Induction of labor with Foley catheter and risk of subsequent preterm birth : follow‐up study of two randomized controlled trials (PROBAAT‐1 and ‐2)

Acknowledgements We thank all the women who participated in the PROBAAT trials and all participating institutions and their staff for their contribution to this follow-up study. Funding The original PROBAAT-2 trial was funded by FondsNutsOhra. For the PROBAAT-1 trial and this follow-up study, no funding was received. MV received a doctoral grant for teachers by the Netherlands Organisation for Scientific Research (023.011.051). BM is supported by a NHMRC Practitioner Fellowship (GNT1082548). Funding sources had no role in design, execution, analyses, interpretation, or decision to submit results.Peer reviewedPublisher PD

The randomised uterine septum transsection trial (TRUST) : Design and protocol

Peer reviewedPublisher PD

Methods of induction of labor in women with obesity: A secondary analysis of two multicenter randomized controlled trials

Introduction: Obesity is an increasing public health concern worldwide and can lead to more complications in pregnancy and childbirth. Women with obesity more often require induction of labor for various indications. The aim of this study is to assess which method of induction of labor is safest and most effective in women with obesity. Material and methods: This is a secondary analysis of two randomized controlled trials about induction of labor. Women with a term singleton pregnancy in cephalic presentation, an unfavorable cervix, intact membranes and without a previous cesarean section were randomly allocated to cervical priming with a Foley catheter or vaginal prostaglandin-E2-gel (PROBAAT-I) or a Foley catheter or oral misoprostol (PROBAAT-II). The inclusion and exclusion criteria for the studies were identical. Induction methods were compared in women with obesity (body mass index ≥30.0). Main outcomes were cesarean section and postpartum hemorrhage (blood loss >1000 mL). Results: A total of 2664 women, were included in the trials, 517 of whom were obese: 254 women with obesity received a Foley catheter, 176 oral misoprostol and 87 prostaglandin E2 (PGE2). A cesarean section was performed in 29.1% of women allocated to Foley vs 22.2% in the misoprostol and 23.0% in the PGE2 groups. Comparisons between groups revealed no statistically significant differences: the relative risk [RR] was 1.31 (95% confidence interval [CI] 0.94–1.84) in the Foley vs misoprostol group and 1.27 (95% CI 0.83–1.95) in the Foley vs PGE2 group. The rates of postpartum hemorrhage were comparable (10.6%, 11.4% and 6.9%, respectively; P = 0.512). In women with obesity, more often a switch to another method occurred in the Foley group, (20.1% vs 6.3% in misoprostol vs 1.1% in the PGE2 group; P < 0.001). The risk of a failed Foley placement was higher in women with obesity than in women without obesity (8.3% vs 3.2%; adjusted odds ratio 3.12, 95% CI 1.65–5.90). Conclusions: In women with obesity we found a nonsignificant trend towards an increased rate of cesarean sections in the group induced with a Foley catheter compared to oral misoprostol; however, the study lacked power for this subgroup analysis. The finding of a higher risk of failed placement of a Foley catheter in women with obesity can be used in shared decision making

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Endometrial scratching in women with one failed IVF/ICSI cycle-outcomes of a randomised controlled trial (SCRaTCH)

STUDY QUESTION: Does endometrial scratching in women with one failed IVF/ICSI treatment affect the chance of a live birth of the subsequent fresh IVF/ICSI cycle? SUMMARY ANSWER: In this study, 4.6% more live births were observed in the scratch group, with a likely certainty range between -0.7% and +9.9%. WHAT IS KNOWN ALREADY: Since the first suggestion that endometrial scratching might improve embryo implantation during IVF/ICSI, many clinical trials have been conducted. However, due to limitations in sample size and study quality, it remains unclear whether endometrial scratching improves IVF/ICSI outcomes. STUDY DESIGN, SIZE, DURATION: The SCRaTCH trial was a non-blinded randomised controlled trial in women with one unsuccessful IVF/ICSI cycle and assessed whether a single endometrial scratch using an endometrial biopsy catheter would lead to a higher live birth rate after the subsequent IVF/ICSI treatment compared to no scratch. The study took place in 8 academic and 24 general hospitals. Participants were randomised between January 2016 and July 2018 by a web-based randomisation programme. Secondary outcomes included cumulative 12-month ongoing pregnancy leading to live birth rate. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with one previous failed IVF/ICSI treatment and planning a second fresh IVF/ICSI treatment were eligible. In total, 933 participants out of 1065 eligibles were included (participation rate 88%). MAIN RESULTS AND THE ROLE OF CHANCE: After the fresh transfer, 4.6% more live births were observed in the scratch compared to control group (110/465 versus 88/461, respectively, risk ratio (RR) 1.24 [95% CI 0.96-1.59]). These data are consistent with a true difference of between -0.7% and +9.9% (95% CI), indicating that while the largest proportion of the 95% CI is positive, scratchin

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

The influence of various induction methods on adverse outcomes in small for gestational age neonates : A secondary analysis of the PROBAAT 1 and 2 trials

Funding Information: The original PROBAAT-2 trial was funded by FondsNutsOhra. For the PROBAAT-1 trial and this follow-up study, no funding was received. MV received a doctoral grant for teachers by the Netherlands Organisation for Scientific Research (023.011.051). BM is supported by a NHMRC Practitioner Fellowship (GNT1082548). Funding sources had no role in design, execution, analyses, interpretation, or decision to submit results.Peer reviewedPublisher PD

Cost-effectiveness of salpingotomy and salpingectomy in women with tubal pregnancy (a randomized controlled trial)

STUDY QUESTION: Is salpingotomy cost effective compared with salpingectomy in women with tubal pregnancy and a healthy contralateral tube? SUMMARY ANSWER: Salpingotomy is not cost effective over salpingectomy as a surgical procedure for tubal pregnancy, as its costs are higher without a better ongoing pregnancy rate while risks of persistent trophoblast are higher. WHAT IS KNOWN ALREADY: Women with a tubal pregnancy treated by salpingotomy or salpingectomy in the presence of a healthy contralateral tube have comparable ongoing pregnancy rates by natural conception. Salpingotomy bears the risk of persistent trophoblast necessitating additional medical or surgical treatment. Repeat ectopic pregnancy occurs slightly more often after salpingotomy compared with salpingectomy. Both consequences imply potentially higher costs after salpingotomy. STUDY DESIGN, SIZE, DURATION: We performed an economic evaluation of salpingotomy compared with salpingectomy in an international multicentre randomized controlled trial in women with a tubal pregnancy and a healthy contralateral tube. Between 24 September 2004 and 29 November 2011, women were allocated to salpingotomy (n = 215) or salpingectomy (n = 231). Fertility follow-up was done up to 36 months post-operatively. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: We performed a cost-effectiveness analysis from a hospital perspective. We compared the direct medical costs of salpingotomy and salpingectomy until an ongoing pregnancy occurred by natural conception within a time horizon of 36 months. Direct medical costs included the surgical treatment of the initial tubal pregnancy, readmissions including reinterventions, treatment for persistent trophoblast and interventions for repeat ectopic pregnancy. The analysis was performed according to the intention-to-treat principle. MAIN RESULTS AND THE ROLE OF CHANCE: Mean direct medical costs per woman in the salpingotomy group and in the salpingectomy group were €3319 versus €2958, respectively, with a mean difference of €361 (95% confidence interval €217 to €515). Salpingotomy resulted in a marginally higher ongoing pregnancy rate by natural conception compared with salpingectomy leading to an incremental cost-effectiveness ratio €40 982 (95% confidence interval -€130 319 to €145 491) per ongoing pregnancy. Since salpingotomy resulted in more additional treatments for persistent trophoblast and interventions for repeat ectopic pregnancy, the incremental cost-effectiveness ratio was not informative. LIMITATIONS, REASONS FOR CAUTION: Costs of any subsequent IVF cycles were not included in this analysis. The analysis was limited to the perspective of the hospital. WIDER IMPLICATIONS OF THE FINDINGS: However, a small treatment benefit of salpingotomy might be enough to cover the costs of subsequent IVF. This uncertainty should be incorporated in shared decision-making. Whether salpingotomy should be offered depends on society's willingness to pay for an additional child. STUDY FUNDING/COMPETING INTERESTS: Netherlands Organisation for Health Research and Development, Region Västra Götaland Health & Medical Care Committee. TRIAL REGISTRATION NUMBER: ISRCTN37002267