Trial of labour after caesarean section and the risk of neonatal and infant death: a nationwide cohort study

Background: Caesarean section (CS) rates are increasing worldwide and as a result repeat CS is common. The optimal mode of delivery in women with one previous CS is widely debated and the risks to the infant are understudied. The aim of the current study was to evaluate if women with a trial of labour after caesarean (TOLAC) had an increased odds of neonatal and infant death compared to women with an elective repeat CS (ERCS). Methods: A population register-based cohort study was conducted in Denmark between 1982 and 2010. All women with two deliveries [in which the first was a CS, and the second was an uncomplicated, term delivery (n = 61,626)] were included in the study. Logistic regression models were used to report adjusted odds ratios (AOR) and 95% confidence intervals (CI) of the odds of death according to mode of delivery. The main outcome measures were neonatal death (early and late) and infant death. Results: Women with a TOLAC had an increased odds of neonatal death (AOR 1 · 87, 95% CI 1 · 12 to 3 · 12) due to an increased risk of early neonatal death (AOR 2 · 06, 95% CI 1 · 19 to 3 · 56) and no effect on late neonatal death (AOR 0 · 97, 95% CI 0 · 22 to 4 · 32), or infant death (AOR 1 · 12, 95% CI 0 · 79 to 1 · 59) when compared to the reference group of women with an ERCS. There was evidence of a cohort effect as the increased odds of neonatal death (AOR 3 · 89, 95% CI 1 · 33 to 11 · 39) was most significant in the earlier years (1982–1991) and gradually disappeared (AOR 1 · 01, 95% CI 0 · 44 to 2 · 31) in the later years (2002–2010). Conclusions: Although an increased risk of neonatal death was found in women with a TOLAC, there was evidence of a cohort effect, which showed this increased odds disappearing over time. Advances in modern healthcare including improved monitoring and earlier detection of underlying pregnancy complications may explain the findings

Cesarean section and rate of subsequent stillbirth, miscarriage and ectopic pregnancy: a Danish register-based cohort study

Background: With cesarean section rates increasing worldwide, clarity regarding negative effects is essential. This study aimed to investigate the rate of subsequent stillbirth, miscarriage, and ectopic pregnancy following primary cesarean section, controlling for confounding by indication. Methods and Findings: We performed a population-based cohort study using Danish national registry data linking various registers. The cohort included primiparous women with a live birth between January 1, 1982, and December 31, 2010 (n = 832,996), with follow-up until the next event (stillbirth, miscarriage, or ectopic pregnancy) or censoring by live birth, death, emigration, or study end. Cox regression models for all types of cesarean sections, sub-group analyses by type of cesarean, and competing risks analyses for the causes of stillbirth were performed. An increased rate of stillbirth (hazard ratio [HR] 1.14, 95% CI 1.01, 1.28) was found in women with primary cesarean section compared to spontaneous vaginal delivery, giving a theoretical absolute risk increase (ARI) of 0.03% for stillbirth, and a number needed to harm (NNH) of 3,333 women. Analyses by type of cesarean section showed similarly increased rates for emergency (HR 1.15, 95% CI 1.01, 1.31) and elective cesarean (HR 1.11, 95% CI 0.91, 1.35), although not statistically significant in the latter case. An increased rate of ectopic pregnancy was found among women with primary cesarean overall (HR 1.09, 95% CI 1.04, 1.15) and by type (emergency cesarean, HR 1.09, 95% CI 1.03, 1.15, and elective cesarean, HR 1.12, 95% CI 1.03, 1.21), yielding an ARI of 0.1% and a NNH of 1,000 women for ectopic pregnancy. No increased rate of miscarriage was found among women with primary cesarean, with maternally requested cesarean section associated with a decreased rate of miscarriage (HR 0.72, 95% CI 0.60, 0.85). Limitations include incomplete data on maternal body mass index, maternal smoking, fertility treatment, causes of stillbirth, and maternally requested cesarean section, as well as lack of data on antepartum/intrapartum stillbirth and gestational age for stillbirth and miscarriage. Conclusions: This study found that cesarean section is associated with a small increased rate of subsequent stillbirth and ectopic pregnancy. Underlying medical conditions, however, and confounding by indication for the primary cesarean delivery account for at least part of this increased rate. These findings will assist women and health-care providers to reach more informed decisions regarding mode of delivery

Direct hospital costs of chest pain patients attending the emergency department: a retrospective study

BACKGROUND: Chest pain is one of the most common complaints in the Emergency Department (ED), but the cost of ED chest pain patients is unclear. The aim of this study was to describe the direct hospital costs for unselected chest pain patients attending the emergency department (ED). METHODS: 1,000 consecutive ED visits of patients with chest pain were retrospectively included. Costs directly following the ED visit were retrieved from the hospital economy system. RESULTS: The mean cost per patient visit was 26.8 thousand Swedish kronar (kSEK) (median 7.2 kSEK), with admission time accounting for 73% of all costs. Mean cost for patients discharged from the ED was 1.4 kSEK (median 1.3 kSEK), and for patients without ACS admitted 1 day or less 7.6 kSEK (median 6.9 kSEK). The practice in the present study to admit 67% of the patients, of whom only 31% proved to have ACS, was estimated to give a cost per additional life-year saved by hospital admission, compared to theoretical strategy of discharging all patients home, of about 350 kSEK (39 kEUR or 42 kUSD). CONCLUSION: Costs for chest pain patients are large and primarily due to admission time. The present admission practice seems to be cost-effective, but the substantial overadmission indicates that better ED diagnostics and triage could decrease costs considerably

A participatory physical and psychosocial intervention for balancing the demands and resources among industrial workers (PIPPI): study protocol of a cluster-randomized controlled trial

Background: Need for recovery and work ability are strongly associated with high employee turnover, well-being and sickness absence. However, scientific knowledge on effective interventions to improve work ability and decrease need for recovery is scarce. Thus, the present study aims to describe the background, design and protocol of a cluster randomized controlled trial evaluating the effectiveness of an intervention to reduce need for recovery and improve work ability among industrial workers. Methods/Design: A two-year cluster randomized controlled design will be utilized, in which controls will also receive the intervention in year two. More than 400 workers from three companies in Denmark will be aimed to be cluster randomized into intervention and control groups with at least 200 workers (at least 9 work teams) in each group. An organizational resources audit and subsequent action planning workshop will be carried out to map the existing resources and act upon initiatives not functioning as intended. Workshops will be conducted to train leaders and health and safety representatives in supporting and facilitating the intervention activities. Group and individual level participatory visual mapping sessions will be carried out allowing team members to discuss current physical and psychosocial work demands and resources, and develop action plans to minimize strain and if possible, optimize the resources. At all levels, the intervention will be integrated into the existing organization of work schedules. An extensive process and effect evaluation on need for recovery and work ability will be carried out via questionnaires, observations, interviews and organizational data assessed at several time points throughout the intervention period. Discussion: This study primarily aims to develop, implement and evaluate an intervention based on the abovementioned features which may improve the work environment, available resources and health of industrial workers, and hence their need for recovery and work ability

Using Polarized Spectroscopy to Investigate Order in Thin-Films of Ionic Self-Assembled Materials Based on Azo-Dyes

Three series of ionic self-assembled materials based on anionic azo-dyes and cationic benzalkonium surfactants were synthesized and thin films were prepared by spin-casting. These thin films appear isotropic when investigated with polarized optical microscopy, although they are highly anisotropic. Here, three series of homologous materials were studied to rationalize this observation. Investigating thin films of ordered molecular materials relies to a large extent on advanced experimental methods and large research infrastructure. A statement that in particular is true for thin films with nanoscopic order, where X-ray reflectometry, X-ray and neutron scattering, electron microscopy and atom force microscopy (AFM) has to be used to elucidate film morphology and the underlying molecular structure. Here, the thin films were investigated using AFM, optical microscopy and polarized absorption spectroscopy. It was shown that by using numerical method for treating the polarized absorption spectroscopy data, the molecular structure can be elucidated. Further, it was shown that polarized optical spectroscopy is a general tool that allows determination of the molecular order in thin films. Finally, it was found that full control of thermal history and rigorous control of the ionic self-assembly conditions are required to reproducibly make these materials of high nanoscopic order. Similarly, the conditions for spin-casting are shown to be determining for the overall thin film morphology, while molecular order is maintained

Temporal changes in key maternal and fetal factors affecting birth outcomes: A 32-year population-based study in an industrial city

<p>Abstract</p> <p>Background</p> <p>The link between maternal factors and birth outcomes is well established. Substantial changes in society and medical care over time have influenced women's reproductive choices and health, subsequently affecting birth outcomes. The objective of this study was to describe temporal changes in key maternal and fetal factors affecting birth outcomes in Newcastle upon Tyne over three decades, 1961–1992.</p> <p>Methods</p> <p>For these descriptive analyses we used data from a population-based birth record database constructed for the historical cohort <b>Pa</b>rticulate <b>M</b>atter and <b>P</b>erinatal <b>E</b>vents <b>R</b>esearch (PAMPER) study. The PAMPER database was created using details from paper-based hospital delivery and neonatal records for all births during 1961–1992 to mothers resident in Newcastle (out of a total of 109,086 singleton births, 97,809 hospital births with relevant information). In addition to hospital records, we used other sources for data collection on births not included in the delivery and neonatal records, for death and stillbirth registrations and for validation.</p> <p>Results</p> <p>The average family size decreased mainly due to a decline in the proportion of families with 3 or more children. The distribution of mean maternal ages in all and in primiparous women was lowest in the mid 1970s, corresponding to a peak in the proportion of teenage mothers. The proportion of older mothers declined until the late 1970s (from 16.5% to 3.4%) followed by a steady increase. Mean birthweight in all and term babies gradually increased from the mid 1970s. The increase in the percentage of preterm birth paralleled a two-fold increase in the percentage of caesarean section among preterm births during the last two decades. The gap between the most affluent and the most deprived groups of the population widened over the three decades.</p> <p>Conclusion</p> <p>Key maternal and fetal factors affecting birth outcomes, such as maternal age, parity, socioeconomic status, birthweight and gestational age, changed substantially during the 32-year period, from 1961 to 1992. The availability of accurate gestational age is extremely important for correct interpretation of trends in birthweight.</p

COLEC10 is mutated in 3MC patients and regulates early craniofacial development

3MC syndrome is an autosomal recessive heterogeneous disorder with features linked to developmental abnormalities. The main features include facial dysmorphism, craniosynostosis and cleft lip/palate; skeletal structures derived from cranial neural crest cells (cNCC). We previously reported that lectin complement pathway genes COLEC11 and MASP1/3 are mutated in 3MC syndrome patients. Here we define a new gene, COLEC10, also mutated in 3MC families and present novel mutations in COLEC11 and MASP1/3 genes in a further five families. The protein products of COLEC11 and COLEC10, CL-K1 and CL-L1 respectively, form heteromeric complexes. We show COLEC10 is expressed in the base membrane of the palate during murine embryo development. We demonstrate how mutations in COLEC10 (c.25C>T; p.Arg9Ter, c.226delA; p.Gly77Glufs*66 and c.528C>G p.Cys176Trp) impair the expression and/or secretion of CL-L1 highlighting their pathogenicity. Together, these findings provide further evidence linking the lectin complement pathway and complement factors COLEC11 and COLEC10 to morphogenesis of craniofacial structures and 3MC etiology.New life Fundation for Disabled Childre

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery