Which method is best for the induction of labour?: A systematic review, network meta-analysis and cost-effectiveness analysis

Background: More than 150,000 pregnant women in England and Wales have their labour induced each year. Multiple pharmacological, mechanical and complementary methods are available to induce labour. Objective: To assess the relative effectiveness, safety and cost-effectiveness of labour induction methods and, data permitting, effects in different clinical subgroups. Methods: We carried out a systematic review using Cochrane methods. The Cochrane Pregnancy and Childbirth Group’s Trials Register was searched (March 2014). This contains over 22,000 reports of controlled trials (published from 1923 onwards) retrieved from weekly searches of OVID MEDLINE (1966 to current); Cochrane Central Register of Controlled Trials (The Cochrane Library); EMBASE (1982 to current); Cumulative Index to Nursing and Allied Health Literature (1984 to current); ClinicalTrials.gov; the World Health Organization International Clinical Trials Registry Portal; and hand-searching of relevant conference proceedings and journals. We included randomised controlled trials examining interventions to induce labour compared with placebo, no treatment or other interventions in women eligible for third-trimester induction. We included outcomes relating to efficacy, safety and acceptability to women. In addition, for the economic analysis we searched the Database of Abstracts of Reviews of Effects, and Economic Evaluations Databases, NHS Economic Evaluation Database and the Health Technology Assessment database. We carried out a network meta-analysis (NMA) using all of the available evidence, both direct and indirect, to produce estimates of the relative effects of each treatment compared with others in a network. We developed a de novo decision tree model to estimate the cost-effectiveness of various methods. The costs included were the intervention and other hospital costs incurred (price year 2012–13). We reviewed the literature to identify preference-based utilities for the health-related outcomes in the model. We calculated incremental cost-effectiveness ratios, expected costs, utilities and net benefit. We represent uncertainty in the optimal intervention using cost-effectiveness acceptability curves. Results: We identified 1190 studies; 611 were eligible for inclusion. The interventions most likely to achieve vaginal delivery (VD) within 24 hours were intravenous oxytocin with amniotomy [posterior rank 2; 95% credible intervals (CrIs) 1 to 9] and higher-dose (≥ 50 μg) vaginal misoprostol (rank 3; 95% CrI 1 to 6). Compared with placebo, several treatments reduced the odds of caesarean section, but we observed considerable uncertainty in treatment rankings. For uterine hyperstimulation, double-balloon catheter had the highest probability of being among the best three treatments, whereas vaginal misoprostol (≥ 50 μg) was most likely to increase the odds of excessive uterine activity. For other safety outcomes there were insufficient data or there was too much uncertainty to identify which treatments performed ‘best’. Few studies collected information on women’s views. Owing to incomplete reporting of the VD within 24 hours outcome, the cost-effectiveness analysis could compare only 20 interventions. The analysis suggested that most interventions have similar utility and differ mainly in cost. With a caveat of considerable uncertainty, titrated (low-dose) misoprostol solution and buccal/sublingual misoprostol had the highest likelihood of being cost-effective. Limitations: There was considerable uncertainty in findings and there were insufficient data for some planned subgroup analyses. Conclusions: Overall, misoprostol and oxytocin with amniotomy (for women with favourable cervix) is more successful than other agents in achieving VD within 24 hours. The ranking according to safety of different methods was less clear. The cost-effectiveness analysis suggested that titrated (low-dose) oral misoprostol solution resulted in the highest utility, whereas buccal/sublingual misoprostol had the lowest cost. There was a high degree of uncertainty as to the most cost-effective intervention

Tax Planning vs. the Optimal Capitalization Rate

This thesis deals with the legislative problem of thin and thick capitalization of subsidiary companies situated abroad. This kind of companies are often used for tax planning purposes, as means for transferring company profit from a high tax state to a low tax state. Today, the legislative flora around the world mainly focuses on the question"how low/high can the capitalization level of the company be, before thin/thick capitalization can be considered to be at hand?". Instead, this thesis raises the question"how far from the optimal capitalization rate is a probable capitalization level for a company, and can this be an alternative approach to legislation?". The object of the thesis is to point out possibilities, as well as obstacles, to this approach, but also to show a possible design of a regulation based on the approach. It is discussed whether the uncertainty in determining the optimal capitalization rate overthrows the theory behind the approach, or in fact strengthens it. Several advantages, but also a number of drawbacks, are shown. Hence, the conclusion of the study is neither in favor of, nor against, a regulation founded on the optimal capitalization rate, but rather an invitation to further discussion and calculations

Effects of oophorectomy, sympathetic denervation and sex steroids on uterine norepinephrine content and myometrial contractile response to norepinephrine in the guinea pig

Studies were performed in guinea pigs to elucidate alterations in endogenous uterine norepinephrine (NE) levels and changes in the contractile response to exogenous NE following local sympathetic denervation, oophorectomy, or treatment with sex steroids. Both in intact and oophorectomized animals the myometrial NE concentration was reduced after sex steroid treatment (0.5 microgram 17-beta-estradiol, or 0.1 microgram estradiol plus 2 mg progesterone, during 2 weeks), mainly as a result of increased uterine weight. After surgical removal of the hypogastric nerves and section of the suspensory ligaments, a similar response to sex steroids was seen if the animals had previously been oophorectomized. The myometrial contractile activity induced by exogenous NE was measured in vitro. The EC50 values (NE concentration giving 50% of the maximal response) showed a similar pattern of variations after hormonal treatment and oophorectomy as did the concentration of endogenous NE. Thus, exposure to the steroids leading to a reduction of neuronal NE also caused an increased sensitivity of the myometrial smooth musculature to exogenous NE, and in the various experimental groups the two parameters showed a close and significant relationship. The underlying mechanism may induce a denervation supersensitivity to NE induced by exposure to estrogen and progesterone

Modified Ritgen's maneuver for anal sphincter injury at delivery: a randomized controlled trial.

OBJECTIVE: To investigate whether Ritgen's maneuver decreases the risk of third- to fourth-degree perineal tears compared with simple perineal support. METHODS: A total of 1,623 nulliparous women in term labor, singleton pregnancy, and cephalic presentation were randomly assigned to Ritgen's maneuver or standard care. Ritgen's maneuver denotes extracting the fetal head, using one hand to pull the fetal chin from between the maternal anus and the coccyx, and the other on the fetal occiput to control speed of delivery. Ritgen's maneuver was performed during a uterine contraction, rather than, as originally recommended, between contractions. Our standard care entailed perineal support with one hand and control of the speed of crowning with the other, and use of Ritgen's maneuver only on specific indications. Women delivered by cesarean delivery (n=10) or instrumentally (n=142) were excluded, as well as 39 erroneously included women (parous or in preterm labor), six inaccurately assigned participants, one with missing data, and two participants who withdrew consent. For the remaining 1,423 women, the result was analyzed according to intention to treat. RESULTS: Ritgen's maneuver was performed in 554 (79.6%) of 696 women randomly assigned to this procedure and in 31 (4.3%) of 727 women randomly assigned to simple perineal support. The rate of third- to fourth-degree tears was 5.5% (n=38) in women assigned to Ritgen's maneuver and 4.4% (n=32) in those assigned to simple perineal support (relative risk 1.24; 95% confidence interval 0.78-1.96). CONCLUSION: Ritgen's maneuver does not decrease the risk of anal sphincter injury at delivery, at least not when performed during a contraction