrations. CONCLUSIONS/SIGNIFICANCE: These findings suggest that closer residential proximity to a major roadway is associated with poorer asthma control in school-age children. Assessment of residential proximity to major roadways may be useful in the clinical evaluation of asthma in children
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