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Background: This study aims to determine the prognostic accuracy of term MRI in very preterm born (≤32 weeks) or low-birth-weight (≤1500 g) infants for long-term (>18 months) developmental outcomes., Methods: We performed a systematic review searching Central, Medline, Embase, and PsycInfo. Two independent reviewers performed study selection, data extraction, and quality assessment. We documented sensitivity and specificity for three different MRI findings (white matter abnormalities (WMA), brain abnormality (BA), and diffuse excessive high signal intensity (DEHSI)), related to developmental outcomes including cerebral palsy (CP), visual and/or hearing problems, motor, neurocognitive, and behavioral function. Using bivariate meta-analysis, we estimated pooled sensitivity and specificity and plotted summary receiver operating characteristic (sROC) curves for different cut-offs of MRI., Results: We included 20 papers published between 2000 and 2013. Quality of included studies varied. Pooled sensitivity and specificity values (95 % confidence interval (CI)) for prediction of CP combining the three different MRI findings (using normal/mild vs. moderate/severe cut-off) were 77 % (53 to 91 %) and 79 % (51 to 93 %), respectively. For prediction of motor function, the values were 72 % (52 to 86 %) and 62 % (29 to 87 %), respectively. Prognostic accuracy for visual and/or hearing problems, neurocognitive, and/or behavioral function was poor. sROC curves of the individual MRI findings showed that presence of WMA provided the best prognostic accuracy whereas DEHSI did not show any potential prognostic accuracy., Conclusions: This study shows that presence of moderate/severe WMA on MRI around term equivalent age can predict CP and motor function in very preterm or low-birth-weight infants with moderate sensitivity and specificity. Its ability to predict other long-term outcomes such as neurocognitive and behavioral impairments is limited. Also, other white matter related tests as BA and DEHSI demonstrated limited prognostic value., Systematic Review Registration: PROSPERO CRD42013006362.

Background: Children and their parents are at risk of posttraumatic stress disorder (PTSD) following injury due to pediatric accidental trauma. Screening could help predict those at greatest risk and provide an opportunity for monitoring so that early intervention may be provided. The purpose of this study was to evaluate the Screening Tool for Early Predictors of Posttraumatic Stress Disorder (STEPP) in a mixed-trauma sample in a non-English speaking country (the Netherlands)., Methods: Children aged 8-18 and one of their parents were recruited in two academic level I trauma centers. The STEPP was assessed in 161 children (mean age 13.9 years) and 156 parents within one week of the accident. Three months later, clinical diagnoses and symptoms of PTSD were assessed in 147 children and 135 parents. We used the Anxiety Disorders Interview Schedule for DSM-IV - Child and Parent version, the Children's Revised Impact of Event Scale and the Impact of Event Scale-Revised. Receiver Operating Characteristic analyses were performed to estimate the Areas Under the Curve as a measure of performance and to determine the optimal cut-off score in our sample. Sensitivity, specificity, positive and negative predictive values were calculated. The aim was to maximize both sensitivity and negative predictive values., Results: PTSD was diagnosed in 12% of the children; 10% of their parents scored above the cut-off point for PTSD. At the originally recommended cut-off scores (4 for children, 3 for parents), the sensitivity in our sample was 41% for children and 54% for parents. Negative predictive values were 92% for both groups. Adjusting the cut-off scores to 2 improved sensitivity to 82% for children and 92% for parents, with negative predictive values of 92% and 96%, respectively., Conclusions: With adjusted cut-off scores, the STEPP performed well: 82% of the children and 92% of the parents with a subsequent positive diagnosis were identified correctly. Special attention in the screening procedure is required because of a high rate of false positives. The STEPP appears to be a valid and useful instrument that can be used in the Netherlands as a first screening method in stepped psychotrauma care following accidents.

Objective: To determine the effectiveness of a client or care-provider strategy to improve the implementation of external cephalic version., Design: Cluster randomized controlled trial., Setting: Twenty-five clusters; hospitals and their referring midwifery practices randomly selected in the Netherlands., Population: Singleton breech presentation from 32 weeks of gestation onwards., Methods: We randomized clusters to a client strategy (written information leaflets and decision aid), a care-provider strategy (1-day counseling course focused on knowledge and counseling skills), a combined client and care-provider strategy and care-as-usual strategy. We performed an intention-to-treat analysis., Main Outcome Measures: Rate of external cephalic version in various strategies. Secondary outcomes were the percentage of women counseled and opting for a version attempt., Results: The overall implementation rate of external cephalic version was 72% (1169 of 1613 eligible clients) with a range between clusters of 8-95%. Neither the client strategy (OR 0.8, 95% CI 0.4-1.5) nor the care-provider strategy (OR 1.2, 95% CI 0.6-2.3) showed significant improvements. Results were comparable when we limited the analysis to those women who were actually offered intervention (OR 0.6, 95% CI 0.3-1.4 and OR 2.0, 95% CI 0.7-4.5)., Conclusions: Neither a client nor a care-provider strategy improved the external cephalic version implementation rate for breech presentation, neither with regard to the number of version attempts offered nor the number of women accepting the procedure., (© 2015 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: To evaluate whether tocolysis with nifedipine can be omitted in women with symptoms of preterm labor, a shortened cervix, and negative fetal fibronectin test., Study Design: A randomized noninferiority trial was performed in all Dutch perinatal centers. Women with symptoms of preterm labor between 24 and 34 weeks, intact membranes, cervical length between 10 and 30 mm, and negative fibronectin test were randomly allocated to nifedipine (80 mg/day) or placebo. The primary outcome was delivery within 7 days. Secondary outcomes were severe neonatal morbidity and mortality. We also followed all eligible nonrandomized women., Results: We allocated 37 women to nifedipine and 36 women to placebo. In the nifedipine group, three women (8.1%) delivered within 7 days, compared with one woman (2.8%) in the placebo group (difference -5.3%; one-sided 95% confidence limit 4.5%). Median gestational age at delivery were respectively 37 + 0 (interquartile range [IQR] 34 + 6 to 38 + 5) and 38 + 2 (IQR 37 + 0 to 39 + 6) weeks (p = 0.008). In the nifedipine group, three pregnancies (8.1%) had a poor outcome; there were no poor outcomes in the placebo group. We observed similar trends in eligible nonrandomized women., Conclusion: In symptomatic women with preterm labor, a shortened cervix, and negative fibronectin test, placebo treatment is not inferior to tocolysis with nifedipine., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Recently we developed and validated generic quality indicators that define 'appropriate antibiotic use' in hospitalized adults treated for a (suspected) bacterial infection. Previous studies have shown that with appropriate antibiotic use a reduction of 13% of length of hospital stay can be achieved. Our main objective in this project is to provide hospitals with an antibiotic checklist based on these quality indicators, and to evaluate the introduction of this checklist in terms of (cost-) effectiveness., Methods/design: The checklist applies to hospitalized adults with a suspected bacterial infection for whom antibiotic therapy is initiated, at first via the intravenous route. A stepped wedge study design will be used, comparing outcomes before and after introduction of the checklist in nine hospitals in the Netherlands. At least 810 patients will be included in both the control and the intervention group. The primary endpoint is length of hospital stay. Secondary endpoints are appropriate antibiotic use measured by the quality indicators, admission to and duration of intensive care unit stay, readmission within 30 days, mortality, total antibiotic use, and costs associated with implementation and hospital stay. Differences in numerical endpoints between the two periods will be evaluated with mixed linear models; for dichotomous outcomes generalized estimating equation models will be used. A process evaluation will be performed to evaluate the professionals' compliance with use of the checklist. The key question for the economic evaluation is whether the benefits of the checklist, which include reduced antibiotic use, reduced length of stay and associated costs, justify the costs associated with implementation activities as well as daily use of the checklist., Discussion: If (cost-) effective, the AB-checklist will provide physicians with a tool to support appropriate antibiotic use in adult hospitalized patients who start with intravenous antibiotics., Trial Registration: Dutch trial registry: NTR4872.

To prevent adverse long-term effects, children who suffer from posttraumatic stress symptoms (PTSS) need treatment. Trauma-focused cognitive behavioral therapy (TF-CBT) is an established treatment for children with PTSS. However, alternatives are important for non-responders or if TF-CBT trained therapists are unavailable. Eye movement desensitization and reprocessing (EMDR) is a promising treatment for which sound comparative evidence is lacking. The current randomized controlled trial investigates the effectiveness and efficiency of both treatments. Forty-eight children (8-18 years) were randomly assigned to eight sessions of TF-CBT or EMDR. The primary outcome was PTSS as measured with the Clinician-Administered PTSD Scale for Children and Adolescents (CAPS-CA). Secondary outcomes included parental report of child PTSD diagnosis status and questionnaires on comorbid problems. The Children's Revised Impact of Event Scale was administered during the course of treatment. TF-CBT and EMDR showed large reductions from pre- to post-treatment on the CAPS-CA (-20.2; 95% CI -12.2 to -28.1 and -20.9; 95% CI -32.7 to -9.1). The difference in reduction was small and not statistically significant (mean difference of 0.69, 95% CI -13.4 to 14.8). Treatment duration was not significantly shorter for EMDR (p = 0.09). Mixed model analysis of monitored PTSS during treatment showed a significant effect for time (p < 0.001) but not for treatment (p = 0.44) or the interaction of time by treatment (p = 0.74). Parents of children treated with TF-CBT reported a significant reduction of comorbid depressive and hyperactive symptoms. TF-CBT and EMDR are effective and efficient in reducing PTSS in children.

Objective: To evaluate whether a model to predict a failed endometrial biopsy in women with postmenopausal bleeding (PMB) and a thickened endometrium can reduce costs without compromising diagnostic accuracy., Design, Setting, and Population: Model based cost-minimization analysis., Methods: A decision analytic model was designed to compare two diagnostic strategies for women with PMB: (I) attempting office endometrial biopsy and performing outpatient hysteroscopy after failed biopsy and (II) predicted probability of a failed endometrial biopsy based on patient characteristics to guide the decision for endometrial biopsy or immediate hysteroscopy. Robustness of assumptions regarding costs was evaluated in sensitivity analyses., Main Outcome Measures: Costs for the different strategies., Results: At different cut-offs for the predicted probability of failure of an endometrial biopsy, strategy I was generally less expensive than strategy II. The costs for strategy I were always € 460; the costs for strategy II varied between € 457 and € 475. At a 65% cut-off, a possible saving of € 3 per woman could be achieved., Conclusions: Individualizing the decision to perform an endometrial biopsy or immediate hysteroscopy in women presenting with postmenopausal bleeding based on patient characteristics does not increase the efficiency of the diagnostic work-up.

Background: External cephalic version (ECV) reduces the rate of elective cesarean sections as a result of breech presentation. Several studies have shown that not all eligible women undergo an ECV attempt. The aim of this study was to evaluate the implementation of ECV in the Netherlands and to explain variation in implementation rates with hospital characteristics and individual factors., Methods: We invited 40 hospitals to participate in this retrospective cohort study. We reviewed hospital charts for all singleton breech deliveries from 36 weeks' gestation and onwards between January 2008 and December 2009. We documented whether an ECV attempt was performed, reasons for not performing an attempt, mode of delivery, and hospital characteristics., Results: We included 4,770 women from 36 hospitals. ECV was performed in 2,443 women (62.2% of eligible women, range 8.2-83.6% in different hospitals). Implementation rates were higher in teaching hospitals, hospitals with special office hours for ECV, larger obstetric units, and hospitals located in larger cities. Suboptimal implementation was mainly caused by health care providers who did not offer ECV., Conclusion: ECV implementation rates vary widely among hospitals. Suboptimal implementation is mostly caused by the care provider not offering the treatment and secondly due to women not opting for the offered attempt. A prerequisite for designing a proper implementation strategy is a detailed understanding of the exact reasons for not offering and not opting for ECV., (© 2014 Wiley Periodicals, Inc.)

Objectives: To assess the cost-effectiveness of post-partum screening on cardiovascular risk factors and subsequent treatment in women with a history of gestational hypertension or pre-eclampsia at term., Study Design: Two separate Markov models evaluated the cost-effectiveness analysis of hypertension (HT) screening and screening on metabolic syndrome (MetS), respectively, as compared to current practice in women with a history of term hypertensive pregnancy disorders. Analyses were performed from the Dutch health care perspective, using a lifetime horizon. One-way sensitivity analyses and Monte Carlo simulation evaluated the robustness of the results., Results: Both screening on HT and MetS in women with a history of gestational hypertension or pre-eclampsia resulted in increase in life expectancy (HT screening 0.23year (95% CI -0.06 to 0.54); MetS screening 0.14years (95% CI -0.16 to 0.45)). The gain in QALYs was limited, with HT screening and MetS screening generating 0.04 QALYs (95% CI -0.12 to 0.20) and 0.03 QALYs (95% CI -0.14 to 0.19), resulting in costs to gain one QALY of €4228 and €28,148, respectively. Analyses for uncertainty showed a chance of 74% and 75%, respectively, that post-partum screening is cost-effective at a threshold of €60,000/QALY., Conclusions: According to the available knowledge post-partum screening on cardiovascular risk factors and subsequent treatment in women with a history of gestational hypertension or pre-eclampsia at term is likely to be cost-effective., (Copyright © 2014 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Objective: To assess the cost-effectiveness of a cervical pessary to prevent preterm delivery in women with a multiple pregnancy., Methods: The study design comprised an economic analysis of data from a randomized clinical trial evaluating cervical pessaries (ProTWIN). Women with a multiple pregnancy were included and an economic evaluation was performed from a societal perspective. Costs were estimated between the time of randomization and 6 weeks postpartum. The prespecified subgroup of women with a cervical length (CL) < 25(th) centile (< 38 mm) was analyzed separately. The primary endpoint was poor perinatal outcome occurring up to 6 weeks postpartum. Direct medical costs and health outcomes were estimated and incremental cost-effectiveness ratios for costs to prevent one poor outcome were calculated., Results: Mean costs in the pessary group (n = 401) were € 21,783 vs € 21,877 in the group in which no pessary was used (n = 407) (difference, -€ 94; 95% CI, -€ 5975 to € 5609). In the prespecified subgroup of women with a CL < 38 mm we demonstrated a significant reduction in poor perinatal outcome (12% vs 29%; RR, 0.40; 95% CI, 0.19-0.83). Mean costs in the pessary group (n = 78) were € 25,141 vs € 30,577 in the no-pessary group (n = 55) (difference, -€ 5436 (95% CI, -€ 11,001 to € 1456). In women with a CL < 38 mm, pessary treatment was the dominant strategy (more effective and less costly) with a probability of 94%., Conclusion: Cervical pessaries in women with a multiple pregnancy involve costs comparable to those in women without pessary treatment. However, in women with a CL < 38 mm, treatment with a cervical pessary appears to be highly cost-effective., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

We evaluated 800 hospitalized patients with a complicated urinary tract infection, from whom both a blood and a urine culture were obtained on the first day of antibiotic treatment. Urine cultures were positive in 70% of patients, and blood cultures were positive in 29%. In 7% of patients, uropathogens caused bacteraemia with a pathogen that was not isolated from urine. Receiving antibiotic therapy at the moment of hospitalization was the only factor independently associated with discordant culture results (OR, 2.06; 95% CI, 1.18-3.61). For those receiving antibiotics at the moment of hospitalization, blood cultures have additional diagnostic value over urine cultures., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)

The Children's Revised Impact of Event Scale (CRIES-13) is a brief self-report measure designed to screen children for posttraumatic stress disorder (PTSD). This study investigates the psychometric properties of a Dutch version of the CRIES-13-parent version and evaluates its correlation with the child version. A sample of 59 trauma-exposed children (8 years-18 years) and their parents completed an assessment including the CRIES-13 (child/parent version) along with the Anxiety Disorders Interview Schedule for DSM-IV: Parent version. Results demonstrated good internal consistency (α = .87) with acceptable values for the 3 subscales. A strong correlation (r = .73) with another measure of PTSD and lower correlations with a behavioral measure (r = .15 to .38) were found, confirming the convergent/divergent validity. A cutoff score ≥ 31 emerged as the best balance between sensitivity and specificity, and correctly classified 83.6% of all children as having a diagnosis of PTSD. This study provides support for the reliability and validity of the CRIES-13-parent version as a screening measure for posttraumatic stress in children., (Copyright © 2014 International Society for Traumatic Stress Studies.)

Background: Thin endometrium on ultrasound in the course of ovarian hyperstimulation has been thought to be associated with poor success rates after IVF, even in the absence of prior intrauterine surgery or infection. To assess the clinical significance of endometrial thickness (EMT) for IVF outcome, we performed a systematic review and meta-analysis., Methods: The electronic databases Pubmed, Cochrane and Embase were searched up to October 2013 for articles that studied the association between EMT and IVF outcome. The articles had to be written in the English or Dutch language. Studies were included if two-by-two tables for EMT and pregnancy rates could be constructed. Study quality was scored using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. Summary receiver operating characteristic (sROC) curves were estimated to assess the accuracy of EMT in the prediction of pregnancy. In addition, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a Mantel-Haenszel random effect model expressing the association between EMT and pregnancy chances. Meta-regression was performed to determine if female age and number of oocytes at retrieval interacted in the estimated effect of EMT on IVF outcome., Results: A total of 1170 studies was retrieved by the search. The overall quality of the 22 studies included in the review and meta-analysis was moderate. The estimated sROC curve indicated a virtually absent discriminatory capacity of EMT in the prediction of pregnancy. A thin endometrium (≤ 7 mm) was observed in only 2.4% of the reported cases (260/10 724). In these cases a trend towards lower ongoing pregnancy and live birth rates for women with EMT ≤ 7 mm was observed [OR 0.38 (95% CI 0.09-1.5)]. The probability of clinical pregnancy for an EMT ≤ 7 mm was significantly lower compared with cases with EMT > 7 mm [23.3% versus 48.1%, OR 0.42 (95% CI 0.27-0.67)]. Positive and negative predictive values for the outcome of clinical pregnancy 77 and 48%, respectively. The relationship between the number of oocytes and female age on the one hand and pregnancy on the other hand was very weak making correction for these variables unfeasible., Conclusions: Current data indicate that EMT has a limited capacity to identify women who have a low chance to conceive after IVF. The frequently reported cut-off of 7 mm is related to a lower chance of pregnancy, but occurs infrequently. The use of EMT as a tool to decide on cycle cancellation, freezing of all embryos or refraining from further IVF treatment seems not to be justified based on the current meta-analysis. Further research is needed to investigate the real independent significance of EMT in IVF., (© The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To estimate the performance of combining cervical length measurement with fetal fibronectin testing in predicting delivery in women with symptoms of preterm labor., Methods: We conducted a prospective nationwide cohort study in all 10 perinatal centers in The Netherlands. Women with symptoms of preterm labor between 24 and 34 weeks of gestation with intact membranes were included. In all women, qualitative fibronectin testing (0.050-microgram/mL cutoff) and cervical length measurement were performed. Logistic regression was used to predict spontaneous preterm delivery within 7 days after testing. A risk less than 5%, corresponding to the risk for women with a cervical length of at least 25 mm, was considered as low risk., Results: Between December 2009 and August 2012, 714 women were enrolled. Fibronectin results and cervical length were available for 665 women, of whom 80 (12%) delivered within 7 days. Women with a cervical length of at least 30 mm or with a cervical length between 15 and 30 mm with a negative fibronectin result were at low risk (less than 5%) of spontaneous delivery within 7 days. Fibronectin testing in case of a cervical length between 15 and 30 mm additionally classified 103 women (15% of the cohort) as low risk and 36 women (5% of the cohort) as high risk., Conclusion: Cervical length measurement, combined with fetal fibronectin testing in case of a cervical length between 15 and 30 mm, improves identification of women with a low risk to deliver spontaneously within 7 days., Level of Evidence: II.

Early identification of posttraumatic stress disorder (PTSD) in children is important to offer them appropriate and timely treatment. The Children's Revised Impact of Event Scale (CRIES) is a brief self-report measure designed to screen children for PTSD. Research regarding the diagnostic validity of the CRIES is still insufficient, has been restricted to specific populations, and sample sizes have often been small. This study evaluated the reliability and validity of the 8-item (CRIES-8) and 13-item (CRIES-13) versions of the CRIES in a large clinically referred sample. The measure was completed by 395 Dutch children (7-18 years) who had experienced a wide variety of traumatic events. PTSD was assessed using the Anxiety Disorders Interview Schedule for DSM-IV: Child and Parent version. A cutoff score of 17 on the CRIES-8 and 30 on the CRIES-13 emerged as the best balance between sensitivity and specificity, and correctly classified 78%-81% of all children. The CRIES-13 outperformed the CRIES-8, in that the overall efficiency of the CRIES-13 was slightly superior (.81 and .78, respectively). The CRIES appears to be a reliable and valid measure, which gives clinicians a brief and user-friendly instrument to identify children who may have PTSD and offer them appropriate and timely treatment., (Copyright © 2014 International Society for Traumatic Stress Studies.)

Background: Recommended therapy duration for patients hospitalized with cellulitis is 10-14 days. Unnecessary use of antibiotics is one of the key factors driving resistance. Recent studies have shown that antibiotic therapy for cellulitis in outpatients can safely be shortened, despite residual inflammation. This study will compare in hospitalized patients the safety and effectiveness of shortening antibiotic therapy for cellulitis from 12 to 6 days., Methods/design: In a multicenter, randomized, double-blind, non-inferiority trial, adult patients admitted with cellulitis will be included. Cellulitis is defined as warmth, erythema, and induration of the skin and/or subcutaneous tissue, with or without pain (including erysipelas). All patients will initially be treated with intravenous flucloxacillin, and will be evaluated after 5-6 days. Those who have improved substantially (defined as being afebrile, and having a lower cellulitis severity score) will be randomized at day 6 between additional 6 days of oral flucloxacillin (n = 198) or placebo (n = 198). Treatment success is defined as resolution of cellulitis on day 14 (disappearance of warmth and tenderness, improvement of erythema and edema), without the need of additional antibiotics for cellulitis by day 28. Secondary endpoints are relapse rate (up to day 90), speed of recovery (using a cellulitis severity score until day 28, and VAS scores on pain and swelling until day 90), quality of life (using the SF-36 and EQ-5D questionnaires) and costs (associated with total antibiotic use and health-care resource utilization up to day 90)., Discussion: Inclusion is planned to start in Q2 2014., Trial Registration: ClinicalTrials.gov (NCT02032654) and the Netherlands Trial Register (NTR4360).

Objective: Women with late preterm premature rupture of membranes (PROM) have an increased risk that their child will develop neonatal sepsis. We evaluated whether neonatal sepsis can be predicted from antepartum parameters in these women., Study Design: We used multivariable logistic regression to develop a prediction model. Data were obtained from two recent randomized controlled trials on induction of labor versus expectant management in late preterm PROM (PPROMEXIL trials, (ISRCTN29313500 and ISRCTN05689407). Data from randomized as well as non-randomized women, who consented to the use of their medical data, were used. We evaluated 13 potential antepartum predictors for neonatal sepsis. Missing data were imputed. Discriminative ability of the model was expressed as the area under the receiver operating characteristic (ROC) curve and a calibration with both a calibration plot and the Hosmer and Lemeshow goodness-of-fit test. Overall performance of the prediction model was quantified as the scaled Brier score., Results: We studied 970 women. Thirty-three (3.4%) neonates suffered neonatal sepsis. Maternal age (OR 1.09 per year), maternal CRP level (OR 1.01 per mmol/l), maternal temperature (OR 1.80 per °C) and positive GBS culture (OR 2.20) were associated with an increased risk of neonatal sepsis. The model had an area under the ROC-curve of 0.71. The model had both a good calibration and accuracy., Conclusions: Antepartum parameters aid in the more precise prediction of the risk of neonatal sepsis in women with late preterm PPROM., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: To compare the costs of induction of labor and expectant management in women with preterm prelabor rupture of membranes (PPROM)., Design: Economic analysis based on a randomized clinical trial., Setting: Obstetric departments of eight academic and 52 non-academic hospitals in the Netherlands., Population: Women with PPROM near term who were not in labor 24 h after PPROM., Methods: A cost-minimization analysis was done from a health care provider perspective, using a bottom-up approach to estimate resource utilization, valued with unit-costs reflecting actual costs., Main Outcome Measures: Primary health outcome was the incidence of neonatal sepsis. Direct medical costs were estimated from start of randomization to hospital discharge of mother and child., Results: Induction of labor did not significantly reduce the probability of neonatal sepsis [2.6% vs. 4.1%, relative risk 0.64 (95% confidence interval 0.25-1.6)]. Mean costs per woman were €8094 for induction and €7340 for expectant management (difference €754; 95% confidence interval -335 to 1802). This difference predominantly originated in the postpartum period, where the mean costs were €5669 for induction vs. €4801 for expectant management. Delivery costs were higher in women allocated to induction than in women allocated to expectant management (€1777 vs. €1153 per woman). Antepartum costs in the expectant management group were higher because of longer antepartum maternal stays in hospital., Conclusions: In women with pregnancies complicated by PPROM near term, induction of labor does not reduce neonatal sepsis, whereas costs associated with this strategy are probably higher., (© 2014 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background: Heavy menstrual bleeding (HMB) and post-menopausal bleeding (PMB) together constitute the commonest gynaecological presentation in secondary care and impose substantial demands on health service resources. Accurate diagnosis is of key importance to realising effective treatment, reducing morbidity and, in the case of PMB, reducing mortality. There are many tests available, including transvaginal scan (TVS), endometrial biopsy (EBx), saline infusion sonography and outpatient hysteroscopy (OPH); however, optimal diagnostic work-up is unclear., Objectives: To determine the most cost-effective diagnostic testing strategy for the diagnosis and treatment of (i) HMB and (ii) PMB., Data Sources: Parameter inputs were derived from systematic quantitative reviews, individual patient data (IPD) from existing data sets and focused searches for specific data. In the absence of data estimates, the consensus view of an expert clinical panel was obtained., Methods: Two clinically informed decision-analytic models were constructed to reflect current service provision for the diagnostic work-up of women presenting with HMB and PMB. The model-based economic evaluation took the form of a cost-effectiveness analysis from the perspective of the NHS in a contemporary, 'one-stop' secondary care clinical setting, where all indicated testing modalities would be available during a single visit., Results: Two potentially cost-effective testing strategies for the initial investigation of women with HMB were identified: OPH alone or in combination with EBx. Although a combination testing strategy of OPH + EBx was marginally more effective, the incremental cost-effectiveness ratio (ICER) was approximately £21,000 to gain one more satisfied patient, whereas for OPH it was just £360 when compared with treatment with the levonorgestrel intrauterine system (LNG-IUS) without investigation. Initial testing with OPH was the most cost-effective testing approach for women wishing to preserve fertility and for women with symptoms refractory to empirical treatment with a LNG-IUS. For the investigation of PMB, selective use of TVS based on historical risk prediction for the diagnostic work-up of women presenting with PMB generated an ICER compared with our reference strategy of 'no initial work-up' of £129,000 per extra woman surviving 5 years. The ICERs for the two other non-dominated testing strategies, combining history and TVS or combining OPH and TVS, were over £2M each., Limitations: In the absence of IPD, estimates of accuracy for test combinations presented some uncertainty where test results were modelled as being discordant., Conclusions: For initial investigation of women presenting to secondary care with HMB who do not require preservation of their fertility, our research suggests a choice between OPH alone or a combination of OPH and EBx. From our investigation, OPH appears to be the optimal first-line diagnostic test used for the investigation of women presenting to secondary care with HMB wishing to preserve their fertility or refractory to previous medical treatment with the LNG-IUS. We would suggest that the current recommendation of basing the initial investigation of women with PMB on the universal TVS measurement of endometrial thickness at a 5-mm threshold may need to be replaced by a strategy of restricting TVS to women with risk factors (e.g. increasing age-raised body mass index, diabetes or nulliparity), obtained from the preceding clinical assessment., Funding: The National Institute for Health Research Health Technology Assessment programme.

Background: Preterm birth is the most common cause of neonatal morbidity and mortality. Postponing delivery for 48 hours with tocolytics to allow for maternal steroid administration and antenatal transportation to a centre with neonatal intensive care unit facilities is the standard treatment for women with threatening preterm delivery in most centres. However, there is controversy as to which tocolytic agent is the drug of first choice. Previous trials have focused on tocolytic efficacy and side effects, and are probably underpowered to detect clinically meaningfull differences in neonatal outcome. Thus, the current evidence is inconclusive to support a balanced recommendation for clinical practice. This multicenter randomised clinical trial aims to compare nifedipine and atosiban in terms of neonatal outcome, duration of pregnancy and maternal side effects., Methods/design: The Apostel III trial is a nationwide multicenter randomised controlled study. Women with threatened preterm labour (gestational age 25 - 34 weeks) defined as at least 3 contractions per 30 minutes, and 1) a cervical length of ≤ 10 mm or 2) a cervical length of 11-30 mm and a positive Fibronectin test or 3) ruptured membranes will be randomly allocated to treatment with nifedipine or atosiban. Primary outcome is a composite measure of severe neonatal morbidity and mortality. Secondary outcomes will be time to delivery, gestational age at delivery, days on ventilation support, neonatal intensive care (NICU) admittance, length admission in neonatal intensive care, total days in hospital until 3 months corrected age, convulsions, apnoea, asphyxia, proven meningitis, pneumothorax, maternal side effects and costs. Furthermore, an economic evaluation of the treatment will be performed. Analysis will be by intention to treat principle. The power calculation is based on an expected 10% difference in the prevalence of adverse neonatal outcome. This implies that 500 women have to be randomised (two sided test, β 0.2 at alpha 0.05)., Discussion: This trial will provide evidence on the optimal drug of choice in acute tocolysis in threatening preterm labour., Clinical Trial Registration: NTR2947, date of registration: June 20th 2011.

Objective: guidelines recommend that external cephalic version (ECV) should be offered to all women with a fetus in breech presentation at term. However, only 50-60% of the women receive an ECV attempt. We explored the determinants (barriers and facilitators) affecting the uptake of the guidelines among gynaecologists and midwives in the Netherlands., Design: national online survey., Setting: the Netherlands., Participants: gynaecologists and midwives., Measurements: in the online survey, we identified the determinants that positively or negatively influenced the professionals׳ adherence to three key recommendations in the guidelines: (a) counselling, (b) advising for ECV, (c) arranging an ECV. Determinants were identified in a previously performed qualitative study and were categorised into five underlying constructs; attitude towards ECV, professional obligation, outcome expectations, self-efficacy and preconditions for successful ECV. We performed a multivariate analysis to assess the importance of the different constructs for adherence to the guideline., Findings: 364 professionals responded to the survey. Adherence varied: 84% counselled, 73% advised, and 82% arranged an ECV for (almost) all their clients. Although 90% of respondents considered ECV to be an effective treatment for preventing caesarean childbirths, only 30% agreed that 'every client should undergo ECV'. Self-efficacy (perceived skills) was the most important determinant influencing adherence., Key Conclusions: self-efficacy appears to be the most significant determinant for counselling, advising and arranging an ECV., Implications for Practice: to improve adherence to the guidelines on ECV we must improve self-efficacy., (Copyright © 2014. Published by Elsevier Ltd.)

Objective: external cephalic version (ECV) is a relatively simple and safe manoeuvre and a proven effective approach in the reduction of breech presentation at term. There is professional consensus that ECV should be offered to all women with a fetus in breech presentation, but only up to 70% of women eligible for ECV undergo an ECV attempt. The aim of the study was to identify barriers and facilitators for ECV among professionals and women with a breech presentation at term., Design: qualitative study with semi-structured interviews., Setting: Dutch hospitals., Participants: pregnant women with a breech presentation who had decided on ECV, and midwives and gynaecologists treating women with a breech presentation., Measurements: on the basis of national guidelines and expert opinions, we developed topic lists to guide the interviews and discuss barriers and facilitators in order to decide on ECV (pregnant women) or advice on ECV (midwives and gynaecologists)., Findings: among pregnant women the main barriers were fear, the preference to have a planned caesarean section (CS), incomplete information and having witnessed birth complications within the family or among friends. The main facilitators were the wish for a home birth, the wish for a vaginal delivery and confidence of the safety of ECV. Among professionals the main barriers were a lack of knowledge to fully inform and counsel patients on ECV, and the inability to counsel women who preferred a primary CS. The main facilitator was an unambiguous policy on (counselling for) ECV within the region., Conclusion: we identified several barriers and facilitators possibly explaining the suboptimal implementation of ECV for breech presentation in the Netherlands. This knowledge should be taken into account in designing implementation strategies for ECV to improve the uptake of ECV by professionals and patients., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Approximately 15-20% of all clinically confirmed pregnancies end in a miscarriage. Intrauterine adhesions (IUAs) are a possible complication after miscarriage, but their prevalence and the contribution of possible risk factors have not been elucidated yet. In addition, the long-term reproductive outcome in relation to IUAs has to be elucidated., Methods: We systematically searched the literature for studies that prospectively assessed the prevalence and extent of IUAs in women who suffered a miscarriage. To be included, women diagnosed with a current miscarriage had to be systematically evaluated within 12 months by hysteroscopy after either spontaneous expulsion or medical or surgical treatment. Studies that included women with a history of recurrent miscarriage only or that evaluated the IUAs after elective abortion or beyond 12 months after the last miscarriage were not included. Subsequently, long-term reproductive outcomes after expectant (conservative), medical or surgical management were assessed in women with and without post-miscarriage IUAs., Results: We included 10 prospective studies reporting on 912 women with hysteroscopic evaluation within 12 months of miscarriage and 8 prospective studies, including 1770 women, reporting long-term reproductive outcome. IUAs were detected in 183 women, resulting in a pooled prevalence of 19.1% [95% confidence interval (CI): 12.8-27.5%]. The extent of IUAs was reported in 124 women (67.8%) and was mild, moderate and severe respectively in 58.1, 28.2 and 13.7% of cases. Relative to women with one miscarriage, women with two or three or more miscarriages showed an increased risk of IUAs by a pooled OR of 1.41 and 2.1, respectively. The number of dilatation and curettage (D&C) procedures seemed to be the main driver behind these associations. A total of 150 congenital and acquired intrauterine abnormalities were encountered in 675 women, resulting in a pooled prevalence of 22.4% (95% CI: 16.3-29.9%). Similar reproductive outcomes were reported subsequent to conservative, medical or surgical management for miscarriage, although the numbers of studies and of included women were limited. No studies reported long-term reproductive outcomes following post-miscarriage IUAs., Conclusions: IUAs are frequently encountered, in one in five women after miscarriage. In more than half of these, the severity and extent of the adhesions was mild, with unknown clinical relevance. Recurrent miscarriages and D&C procedures were identified as risk factors for adhesion formation. Congenital and acquired intrauterine abnormalities such as polyps or fibroids were frequently identified. There were no studies reporting on the link between IUAs and long-term reproductive outcome after miscarriage, while similar pregnancy outcomes were reported subsequent to conservative, medical or surgical management. Although this review does not allow strong clinical conclusions on treatment management, it signals an important clinical problem. Treatment strategies are proposed to minimize the number of D&C in an attempt to reduce IUAs.

Objective: The objective of the study was to evaluate the cost-effectiveness of risk stratification with cervical length (CL) measurement and/or fetal fibronectin (fFN) tests in women with threatened preterm labor between 24 and 34 weeks' gestation., Study Design: We performed a model-based cost-effectiveness analysis to evaluate 7 test-treatment strategies in women with threatened preterm labor from a health care system perspective. Estimates on disease prevalence, costs, and test accuracy were based on medical literature., Results: We found that additional fFN testing in the case of a CL between 10 and 30 mm is cost saving without compromising neonatal health outcomes, compared with a treat-all strategy or single CL testing. Implementing this strategy could lead to an annual cost saving between €2.8 million and €14.4 million in The Netherlands, a country with about 180,000 deliveries annually., Conclusion: In women with threatened preterm labor between 24 and 34 weeks of gestation, the most cost-effective test strategy uses a combination of CL and fFN testing., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: To perform a systematic review and meta-analysis to assess the predictive capacity of transvaginal sonographic assessment of the cervix for the outcome of induction of labor., Methods: We searched MEDLINE, EMBASE and the Cochrane Library, and manually searched reference lists of review articles and eligible primary articles. Studies in all languages were eligible if published in full. Two reviewers independently selected studies and extracted data on study characteristics, quality and test accuracy. We then calculated pooled sensitivities and specificities (with 95% CIs) and summary receiver-operating characteristics (sROC) curves. Outcome measures were test accuracy of sonographically measured cervical length and cervical wedging for Cesarean section, not achieving vaginal delivery within 24 h and not achieving active labor., Results: We included 31 studies reporting on both cervical length and outcome of delivery. The quality of the included studies was mediocre. Sensitivity of cervical length in the prediction of Cesarean delivery ranged from 0.14 to 0.92 and specificity ranged from 0.35 to 1.00. The estimated sROC curve for cervical length indicated a limited predictive capacity in the prediction of Cesarean delivery. Summary estimates of sensitivity/specificity combinations of cervical length at different cut-offs for Cesarean delivery were 0.82/0.34, 0.64/0.74 and 0.13/0.95 for 20, 30 and 40 mm, respectively. For cervical wedging in the prediction of failed induction of labor summary point estimates of sensitivity/specificity were 0.37/0.80., Conclusions: Cervical length and cervical wedging as measured sonographically at or near term have moderate capacity to predict the outcome of delivery after induction of labor., (Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.)

Background: A medical tests may influence the health of patients by guiding clinical decisions, such as treatment in case of a positive test result. However, a medical test can influence the health of patients through other mechanisms as well, like giving reassurance. To make a clinical recommendation about a medical test, we should be aware of the full range of effects of that test on patients. This requires an understanding of the range of effects that medical testing can have on patients. This study evaluates the mechanisms through which medical testing can influence patients' health, other than the effect on clinical management, from a gynecologist's perspective., Methods: A qualitative study in which explorative focus groups were conducted with gynecologists, gynecological residents and gynecological M.D. researchers (n = 43). Discussions were transcribed verbatim. Transcriptions were coded inductively and analyzed by three researchers., Results: All participants contributed various clinical examples in which medical testing had influenced patients' health. Clinical examples illustrated that testing, in itself or in interaction with contextual factors, may provoke a wide range of effects on patients. Our data showed that testing can influence the doctor's perceptions of the patients' appraisal of their illness, their perceived control, or the doctor-patient relationship. This may lead to changes in psychological, behavioral, and/or medical outcomes, both favorably or unfavorably. The data were used to construct a conceptual framework of effects of medical testing on patients., Conclusions: Besides supporting clinical decision making, medical testing may have favorable or unfavorable effects on patients' health though several mechanisms.

Objective: To determine which doctor- and patient-related factors affect failure of outpatient endometrial sampling in women with postmenopausal bleeding, and to develop a multivariable prediction model to select women with a high probability of failed sampling., Design: Prospective multicenter cohort study., Setting: Three teaching hospitals in the Netherlands., Population: Women presenting with postmenopausal bleeding with an indication for endometrial sampling., Methods: Multivariable logistic regression was performed to evaluate the impact of doctor's training level and patient's characteristics on failure of sampling., Main Outcome Measures: Failure of endometrial sampling, classified as technical failure or insufficient tissue for diagnosis., Results: In 74 (20.8%) of the 356 included women, sampling technically failed, and in 84 (29.8%) the amount of tissue was insufficient for diagnosis. Nulliparity [odds ratio (OR) 3.8, 95% confidence interval (CI) 1.8-7.9] and advanced age (OR 1.03 per year, 95% CI 1.00-1.06) were associated with technical failure. Advanced age was associated with insufficient sampling (OR 1.04 per year, 95% CI 1.01-1.07), and endometrial thickness >12 mm decreased the chance of insufficient sampling (OR 0.3, 95%CI 0.1-0.8). The prediction model for total failure had an area under the ROC curve of 0.64 (95% CI 0.58-0.70)., Conclusions: In women with postmenopausal bleeding, the failure rate of endometrial sampling is relatively high and is associated with nulliparity and advanced age. Endometrial thickness >12 mm decreased the chance of failure. A multivariable prediction model for total failure based on patient characteristics has a moderate capacity to discriminate between women at high or low risk of failure., (© 2013 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: Pregnancies complicated by intrauterine growth restriction (IUGR) are at increased risk for neonatal morbidity and mortality. The Dutch nationwide disproportionate intrauterine growth intervention trial at term (DIGITAT trial) showed that induction of labour and expectant monitoring were comparable with respect to composite adverse neonatal outcome and operative delivery. In this study we compare the costs of both strategies., Study Design: A cost analysis was performed alongside the DIGITAT trial, which was a randomized controlled trial in which 650 women with a singleton pregnancy with suspected IUGR beyond 36 weeks of pregnancy were allocated to induction or expectant management. Resource utilization was documented by specific items in the case report forms. Unit costs for clinical resources were calculated from the financial reports of participating hospitals. For primary care costs Dutch standardized prices were used. All costs are presented in Euros converted to the year 2009., Results: Antepartum expectant monitoring generated more costs, mainly due to longer antepartum maternal stays in hospital. During delivery and the postpartum stage, induction generated more direct medical costs, due to longer stay in the labour room and longer duration of neonatal high care/medium care admissions. From a health care perspective, both strategies generated comparable costs: on average €7106 per patient for the induction group (N=321) and €6995 for the expectant management group (N=329) with a cost difference of €111 (95%CI: €-1296 to 1641)., Conclusion: Induction of labour and expectant monitoring in IUGR at term have comparable outcomes immediately after birth in terms of obstetrical outcomes, maternal quality of life and costs. Costs are lower, however, in the expectant monitoring group before 38 weeks of gestation and costs are lower in the induction of labour group after 38 weeks of gestation. So if induction of labour is considered to pre-empt possible stillbirth in suspected IUGR, it is reasonable to delay until 38 weeks, with watchful monitoring., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: To assess the ability of the Bishop score to predict the mode of delivery in women scheduled for induction of labor at term., Study Design: We performed a systematic literature search of electronic databases from inception to July 2009. Studies reporting on both the Bishop score and the outcome of labor in women scheduled for induction of labor at term were eligible. We used a bivariate model to estimate a summary receiver operating characteristic (sROC) curve for the outcome cesarean delivery., Results: We included 40 primary articles reporting on 13,757 women. Study quality was mediocre. The sROC curve of the Bishop score in the prediction of cesarean delivery indicated a poor predictive capacity. For the prediction of cesarean delivery, the sensitivity-specificity combinations were 47%-75%, 61%-53% and 78%-44% for the Bishop scores of 4, 5, and 6, respectively. For a Bishop score below 9, the sensitivity-specificity combination was 95%-30%., Conclusion: The Bishop score is a poor predictor for the outcome of induced labor at term and should not be used to decide whether to induce labor or not., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: The Diagnostic and Statistical Manual of Mental Disorders (DSM)-Criteria A1 and A2 for posttraumatic stress disorder (PTSD) have been discussed extensively, with several studies in adults or adolescents supporting the removal of Criterion A2. However, solid research in children is missing., Objective: This study evaluated the DSM-Criteria A1 and A2 in predicting posttraumatic stress in children., Method: A sample of 588 Dutch school children, aged 8-18 years, completed a self-report questionnaire to determine if they met Criteria A1 and/or A2. Their posttraumatic stress response was assessed using the Children's Revised Impact of Event Scale., Results: The contribution of Criterion A2 to the prediction of posttraumatic stress in children is of greater importance than the contribution of Criterion A1. Children who met Criterion A2 reported significantly higher levels of posttraumatic stress and were nine times more likely to develop probable PTSD than children who did not meet Criterion A2. When Criterion A1 was met, a child was only two times more likely to develop probable PTSD as compared with those where Criterion A1 was not met. Furthermore, the low sensitivity of Criterion A1 suggests that children may regularly develop severe posttraumatic stress in the absence of Criterion A1. The remarkably high negative predictive value of Criterion A2 indicates that if a child does not have a subjective reaction during an event that it is unlikely that he or she will develop PTSD., Conclusions: In contrast to most adult studies, the findings of this study emphasize the significant contribution of Criterion A2 to the prediction of posttraumatic stress in children and raise fundamental questions about the value of the current Criterion A1.

Objective: To evaluate whether ovarian reserve tests (ORTs) add prognostic value to patient characteristics, such as female age, in the prediction of excessive response to ovarian hyperstimulation in patients undergoing IVF, and whether their performance differs across clinical subgroups., Design: Authors of studies reporting on basal FSH, antimüllerian hormone (AMH), or antral follicle count (AFC) in relation to ovarian response to ovarian hyperstimulation were invited to share original data. Random intercept logistic regression models were used to estimate added value of ORTs on patient characteristics, while accounting for between-study heterogeneity. Receiver operating characteristic regression analyses were performed to study the effect of patient characteristics on ORT accuracy., Setting: In vitro fertilization clinics., Patient(s): A total of 4,786 women for the main analysis, with a subgroup of 1,023 women with information on all three ORTs., Intervention(s): None., Main Outcome Measure(s): Excessive response prediction., Result(s): We included 57 studies reporting on 32 databases. Female age had an area under the receiver operating characteristic curve of 0.61 for excessive response prediction. Antral follicle count and AMH significantly added prognostic value to this. A model with female age, AFC, and AMH had an area under the receiver operating characteristic curve of 0.85. The combination of AMH and AFC, without age, had similar accuracy. Subgroup analysis indicated that FSH performed significantly worse in predicting excessive response in higher age groups, AFC did significantly better, and AMH performed the same., Conclusion(s): We demonstrate that AFC and AMH add value to female age in the prediction of excessive response and that, for AFC and FSH, the discriminatory performance is affected by female age., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the accuracy of antenatal sonographic measurement of lower uterine segment (LUS) thickness in the prediction of risk of uterine rupture during a trial of labor (TOL) in women with a previous Cesarean section (CS)., Methods: PubMed and EMBASE were searched to identify articles published on the subject of sonographic LUS measurement and occurrence of a uterine defect after delivery. Four independent researchers performed identification of papers and data extraction. Selected studies were scored on methodological quality, and sensitivity and specificity of measurement of LUS thickness in the prediction of a uterine defect were calculated. We performed bivariate meta-analysis to estimate summary receiver-operating characteristics (sROC) curves., Results: We included 21 studies with a total of 2776 analyzed patients. The quality of included studies was good, although comparison was difficult because of heterogeneity. The estimated sROC curves showed that measurement of LUS thickness seems promising in the prediction of occurrence of uterine defects (dehiscence and rupture) in the uterine wall. The pooled sensitivity and specificity of myometrial LUS thickness for cut-offs between 0.6 and 2.0 mm was 0.76 (95% CI, 0.60-0.87) and 0.92 (95% CI, 0.82-0.97); cut-offs between 2.1 and 4.0 mm reached a sensitivity and specificity of 0.94 (95% CI, 0.81-0.98) and 0.64 (95% CI, 0.26-0.90). The pooled sensitivity and specificity of full LUS thickness for cut-offs between 2.0 and 3.0 mm was 0.61 (95% CI, 0.42-0.77) and 0.91 (95% CI, 0.80-0.96); cut-offs between 3.1 and 5.1 mm reached a sensitivity and specificity of 0.96 (95% CI, 0.89-0.98) and 0.63 (95% CI, 0.30-0.87)., Conclusions: This meta-analysis provides support for the use of antenatal LUS measurements in the prediction of a uterine defect during TOL. Clinical applicability should be assessed in prospective observational studies using a standardized method of measurement., (Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To assess the economic consequences of labour induction with Foley catheter compared to prostaglandin E2 gel., Design: Economic evaluation alongside a randomised controlled trial., Setting: Obstetric departments of one university and 11 teaching hospitals in the Netherlands., Population: Women scheduled for labour induction with a singleton pregnancy in cephalic presentation at term, intact membranes and an unfavourable cervix; and without previous caesarean section., Methods: Cost-effectiveness analysis from a hospital perspective., Main Outcome Measures: We estimated direct medical costs associated with healthcare utilisation from randomisation to 6 weeks postpartum. For caesarean section rate, and maternal and neonatal morbidity we calculated the incremental cost-effectiveness ratios, which represent the costs to prevent one of these adverse outcomes., Results: Mean costs per woman in the Foley catheter group (n = 411) and in the prostaglandin E₂ gel group (n = 408), were €3297 versus €3075, respectively, with an average difference of €222 (95% confidence interval -€157 to €633). In the Foley catheter group we observed higher costs due to longer labour ward occupation and less cost related to induction material and neonatal admissions. Foley catheter induction showed a comparable caesarean section rate compared with prostaglandin induction, therefore the incremental cost-effectiveness ratio was not informative. Foley induction resulted in fewer neonatal admissions (incremental cost-effectiveness ratio €2708) and asphyxia/postpartum haemorrhage (incremental cost-effectiveness ratios €5257) compared with prostaglandin induction., Conclusions: Foley catheter and prostaglandin E2 labour induction generate comparable costs., (© 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.)

Objective: To determine and compare the diagnostic accuracy of the lecithin/sphingomyelin (L/S) ratio and lamellar body count (LBC) in the prediction of neonatal respiratory distress syndrome (RDS)., Study Design: A systematic review was performed to identify studies comparing either the L/S ratio or the LBC with the occurrence of RDS published between January 1999 and February 2009. Two independent reviewers performed study selection and data extraction. For each study sensitivity and specificity were calculated. Summary receiver-operating characteristics (ROC) curves, assessing the diagnostic performance of both tests, were constructed. A subgroup analysis was performed to estimate the sensitivity and specificity of the various cut-off values., Results: 13 studies were included. The ROC curves of the collected data illustrate that the LBC and L/S ratio perform equally well in the prediction of RDS. Comparison of the two summary ROC curves of each test indicates that the diagnostic performance of LBC might even have a slight advantage over L/S ratio. Due to the wide cut-off range it was not possible to define specific cut-off values with the best accuracy., Conclusion: We recommend replacing the L/S ratio as gold standard with the lamellar body count since the LBC is easy to perform, rapid, inexpensive, and available to all hospitals 24h per day., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Medical treatment with misoprostol is a non-invasive and inexpensive treatment option in first trimester miscarriage. However, about 30% of women treated with misoprostol have incomplete evacuation of the uterus. Despite being relatively asymptomatic in most cases, this finding often leads to additional surgical treatment (curettage). A comparison of effectiveness and cost-effectiveness of surgical management versus expectant management is lacking in women with incomplete miscarriage after misoprostol., Methods/design: The proposed study is a multicentre randomized controlled trial that assesses the costs and effects of curettage versus expectant management in women with incomplete evacuation of the uterus after misoprostol treatment for first trimester miscarriage.Eligible women will be randomized, after informed consent, within 24 hours after identification of incomplete evacuation of the uterus by ultrasound scanning. Women are randomly allocated to surgical or expectant management. Curettage is performed within three days after randomization.Primary outcome is the sonographic finding of an empty uterus (maximal diameter of any contents of the uterine cavity < 10 millimeters) six weeks after study entry. Secondary outcomes are patients' quality of life, surgical outcome parameters, the type and number of re-interventions during the first three months and pregnancy rates and outcome 12 months after study entry., Discussion: This trial will provide evidence for the (cost) effectiveness of surgical versus expectant management in women with incomplete evacuation of the uterus after misoprostol treatment for first trimester miscarriage., Trial Registration: Dutch Trial Register: NTR3110.

Objective: To evaluate the methodologic quality of economic analyses published in the field of reproductive medicine., Design: Systematic review., Setting: Centers for reproductive care., Patient(s): Infertility patients., Intervention(s): We performed a Medline search to identify economic evaluation studies in reproductive medicine. We included studies that concerned interventions, evaluated costs and effects, and were published in a journal on reproductive medicine, gynecology, or a major general journal from 1997 through May 2011., Main Outcome Measure(s): Number of quality criteria adhered to., Result(s): Our search revealed 5,519 articles, of which 85 met our inclusion criteria. Seventy-seven (91%) of the economic analyses were on treatment, six (7%) on diagnosis, and two (2%) on screening. The mean number of quality criteria adhered to was 20 out of 30 items, and only one article met all 30 criteria. The mean number of criteria adhered to was higher if at least one of the authors was from a methodologic or health economics department (mean 23 [n = 30] versus mean 20 [n = 55]). The most common limitations of published economic evaluation studies were in methodology or presentation of incremental analyses, sensitivity analyses, and discounting., Conclusion(s): Economic analyses published in the past 15 years in the field of reproductive medicine seldom adhere to all recommended methodologic standards. A large majority of these publications evaluated treatments rather than diagnostic interventions., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

We evaluated the methodological quality of economic evaluation studies in the field of obstetrics and gynecology published in the last decade. A MEDLINE search was performed to find economic evaluation studies in obstetrics and gynecology from the years 1997 through 2009. We included full economic evaluation studies concerning tests or interventions in the field of obstetrics or gynecology. Each included study was evaluated by two reviewers using a quality checklist that was based on international guidelines for medical economic evaluation studies and a checklist used in a previous review. The mean number of quality criteria adhered to was 23 of 30 items, whereas five articles (3%) met all 30 criteria. Compliance was low for the description of the perspective (40%), the completeness of costs looking at the perspective (48%) or time horizon (48%), and reporting of quantities of resources (47%). Furthermore, if no discounting was applied, an explanation was infrequently given (14%). A comparison of study quality to that reported by Smith and Blackmore showed a considerable improvement in the following criteria: presentation perspective (from 19 to 40%), statement of primary outcome measure (from 72 to 81%), completeness costs looking at the time horizon (from 14 to 48%), the presentation of discount rates (from 10 to 54%), details of sensitivity analyses (from 21 to 61%), reporting incremental results (from 17 to 70%), and reporting a summary measure (from 57 to 74%). The quality of economic studies in obstetrics and gynecology has considerably improved in the last decade, but room for further improvement is present., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective. The aim of this study was to assess whether cervical length measurement (CL) could predict preterm birth (PTB) in symptomatic women with a twin pregnancy. Methods. We searched MEDLINE and EMBASE to identify studies investigating the accuracy of CL measurement in predicting PTB in symptomatic women with a twin pregnancy. We extracted data to construct two-by-two tables and used bivariate meta-analysis to generate point estimates of sensitivity and specificity. Results. Five studies (N = 226) were included. Variation in definition of PTB and cut-off points for CL was strong. One study investigated delivery within seven days, demonstrating a sensitivity of 1.0 (95% CI: 0.83-1.0) and a specificity of 0.31 (95% CI 0.2-0.43) for a CL cutoff at 25 mm. Three studies reported on predicting PTB < 37 weeks at a CL cutoff of 30 mm, with sROC point estimates of 0.76 (95% CI: 0.66 to 0.84) and 0.37 (95% CI: 0.21 to 0.56) for sensitivity and specificity, respectively. For preterm birth <34 weeks, no pooled estimates could be estimated since only 2 studies with large heterogeneity were identified. Conclusions. There is limited evidence on the accuracy of cervical length measurement testing the prediction of preterm birth in symptomatic women with a twin pregnancy, especially on the most important outcome, that is, delivery within 7 days.

Objective: To gain an insight into the costs and health outcomes of effectiveness studies in obstetrics at a national level., Design: Budget impact analysis., Method: We searched for obstetric effectiveness studies. The possible budget impact of implementation in all patients in the Netherlands was calculated, as well as health benefits for mothers and their children., Results: We used eight multicentre randomized trials with almost 11,000 patients in total. The total potential cost reduction for these trials was € 9.6 million per year, on the basis of a one-time investment in the trials of € 3.1 million. When implementing the results of these studies, a health benefit is shown in women with hypertension or pre-eclampsia at term, women in whom labour is induced and women with fetal monitoring. This also applied to the children of these women. Furthermore, removal or non-implementation of interventions that have no positive effect on health such as prolonged tocolysis, the use of progestogens in twin pregnancies, intrauterine pressure catheters, and induction of labour in preterm ruptured membranes reduces care costs., Conclusion: Adequate application of the results of effectiveness studies in obstetrics should result in considerable health gains and cost reduction when compared with provision of non-scientifically supported care.

Background: Although the hope is that many perinatal interventions are performed with an ultimate aim to improve the long-term health and development of the child, long-term outcome is rarely used as a primary end-point in perinatal randomised controlled trials (RCTs)., Objective: To evaluate how often and with which tools long-term follow-up is performed after large obstetric RCTs., Search Strategy: We searched the Cochrane Library for Cochrane reviews published by the Cochrane Pregnancy and Childbirth Group for reviews on interventions that aimed to improve neonatal outcome. Selection criteria  Reviews on perinatal interventions that were not performed to improve the condition of the neonate were excluded. We limited our review to RCTs with more than 350 participating women. For each included study, we checked in Web of Science as to whether the researchers had reported on follow-up in subsequent publications., Data Collection and Analysis: Relevant information was extracted from these RCTs by two reviewers using a predefined data collection sheet. All information was analysed using SPSS 17.0 (SPSS Inc., Chicago, IL, USA)., Main Results: We studied 212 reviews including 1837 RCTs on perinatal interventions, 249 (14%) of which included 350 participants. Only 40 of 249 RCTs (16%) followed the children after discharge from the hospital to evaluate the effect of a specific perinatal intervention. The number of RCTs with long-term follow-up remained stable, with 10 of 67 RCTs (15%) reporting follow-up before 1990, 17 of 115 (15%) between 1990 and 2000, and 13 of 67 (19%) after 2000 (P = 0.68)., Conclusions: Only a small minority of large perinatal RCTs report the long-term follow-up of the child. Future obstetric RCTs should consider performing long-term follow-up at the start of the trial., (© 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.)

BACKGROUND Although ovarian reserve tests (ORTs) are frequently used prior to IVF treatment for outcome prediction, their added predictive value is unclear. We assessed the added value of ORTs to patient characteristics in the prediction of IVF outcome. METHODS An individual patient data (IPD) meta-analysis from published studies was performed. Studies on FSH, anti-Müllerian hormone (AMH) or antral follicle count (AFC) in women undergoing IVF were identified and authors were contacted. Using random intercept logistic regression models, we estimated the added predictive value of ORTs for poor response and ongoing pregnancy after IVF, relative to patient characteristics. RESULTS We were able to collect 28 study databases, comprising 5705 women undergoing IVF. The area under the receiver-operating characteristic curve (AUC) for female age in predicting poor response was 0.61. AFC and AMH each significantly improved the model fit (P-value <0.001). Moreover, almost a similar accuracy was reached using AMH or AFC alone (AUC 0.78 and 0.76, respectively). Combining the two tests, however, did not improve prediction (AUC 0.80, P = 0.19) of poor response. In predicting ongoing pregnancy after IVF, age was the best single predictor (AUC 0.57), and none of the ORTs added any value. CONCLUSIONS This IPD meta-analysis demonstrates that AFC and AMH clearly add to age in predicting poor response. As single tests, AFC and AMH both fully cover the prediction of poor ovarian response. In contrast, none of the ORTs add any information to the limited capacity of female age to predict ongoing pregnancy after IVF. The clinical usefulness of ORTs prior to IVF will be limited to the prediction of ovarian response.

Objectives: Measurement of endometrial thickness is an important tool in the assessment of women with postmenopausal bleeding, but the role of endometrial thickness measurement by ultrasound in asymptomatic women is unclear. The aims of this study were to determine: (1) the normal endometrial thickness measured by ultrasonography, (2) the prevalence of serious endometrial pathology and (3) the sensitivity and specificity of endometrial thickness measurement by transvaginal ultrasonography (TVS) for diagnosing premalignant and malignant endometrial disease in asymptomatic postmenopausal women., Methods: A MEDLINE and EMBASE search (from inception to January 2011) was performed. Articles reporting on endometrial thickness measurement in the diagnosis of endometrial carcinoma and atypical hyperplasia in asymptomatic postmenopausal women not using hormone replacement therapy (HRT) were selected. Endometrial thickness and the prevalence of endometrial (pre)malignancies were recorded. If possible, 2 × 2 tables were extracted., Results: Thirty-two studies reporting on 11100 women were included. The estimated mean endometrial thickness was 2.9 mm (95% CI, 2.6-3.3 mm). The pooled estimated prevalences of endometrial carcinoma and atypical endometrial hyperplasia were 0.62% (95% CI, 0.42-0.82%) and 0.59% (95% CI, 0.22-0.96%), respectively. Summary estimates for sensitivity and specificity of TVS endometrial thickness measurement in the prediction of endometrial carcinoma were 0.83 (95% CI, 0.19-1.00) and 0.72 (95% CI, 0.23-0.95) for a 5-mm cut-off and 0.33 (95% CI, 0.04-0.85) and 0.94 (95% CI, 0.92-0.96) for a 6-mm cut-off., Conclusions: The results from this systematic review do not justify the use of endometrial thickness as a screening test for endometrial carcinoma and atypical endometrial hyperplasia in asymptomatic postmenopausal women not using HRT., (Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.)

Background: The two most common interventions for Posttraumatic Stress Disorder (PTSD) are pharmacological treatment with SSRIs such as paroxetine and psychological treatment such as Trauma-Focused Cognitive Behavioral Therapy (TF-CBT). International guidelines recommend trauma-focused psychological interventions for all PTSD patients as first-line treatment (NICE). However, no clear-cut evidence is available to support this recommendation., Methods/design: In order to compare pharmacological treatment (paroxetine) and psychological treatment (TF-CBT) in (cost-) effectiveness on the short and the long term, we will randomize 90 patients with chronic PTSD to either paroxetine (24 weeks) or TF-CBT (10-12 weeks). We will assess symptom severity and costs before and after the intervention with the Clinician Administered PTSD Scale (CAPS), the Clinical Global Impression Scale (CGI) and the Trimbos/iMTA questionnaire for Costs associated with Psychiatric Illness (TiC-P)., Discussion: This study is unique for its direct comparison of the most commonly used psychological intervention (TF-CBT) and pharmacological intervention (paroxetine) on (cost-) effectiveness on the short and the long term. The anticipated results will provide relevant evidence concerning long-term effects and relapse rates and will be beneficial in reducing societal costs. It may also provide information on who may benefit most from which type of intervention. Some methodological issues will be discussed., Trial Registration: Dutch Trial registration: NTR2235.

Objective: The evidence for the management of near term prelabor rupture of membranes is poor. From January 2007 until September 2009, we performed the PPROM Expectant Management versus Induction of Labor (PPROMEXIL) trial. In this trial, we showed that in women with preterm prelabor rupture of membranes (PPROM), the incidence of neonatal sepsis was low, and the induction of labor (IoL) did not reduce this risk. Because the PPROMEXIL trial was underpowered and because of a lower-than-expected incidence of neonatal sepsis, we performed a second trial (PPROMEXIL-2), aiming to randomize 200 patients to improve the evidence in near-term PPROM., Study Design: In a nationwide multicenter study, nonlaboring women with PPROM between 34 and 37 weeks' gestational age were eligible for inclusion. Patients were randomized to IoL or expectant management (EM). The primary outcome measure was neonatal sepsis., Results: From December 2009 until January 2011, we randomized 100 women to IoL and 95 to EM. Neonatal sepsis was seen in 3 neonates (3.0%) in the IoL-group versus 4 neonates (4.1%) in the EM group (relative risk, 0.74; 95% confidence interval, 0.17-3.2). One of the sepsis cases in the IoL group resulted in neonatal death because of asphyxia. There were no significant differences in secondary outcomes., Conclusion: The risk of neonatal sepsis after PPROM near term is low. Induction of labor does not reduce this risk., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: Tubal patency tests are routinely performed in the diagnostic work-up of subfertile patients, but it is unknown whether these diagnostic tests add value beyond the information obtained by medical history taking and findings at physical examination. We used individual patient data meta-analysis to assess this question., Methods: We approached authors of primary studies for data sets containing information on patient characteristics and results from tubal patency tests, such as Chlamydia antibody test (CAT), hysterosalpingography (HSG) and laparoscopy. We used logistic regression to create models that predict tubal pathology from medical history and physical examination alone, as well as models in which the results of tubal patency tests are integrated in the patient characteristics model. Laparoscopy was considered to be the reference test., Results: We obtained data from four studies reporting on 4883 women. The duration of subfertility, number of previous pregnancies and a history of previous pelvic inflammatory disease (PID), pelvic surgery or Chlamydia infection qualified for the patient characteristics model. This model showed an area under the receiver operating characteristic curve (AUC) of 0.63 [95% confidence interval (CI) 0.61-0.65]. For any tubal pathology, the addition of HSG significantly improved the predictive performance to an AUC of 0.74 (95% CI 0.73-0.76) (P < 0.001). For bilateral tubal pathology, the addition of both CAT and HSG increased the predictive performance to an AUC of 0.76 (95% CI 0.74-0.79)., Conclusions: In the work-up for subfertile couples, the combination of patient characteristics with CAT and HSG results gives the best diagnostic performance for the diagnosis of bilateral tubal pathology.

Objectives: To develop prediction models for long-term respiratory morbidity. To explore if respiratory distress syndrome (RDS) is a risk-indicator for long-term respiratory morbidity and to identify other perinatal risk-indicators for long-term respiratory morbidity., Study Design: In the Dutch POPS cohort 1338 live born infants delivered in The Netherlands in 1983, either before 32 completed weeks gestation and/or with a birth weight below 1500 g, were followed prospectively. We used multivariable logistic regression analyses to construct three prediction models for respiratory morbidity at 2, 5 and 19 years of age., Results: At 2 years of age, maternal smoking (adjusted OR 1.5, 95% CI 1.0-2.4), prolonged rupture of membranes (adjusted OR 2.3, 95% CI 1.3-4.1), pre-eclampsia (adjusted OR 1.9, 95% CI 1.1-4.1), male gender (adjusted OR 1.5, 95% CI 1.1-2.0) and BPD (adjusted OR 1.9, 95% CI 1.1-3.2) were significantly associated with respiratory morbidity. Prolonged rupture of membranes (adjusted OR 3.7, 95% CI 1.6-8.5), family history of asthma (adjusted OR 5.9, 95% CI 2.7-13.0) and BPD (adjusted OR 1.8, 95% CI 1.1-3.0) were significantly associated with respiratory morbidity at 5 years of age. At 19 years of age only higher social class was associated with decreased respiratory morbidity (adjusted OR 0.64, 95% CI 0.41-0.99). The areas under the curves (AUC) were 0.65, 0.71 and 0.61 respectively. The prediction models for respiratory morbidity at 2 and 5 years of age showed a good calibration, while the calibration plot for respiratory morbidity at 19 year was less optimal., Conclusions: RDS is not a risk-indicator for long-term respiratory morbidity at 2, 5 and 19 years in this cohort (OR 1.2, 95% 0.88-1.7; 1.3, 95% 0.88-2.0; OR 0.91, 95% 0.56-1.5 respectively). Future obstetric studies interested in the effect of a specific perinatal intervention on long-term respiratory morbidity, should consider taking bronchopulmonary dysplasia (BPD) as primary outcome instead of RDS., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Empirical data have challenged the unidimensionality of the Peritraumatic Dissociative Experiences Questionnaire (PDEQ), a widely used measure for peritraumatic dissociation. The aim of this study was to assess the factor structure of the PDEQ in 3 trauma-exposed samples: (a) trauma-exposed police officers (N = 219); (b) trauma-exposed civilians (N = 158); and (c) treatment-seeking trauma-exposed civilians (N = 185). Confirmatory factor analyses using measurement invariance testing supported a 2-factor structure (CFIs .96-.98; RMSEAs .07-.09), but excluded 2 of the original items. Factor 1 was termed Altered Awareness; Factor 2 was termed Derealization. Altered Awareness reflected disturbances in information processing during the traumatic event, whereas Derealization reflected distortions in perception. Hierarchical linear regression analysis showed that Derealization predicted posttraumatic stress severity at 26.5 weeks follow-up only in the sample of police officers (R(2) = .45). Future longitudinal research shortly following trauma is required to elucidate causality and underlying mechanisms of peritraumatic dissociation, which may contribute to the development of more accurate screening strategies, as well as more effective strategies for prevention and early intervention., (Copyright © 2012 International Society for Traumatic Stress Studies.)

Objective: To evaluate the cost-effectiveness of diagnostic strategies incorporating the diagnostic value of patient characteristics for endometrial carcinoma using prediction models., Study Design: A decision analytic model was created to compare four diagnostic strategies for women with postmenopausal bleeding: the main outcome measures were 5 year survival, costs, and cost-effectiveness of three model based strategies compared to the strategy reflecting current practice., Results: A strategy selecting women for endometrial biopsy based on their history only, dominated all other strategies (more effective, less cost). In a clinical scenario where transvaginal sonography (TVS) was assumed to be an integral part of the consultation without additional costs, a strategy selecting high-risk women for TVS became the most cost-effective strategy., Conclusions: Strategies taking into account the individual probability based on a prognostic model are less costly than the currently applied strategy for a similar effectiveness. The most cost-effective strategy depends on the clinical setting: in areas where TVS is performed by the consulting gynecologist without extra costs, selective TVS based on history is the most cost-effective strategy. When TVS is not readily available and therefore incurs extra costs, a risk selection based on patient characteristics is most cost-effective., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: We performed a systematic review to determine whether sonographic assessment of occipital position of the fetal head can contribute to the prediction of the mode of delivery., Methods: We performed a systematic literature search of electronic databases from inception to May 2011. Two reviewers independently extracted data from the included studies. We used a bivariate model to estimate point estimates for sensitivity and specificity curves for the outcome Cesarean delivery. Eligible studies were cohort studies or cross-sectional studies that reported on both the position of the fetal head, as assessed by ultrasound, before or at the beginning of active labor as well as the outcome of labor in women at term., Results: We included 11 primary articles reporting on 5053 women, of whom 898 had a Cesarean section. All studies indicated disappointing values for sensitivity and specificity in the prediction of Cesarean section. Summary point estimates of sensitivity and specificity were 0.39 (95% CI, 0.32-0.48) and 0.71 (95% CI, 0.67-0.74), respectively., Conclusion: Sonographic assessment of occipital position of the fetal head before delivery should not be used in the prediction of mode of delivery., (Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.)

Research into the diagnostic accuracy of clinical tests is often hampered by single or double partial verification mechanisms, that is, not all patients have their disease status verified by a reference test, neither do all patients receive all tests under evaluation (index tests). We show methods that reduce verification bias introduced when omitting data from partially tested patients. Adjustment techniques are well established when there are no missing index tests and when the reference test is 'missing at random'. However, in practice, index tests tend to be omitted, and the choice of applying a reference test may depend on unobserved variables related to disease status, that is, verification may be missing not at random (MNAR). We study double partial verification in a clinical example from reproductive medicine in which we analyse the diagnostic values of the chlamydia antibody test and the hysterosalpingography in relation to a diagnostic laparoscopy. First, we plot all possible combinations of sensitivity and specificity of both index tests in two test ignorance regions. Then, we construct models in which we impose different assumptions for the verification process. We allow for missing index tests, study the influence of patient characteristics and study the accuracy estimates if an MNAR mechanism would operate. It is shown that data on tests used in the diagnostic process of the same population are preferably studied jointly and that the influence of an MNAR verification process was limited in a clinical study where more than half of the patients did not have the reference test., (Copyright © 2011 John Wiley & Sons, Ltd.)