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Background: One of the most commonly reported problems of randomised trials is that recruitment is usually slower than expected. Trials will cost more and take longer, thus delaying the use of the results in clinical practice, and incomplete samples imply decreased statistical power and usefulness of its results. We aim to identify barriers and facilitators for successful patient recruitment at the level of the patient, the doctor and the hospital organization as well as the organization and design of trials over a broad range of studies.Methods/design: We will perform two cohort studies and a case-control study in The Netherlands. The first cohort study will report on a series of multicenter trials performed in a nationwide network of clinical trials in obstetrics and gynaecology. A questionnaire will be sent to all clinicians recruiting for these trials to identify determinants--aggregated at centre level--for the recruitment rate. In a case control-study nested in this cohort we will interview patients who refused or consented participation to identify factors associated with patients' consent or refusal. In a second cohort study, we will study trials that were prospectively registered in the Netherlands Trial Register. Using a questionnaire survey we will assess whether issues on hospital organization, trial organization, planning and trial design were associated with successful recruitment, i.e. 80% of the predefined number of patients recruited within the planned time.Discussion: This study will provide insight in barriers and facilitators for successful patient recruitment in trials. The results will be used to provide recommendations and a checklist for individual trialists to identify potential pitfalls for recruitment and judge the feasibility prior to the start of the study. Identified barriers and motivators coupled to evidence-based interventions can improve recruitment of patients in clinical trials. [ABSTRACT FROM AUTHOR]

Background: Preterm labour is the main cause of perinatal morbidity and mortality in the Western world. At present, there is evidence that tocolysis for 48 hours is useful in women with threatened preterm labour at least before 32 weeks. This allows transfer of the patient to a perinatal centre, and maximizes the effect of corticosteroids for improved neonatal survival. It is questionable whether treatment with tocolytics should be maintained after 48 hours.Methods/design: The APOSTEL II trial is a multicentre placebo-controlled study. Pregnant women admitted for threatened preterm labour who have been treated with 48 hours corticosteroids and tocolysis will be eligible to participate in the trial between 26+0 and 32+2 weeks gestational age. They will be randomly allocated to nifedipine (intervention) or placebo (control) for twelve days or until delivery, whatever comes first.Primary outcome is a composite of perinatal death, and severe neonatal morbidity up to evaluation at 6 months after birth. Secondary outcomes are gestational age at delivery, number of days in neonatal intensive care and total days of the first 6 months out of hospital. In addition a cost-effectiveness analysis will be performed. Analysis will be by intention to treat. The power calculation is based on an expected 11% difference in adverse neonatal outcome. This implies that 406 women have to be randomised (two sided test, beta 0.2 at alpha 0.05).Discussion: This trial will provide evidence as to whether maintenance tocolysis reduces severe perinatal morbidity and mortality in women with threatened preterm labour before 32 weeks.Trial Registration: Clinical Trial Registration: http://www.trialregister.nl, NTR 1336, date of registration: June 3rd 2008. [ABSTRACT FROM AUTHOR]

Background: At present, women with threatened preterm labor before 32 weeks of gestation are, after transfer to a perinatal center, treated with tocolytics and corticosteroids. Many of these women are treated unnecessarily. Fibronectin is an accurate predictor for the occurrence of preterm birth among women with threatened preterm labor. We will assess whether triage of these women with fibronectin testing, cervical length or their combination is cost-effective.Methods/design: We will investigate a prospective cohort of women referred to a perinatal centre for spontaneous threatened preterm labor between 24 and 34 weeks with intact membranes. All women will be tested for fibronectin and cervical length. Women with a cervical length <10 mm and women with a cervical length between 10-30 mm in combination with a positive fibronectin test will be treated with tocolytics according to local protocol. Women with a cervical length between 10-30 mm in combination with a negative fibronectin test will be randomised between treatment with nifedipine (intervention) and placebo (control) for 48 hours. Women with a cervical length > 30 mm will be managed according to local protocol. Corticosteroids may be given to all women at the discretion of the attending physician. Primary outcome measure will be delivery within 7 days. Secondary outcome measures will be neonatal morbidity and mortality, complications of tocolytics, costs and health related quality of life. The analysis will be according to the intention to treat principle. We anticipate the probability on preterm birth within 7 days in the group of women with a negative fibronectine test to be 5%. Two groups of 110 women will be needed to assure that in case of non-inferiority the difference in the proportion of preterm deliveries < 7 days will be within a prespecified boundary of 7.5% (one sided test, beta 0.2, alpha 0.05). Data obtained from women with a positive and negative fibronectin tests in both the cohort study and the trial will be integrated in a cost-effectiveness analysis that will assess economic consequences of the use of fibronectin.Discussion: This study will provide evidence for the use of fibronectin testing as safe and cost-effective method in a triage for threatened preterm labor.Trial Registration: Nederlands Trial Register (NTR) number 1857, http://www.trialregister.nl. [ABSTRACT FROM AUTHOR]

Background: Urinary and (peripheral and central) intravenous catheters are widely used in hospitalized patients. However, up to 56% of the catheters do not have an appropriate indication and some serious complications with the use of these catheters can occur. The main objective of our quality improvement project is to reduce the use of catheters without an appropriate indication by 25-50%, and to evaluate the affecting factors of our de-implementation strategy., Methods: In a multicenter, prospective interrupted time series analysis, several interventions to avoid inappropriate use of catheters will be conducted in seven hospitals in the Netherlands. Firstly, we will define a list of appropriate indications for urinary and (peripheral and central) intravenous catheters, which will restrict the use of catheters and urge catheter removal when the indication is no longer appropriate. Secondly, after the baseline measurements, the intervention will take place, which consists of a kick-off meeting, including a competitive feedback report of the baseline measurements, and education of healthcare workers and patients. Additional strategies based on the baseline data and local conditions are optional. The primary endpoint is the percentage of catheters with an inappropriate indication on the day of data collection before and after the de-implementation strategy. Secondary endpoints are catheter-related infections or other complications, catheter re-insertion rate, length of hospital (and ICU) stay and mortality. In addition, the cost-effectiveness of the de-implementation strategy will be calculated., Discussion: This study aims to reduce the use of urinary and intravenous catheters with an inappropriate indication, and as a result reduce the catheter-related complications. If (cost-) effective it provides a tool for a nationwide approach to reduce catheter-related infections and other complications., Trial Registration: Dutch trial registry: NTR6015 . Registered 9 August 2016.

Background: Preterm birth is a major cause of neonatal mortality and morbidity. As preventive strategies are largely ineffective, threatened preterm labor is a frequent problem that affects approximately 10 % of pregnancies. In recent years, risk assessment in these women has incorporated cervical length measurement and fetal fibronectin testing, and this has improved the capacity to identify women at increased risk for delivery within 14 days. Despite these improvements, risk for preterm birth continues to be increased in women who did not deliver after an episode of threatened preterm labor, as indicated by a preterm birth rate between 30 to 60 % in this group of women. Currently no effective treatment is available. Studies on maintenance tocolysis and progesterone have shown ambiguous results. The pessary has not been evaluated in women with threatened preterm labor, however studies in asymptomatic women with a short cervix show reduced rates of preterm birth rates as well as perinatal complications. The APOSTEL VI trial aims to assess the effectiveness of a cervical pessary in women who did not deliver within 48 h after an episode of threatened preterm labor., Methods/design: This is a nationwide multicenter open-label randomized clinical trial. Women with a singleton or twin gestation with intact membranes, who were admitted for threatened preterm labor, at a gestational age between 24 and 34 weeks, a cervical length between 15 and 30 mm and a positive fibronectin test or a cervical length below 15 mm, who did not deliver after 48 h will be eligible for inclusion. Women will be allocated to a pessary or no intervention (usual care). Primary outcome is preterm delivery < 37 weeks. Secondary outcomes are amongst others a composite of perinatal morbidity and mortality. Sample size is based on an expected 50 % reduction of preterm birth before 37 weeks (two-sided test, α 0.05 and β 0.2). Two hundred women with a singleton pregnancy need to be randomized. Analysis will be done by intention to treat., Discussion: The APOSTEL VI trial will provide evidence whether a pessary is effective in preventing preterm birth in women who did not deliver 48 h after admission for threatened preterm labor and who remain at high risk for preterm birth., Trial Registration: Trial is registered at the Dutch Trial Register: http://www.trialregister.nl , NTR4210, date of registration: October 16th 2013.

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.

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.

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).

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.

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.

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.

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.

Background: Standard treatment of advanced ovarian cancer is surgery and chemotherapy. The goal of surgery is to remove all macroscopic tumour, as the amount of residual tumour is the most important prognostic factor for survival. When removal off all tumour is considered not feasible, neoadjuvant chemotherapy (NACT) in combination with interval debulking surgery (IDS) is performed. Current methods of staging are not always accurate in predicting surgical outcome, since approximately 40% of patients will have more than 1 cm residual tumour after primary debulking surgery (PDS). In this study we aim to assess whether adding laparoscopy to the diagnostic work-up of patients suspected of advanced ovarian carcinoma may prevent unsuccessful primary debulking surgery for ovarian cancer., Methods: Multicentre randomized controlled trial, including all gynaecologic oncologic centres in the Netherlands and their affiliated hospitals. Patients are eligible when they are planned for PDS after conventional staging. Participants are randomized between direct PDS or additional diagnostic laparoscopy. Depending on the result of laparoscopy patients are treated by PDS within three weeks, followed by six courses of platinum based chemotherapy or with NACT and IDS 3-4 weeks after three courses of chemotherapy, followed by another three courses of chemotherapy. Primary outcome measure is the proportion of PDS's leaving more than one centimetre tumour residual in each arm. In total 200 patients will be randomized. Data will be analysed according to intention to treat., Discussion: Patients who have disease considered to be resectable to less than one centimetre should undergo PDS to improve prognosis. However, there is a need for better diagnostic procedures because the current number of debulking surgeries leaving more than one centimetre residual tumour is still high. Laparoscopy before starting treatment for ovarian cancer can be an additional diagnostic tool to predict the outcome of PDS. Despite the absence of strong evidence and despite the possible complications, laparoscopy is already implemented in many countries. We propose a randomized multicentre trial to provide evidence on the effectiveness of laparoscopy before primary surgery for advanced stage ovarian cancer patients., Trial Registration: Netherlands Trial Register number NTR2644.

Background: Many perinatal interventions are performed to improve long-term neonatal outcome. To evaluate the long-term effect of a perinatal intervention follow-up of the child after discharge from the hospital is necessary because serious sequelae from perinatal complications frequently manifest themselves only after several years. However, long-term follow-up is time-consuming, is not in the awareness of obstetricians, is expensive and falls outside the funding-period of most obstetric studies. Consequently, short-term outcomes are often reported instead of the primary long-term end-point. With this project, we will assess the current state of affairs concerning follow-up after obstetric RCTs and we will develop multivariable prediction models for different long-term health outcomes. Furthermore, we would like to encourage other researchers participating in follow-up studies after large obstetric trials (> 350 women) to inform us about their studies so that we can include their follow-up study in our systematic review. We would invite these researchers also to join our effort and to collaborate with us on the external validation of our prediction models., Methods/design: A systematic review of neonatal follow-up after obstetric studies will be performed. All reviews of the Cochrane Pregnancy and Childbirth group will be assessed for reviews on interventions that aimed to improve neonatal outcome. Reviews on interventions primary looking at other aspects than neonatal outcome such as labour progress will also be included when these interventions can change the outcome of the neonate on the short or long-term. Our review will be limited to RCTs with more than 350 women. Information that will be extracted from these RCTs will address whether, how and for how long follow-up has been performed. However, in many cases long-term follow-up of the infants will not be feasible. An alternative solution to limited follow-up could be to develop prediction models to estimate long-term health outcomes of the newborn based on specific perinatal outcomes and other covariates. For the development of multivariable prediction models for several health outcomes, we will use data available from a Dutch cohort study of preterm (< 32 weeks) and/or small for gestational age infants (< 1500 g). These infants were born in The Netherlands in 1983 and followed until they reached the age of 19., Discussion: The systematic review will provide insight in the extent and methods used for follow-up assessments after obstetric RCTs in the past. The prediction models can be used by future studies to extrapolate short-term outcomes to a long-term horizon or to indicate for which neonates long-term follow-up is required, as their outcomes (either absence or presence of sequelae) cannot be adequately predicted from short-term outcomes and clinical background characteristics.

Background: Breech presentation occurs in 3 to 4% of all term pregnancies. External cephalic version (ECV) is proven effective to prevent vaginal breech deliveries and therefore it is recommended by clinical guidelines of the Royal Dutch Organisation for Midwives (KNOV) and the Dutch Society for Obstetrics and Gynaecology (NVOG). Implementation of ECV does not exceed 50 to 60% and probably less.We aim to improve the implementation of ECV to decrease maternal and neonatal morbidity and mortality due to breech presentations. This will be done by defining barriers and facilitators of implementation of ECV in the Netherlands. An innovative implementation strategy will be developed based on improved patient counselling and thorough instructions of health care providers for counselling., Method/design: The ultimate purpose of this implementation study is to improve counselling of pregnant women and information of clinicians to realize a better implementation of ECV.The first phase of the project is to detect the barriers and facilitators of ECV. The next step is to develop an implementation strategy to inform and counsel pregnant women with a breech presentation, and to inform and educate care providers. In the third phase, the effectiveness of the developed implementation strategy will be evaluated in a randomised trial. The study population is a random selection of midwives and gynaecologists from 60 to 100 hospitals and practices. Primary endpoints are number of counselled women. Secondary endpoints are process indicators, the amount of fetes in cephalic presentation at birth, complications due to ECV, the number of caesarean sections and perinatal condition of mother and child. Cost effectiveness of the implementation strategy will be measured., Discussion: This study will provide evidence for the cost effectiveness of a structural implementation of external cephalic versions to reduce the number of breech presentations at term., Trial Registration: Dutch Trial Register (NTR): 1878.

Background: In clinical practice a diagnosis is based on a combination of clinical history, physical examination and additional diagnostic tests. At present, studies on diagnostic research often report the accuracy of tests without taking into account the information already known from history and examination. Due to this lack of information, together with variations in design and quality of studies, conventional meta-analyses based on these studies will not show the accuracy of the tests in real practice. By using individual patient data (IPD) to perform meta-analyses, the accuracy of tests can be assessed in relation to other patient characteristics and allows the development or evaluation of diagnostic algorithms for individual patients. In this study we will examine these potential benefits in four clinical diagnostic problems in the field of gynaecology, obstetrics and reproductive medicine., Methods/design: Based on earlier systematic reviews for each of the four clinical problems, studies are considered for inclusion. The first authors of the included studies will be invited to participate and share their original data. After assessment of validity and completeness the acquired datasets are merged. Based on these data, a series of analyses will be performed, including a systematic comparison of the results of the IPD meta-analysis with those of a conventional meta-analysis, development of multivariable models for clinical history alone and for the combination of history, physical examination and relevant diagnostic tests and development of clinical prediction rules for the individual patients. These will be made accessible for clinicians., Discussion: The use of IPD meta-analysis will allow evaluating accuracy of diagnostic tests in relation to other relevant information. Ultimately, this could increase the efficiency of the diagnostic work-up, e.g. by reducing the need for invasive tests and/or improving the accuracy of the diagnostic workup. This study will assess whether these benefits of IPD meta-analysis over conventional meta-analysis can be exploited and will provide a framework for future IPD meta-analyses in diagnostic and prognostic research.

Background: Preterm prelabour rupture of the membranes (PPROM) is an important clinical problem and a dilemma for the gynaecologist. On the one hand, awaiting spontaneous labour increases the probability of infectious disease for both mother and child, whereas on the other hand induction of labour leads to preterm birth with an increase in neonatal morbidity (e.g., respiratory distress syndrome (RDS)) and a possible rise in the number of instrumental deliveries., Methods/design: We aim to determine the effectiveness and cost-effectiveness of immediate delivery after PPROM in near term gestation compared to expectant management. Pregnant women with preterm prelabour rupture of the membranes at a gestational age from 34+0 weeks until 37+0 weeks will be included in a multicentre prospective randomised controlled trial. We will compare early delivery with expectant monitoring. The primary outcome of this study is neonatal sepsis. Secondary outcome measures are maternal morbidity (chorioamnionitis, puerperal sepsis) and neonatal disease, instrumental delivery rate, maternal quality of life, maternal preferences and costs. We anticipate that a reduction of neonatal infection from 7.5% to 2.5% after induction will outweigh an increase in RDS and additional costs due to admission of the child due to prematurity. Under these assumptions, we aim to randomly allocate 520 women to two groups of 260 women each. Analysis will be by intention to treat. Additionally a cost-effectiveness analysis will be performed to evaluate if the cost related to early delivery will outweigh those of expectant management. Long term outcomes will be evaluated using modelling., Discussion: This trial will provide evidence as to whether induction of labour after preterm prelabour rupture of membranes is an effective and cost-effective strategy to reduce the risk of neonatal sepsis. CONTROLLED CLINICAL TRIAL REGISTER: ISRCTN29313500.

Background: To compare health related quality of life (HR-QoL) in patients surgically treated for secondary peritonitis to that of a healthy population. And to prospectively identify factors associated with poorer (lower) HR-QoL., Design: A prospective cohort of secondary peritonitis patients was mailed the EQ-5D and EQ-VAS 6-months following initial laparotomy., Setting: Multicenter study in two academic and seven regional teaching hospitals., Patients: 130 of the 155 eligible patients (84%) responded to the HR-QoL questionnaires., Results: HR-QoL was significantly worse on all dimensions in peritonitis patients than in a healthy reference population. Peritonitis characteristics at initial presentation were not associated with HR-QoL at six months. A more complicated course of the disease leading to longer hospitalization times and patients with an enterostomy had a negative impact on the mobility (p = 0.02), self-care (p < 0.001) and daily activities: (p = 0.01). In a multivariate analysis for the EQ-VAS every doubling of hospital stay decreases the EQ-VAS by 3.8 points (p = 0.015). Morbidity during the six-month follow-up was not found to be predictive for the EQ-5D or EQ-VAS., Conclusion: Six months following initial surgery, patients with secondary peritonitis report more problems in HR-QoL than a healthy reference population. Unfavorable disease characteristics at initial presentation were not predictive for poorer HR-QoL, but a more complicated course of the disease was most predictive of HR-QoL at 6 months.