Predicting cesarean section and uterine rupture among women attempting vaginal birth after prior cesarean section

<p><b>Background:</b> There is currently no validated method for antepartum prediction of the risk of failed vaginal birth after cesarean section and no information on the relationship between the risk of emergency cesarean delivery and the risk of uterine rupture.</p> <p><b>Methods and Findings:</b> We linked a national maternity hospital discharge database and a national registry of perinatal deaths. We studied 23,286 women with one prior cesarean delivery who attempted vaginal birth at or after 40-wk gestation. The population was randomly split into model development and validation groups. The factors associated with emergency cesarean section were maternal age (adjusted odds ratio [OR] = 1.22 per 5-y increase, 95% confidence interval [CI]: 1.16 to 1.28), maternal height (adjusted OR = 0.75 per 5-cm increase, 95% CI: 0.73 to 0.78), male fetus (adjusted OR = 1.18, 95% CI: 1.08 to 1.29), no previous vaginal birth (adjusted OR = 5.08, 95% CI: 4.52 to 5.72), prostaglandin induction of labor (adjusted OR = 1.42, 95% CI: 1.26 to 1.60), and birth at 41-wk (adjusted OR = 1.30, 95% CI: 1.18 to 1.42) or 42-wk (adjusted OR = 1.38, 95% CI: 1.17 to 1.62) gestation compared with 40-wk. In the validation group, 36% of the women had a low predicted risk of caesarean section (<20%) and 16.5% of women had a high predicted risk (>40%); 10.9% and 47.7% of these women, respectively, actually had deliveries by caesarean section. The predicted risk of caesarean section was also associated with the risk of all uterine rupture (OR for a 5% increase in predicted risk = 1.22, 95% CI: 1.14 to 1.31) and uterine rupture associated with perinatal death (OR for a 5% increase in predicted risk = 1.32, 95% CI: 1.02 to 1.73). The observed incidence of uterine rupture was 2.0 per 1,000 among women at low risk of cesarean section and 9.1 per 1,000 among those at high risk (relative risk = 4.5, 95% CI: 2.6 to 8.1). We present the model in a simple-to-use format.</p> <p><b>Conclusions:</b> We present, to our knowledge, the first validated model for antepartum prediction of the risk of failed vaginal birth after prior cesarean section. Women at increased risk of emergency caesarean section are also at increased risk of uterine rupture, including catastrophic rupture leading to perinatal death.</p&gt

Multiple imputation of multiple multi-item scales when a full imputation model is infeasible.

BACKGROUND: Missing data in a large scale survey presents major challenges. We focus on performing multiple imputation by chained equations when data contain multiple incomplete multi-item scales. Recent authors have proposed imputing such data at the level of the individual item, but this can lead to infeasibly large imputation models. METHODS: We use data gathered from a large multinational survey, where analysis uses separate logistic regression models in each of nine country-specific data sets. In these data, applying multiple imputation by chained equations to the individual scale items is computationally infeasible. We propose an adaptation of multiple imputation by chained equations which imputes the individual scale items but reduces the number of variables in the imputation models by replacing most scale items with scale summary scores. We evaluate the feasibility of the proposed approach and compare it with a complete case analysis. We perform a simulation study to compare the proposed method with alternative approaches: we do this in a simplified setting to allow comparison with the full imputation model. RESULTS: For the case study, the proposed approach reduces the size of the prediction models from 134 predictors to a maximum of 72 and makes multiple imputation by chained equations computationally feasible. Distributions of imputed data are seen to be consistent with observed data. Results from the regression analysis with multiple imputation are similar to, but more precise than, results for complete case analysis; for the same regression models a 39% reduction in the standard error is observed. The simulation shows that our proposed method can perform comparably against the alternatives. CONCLUSIONS: By substantially reducing imputation model sizes, our adaptation makes multiple imputation feasible for large scale survey data with multiple multi-item scales. For the data considered, analysis of the multiply imputed data shows greater power and efficiency than complete case analysis. The adaptation of multiple imputation makes better use of available data and can yield substantively different results from simpler techniques

Derivation and assessment of risk prediction models using case-cohort data

Background Case-cohort studies are increasingly used to quantify the association of novel factors with disease risk. Conventional measures of predictive ability need modification for this design. We show how Harrell’s C-index, Royston’s D, and the category-based and continuous versions of the net reclassification index (NRI) can be adapted. Methods We simulated full cohort and case-cohort data, with sampling fractions ranging from 1% to 90%, using covariates from a cohort study of coronary heart disease, and two incidence rates. We then compared the accuracy and precision of the proposed risk prediction metrics. Results The C-index and D must be weighted in order to obtain unbiased results. The NRI does not need modification, provided that the relevant non-subcohort cases are excluded from the calculation. The empirical standard errors across simulations were consistent with analytical standard errors for the C-index and D but not for the NRI. Good relative efficiency of the prediction metrics was observed in our examples, provided the sampling fraction was above 40% for the C-index, 60% for D, or 30% for the NRI. Stata code is made available. Conclusions Case-cohort designs can be used to provide unbiased estimates of the C-index, D measure and NRI

How is overall survival assessed in randomised clinical trials in cancer and are subsequent treatment lines considered? A systematic review

Background Overall survival is the “gold standard” endpoint in cancer clinical trials. It plays a key role in determining the clinical- and cost-effectiveness of a new intervention and whether it is recommended for use in standard of care. The assessment of overall survival usually requires trial participants to be followed up for a long period of time. In this time, they may stop receiving the trial intervention and receive subsequent anti-cancer treatments, which also aim to extend survival, during trial follow-up. This can potentially change the interpretation of overall survival in the context of the clinical trial. This review aimed to determine how overall survival has been assessed in cancer clinical trials and whether subsequent anti-cancer treatments are considered. Methods Two searches were conducted using MEDLINE within OVID© on the 9th of November 2021. The first sought to identify papers publishing overall survival results from randomised controlled trials in eight reputable journals and the second to identify papers mentioning or considering subsequent treatments. Papers published since 2010 were included if presenting or discussing overall survival in the context of treating cancer. Results One hundred and thirty-four papers were included. The majority of these were presenting clinical trial results (98, 73%). Of these, 45 (46%) reported overall survival as a (co-) primary endpoint. A lower proportion of papers including overall survival as a (co-) primary endpoint compared to a secondary endpoint were published in recent years. The primary analysis of overall survival varied across the papers. Fifty-nine (60%) mentioned subsequent treatments. Seven papers performed additional analysis, primarily when patients in the control arm received the experimental treatment during trial follow-up (treatment switching). Discussion Overall survival has steadily moved from being the primary to a secondary endpoint. However, it is still of interest with papers presenting overall survival results with the caveat of subsequent treatments, but little or no investigation into their effect. This review shows that there is a methodological gap for what researchers should do when trial participants receive anti-cancer treatment during trial follow-up. Future research will identify the stakeholder opinions, on how this methodological gap should be addressed

On the multiplicity of the O-star Cyg OB2 #8A and its contribution to the gamma-ray source 3EG J2033+4118

We present the results of an intensive spectroscopic campaign in the optical waveband revealing that Cyg OB2 #8A is an O6 + O5.5 binary system with a period of about 21.9 d. Cyg OB2 #8A is a bright X-ray source, as well as a non-thermal radio emitter. We discuss the binarity of this star in the framework of a campaign devoted to the study of non-thermal emitters, from the radio waveband to gamma-rays. In this context, we attribute the non-thermal radio emission from this star to a population of relativistic electrons, accelerated by the shock of the wind-wind collision. These relativistic electrons could also be responsible for a putative gamma-ray emission through inverse Compton scattering of photospheric UV photons, thus contributing to the yet unidentified EGRET source 3EG J2033+4118.Comment: 8 pages, 4 figures, conference on "The Multiwavelength Approach to Gamma-Ray Sources", to appear in Ap&S

Collective effects of stellar winds and unidentified gamma-ray sources

We study collective wind configurations produced by a number of massive stars, and obtain densities and expansion velocities of the stellar wind gas that is to be target, in this model, of hadronic interactions. We study the expected $\gamma$-ray emission from these regions, considering in an approximate way the effect of cosmic ray modulation. We compute secondary particle production (electrons from knock-on interactions and electrons and positrons from charged pion decay), and solve the loss equation with ionization, synchrotron, bremsstrahlung, inverse Compton, and expansion losses. We provide examples where configurations can produce sources for GLAST satellite, and the MAGIC, HESS, or VERITAS telescopes in non-uniform ways, i.e., with or without the corresponding counterparts. We show that in all cases we studied no EGRET source is expected

A genome-wide screen for variants influencing certolizumab pegol response in a moderate to severe rheumatoid arthritis population

Certolizumab pegol (CZP) is a PEGylated Fc-free tumor necrosis factor (TNF) inhibitor antibody approved for use in the treatment of rheumatoid arthritis (RA), Crohn's disease, psoriatic arthritis, axial spondyloarthritis and psoriasis. In a clinical trial of patients with severe RA, CZP improved disease symptoms in approximately half of patients. However, variability in CZP efficacy remains a problem for clinicians, thus, the aim of this study was to identify genetic variants predictive of CZP response. We performed a genome-wide association study (GWAS) of 302 RA patients treated with CZP in the REALISTIC trial to identify common single nucleotide polymorphisms (SNPs) associated with treatment response. Wholeexome sequencing was also performed for 74 CZP extreme responders and non-responders within the same population, as well as 1546 population controls. No common SNPs or rare functional variants were significantly associated with CZP response, though a non-significant enrichment in the RA-implicated KCNK5 gene was observed. Two SNPs near spondin- 1 and semaphorin-4G approached genome-wide significance. The results of the current study did not provide an unambiguous predictor of CZP response

Gamma rays from colliding winds of massive stars

Colliding winds of massive binaries have long been considered as potential sites of non-thermal high-energy photon production. This is motivated by the detection of non-thermal spectra in the radio band, as well as by correlation studies of yet unidentified EGRET gamma-ray sources with source populations appearing in star formation regions. This work re-considers the basic radiative processes and its properties that lead to high energy photon production in long-period massive star systems. We show that Klein-Nishina effects as well as the anisotropic nature of the inverse Compton scattering, the dominating leptonic emission process, likely yield spectral and variability signatures in the gamma-ray domain at or above the sensitivity of current or upcoming gamma ray instruments like GLAST-LAT. In addition to all relevant radiative losses, we include propagation (such as convection in the stellar wind) as well as photon absorption effects, which a priori can not be neglected. The calculations are applied to WR140 and WR147, and predictions for their detectability in the gamma-ray regime are provided. Physically similar specimen of their kind like WR146, WR137, WR138, WR112 and WR125 may be regarded as candidate sources at GeV energies for near-future gamma-ray experiments. Finally, we discuss several aspects relevant for eventually identifying this source class as a gamma-ray emitting population. Thereby we utilize our findings on the expected radiative behavior of typical colliding wind binaries in the gamma-ray regime as well as its expected spatial distribution on the gamma-ray sky

Effect of atrial fibrillation on endovascular thrombectomy for acute ischemic stroke. A meta-analysis of individual patient data from six randomised trials: Results from the HERMES collaboration

Background: Atrial fibrillation is an important risk factor for ischemic stroke, and is associated with an increased risk of poor outcome after ischemic stroke. Endovascular thrombectomy is safe and effective in acute ischemic stroke patients with large vessel occlusion of the anterior circulation. This meta-analysis aims to investigate whether there is an interaction between atrial fibrillation and treatment effect of endovascular thrombectomy, and secondarily whether atrial fibrillation is associated with worse outcome in patients with ischemic stroke due to large vessel occlusion. Methods: Individual patient data were from six of the recent randomised clinical trials (MR CLEAN, EXTEND-IA, REVASCAT, SWIFT PRIME, ESCAPE, PISTE) in which endovascular thrombectomy plus standard care was compared to standard care alone. Primary outcome measure was the shift on the modified Rankin scale (mRS) at 90 days. Secondary outcomes were functional independence (mRS 0–2) at 90 days, National Institutes of Health Stroke Scale score at 24 h, symptomatic intracranial hemorrhage and mortality at 90 days. The primary effect parameter was the adjusted common odds ratio, estimated with ordinal logistic regression (shift analysis); treatment effect modification of atrial fibrillation was assessed with a multiplicative interaction term. Results: Among 1351 patients, 447 p

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results