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Objective: To compare two quality improvement (QI) interventions to improve antenatal magnesium sulphate (MgSO 4 ) uptake in preterm births for the prevention of cerebral palsy., Design: Unblinded cluster randomised controlled trial., Setting: Academic Health Sciences Network, England, 2018., Sample: Maternity units with ≥10 preterm deliveries annually and MgSO 4 uptake of ≤70%; 40 (27 NPP, 13 enhanced support) were included (randomisation stratified by MgSO 4 uptake)., Methods: The National PReCePT Programme (NPP) gave maternity units QI materials (clinical guidance, training), regional support, and midwife backfill funding. Enhanced support units received this plus extra backfill funding and unit-level QI coaching., Main Outcome Measures: MgSO 4 uptake was compared using routine data and multivariable linear regression. Net monetary benefit was estimated, based on implementation costs, lifetime quality-adjusted life-years and societal costs. The implementation process was assessed through qualitative interviews., Results: MgSO 4 uptake increased in all units, with no evidence of any difference between groups (0.84 percentage points lower uptake in the enhanced group, 95% CI -5.03 to 3.35). The probability of enhanced support being cost-effective was <30%. NPP midwives gave more than their funded hours for implementation. Units varied in their support needs. Enhanced support units reported better understanding, engagement and perinatal teamwork., Conclusions: PReCePT improved MgSO 4 uptake in all maternity units. Enhanced support did not further improve uptake but may improve teamwork, and more accurately represented the time needed for implementation. Targeted enhanced support, sustainability of improvements and the possible indirect benefits of stronger teamwork associated with enhanced support should be explored further., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Background: Various metrics of hospital antibiotic use might assist in guiding antimicrobial stewardship (AMS)., Objectives: To compare patient outcomes in association with three methods to measure and feedback information on hospital antibiotic use when used in developing an AMS intervention., Methods: Three methods were randomly allocated to 42 clusters from 21 Dutch hospitals: (1) feedback on quantity of antibiotic use [DDD, days-of-therapy (DOT) from hospital pharmacy data], versus feedback on (2) validated, or (3) non-validated quality indicators from point prevalence studies. Using this feedback together with an implementation tool, stewardship teams systematically developed and performed improvement strategies. The hospital length of stay (LOS) was the primary outcome and secondary outcomes included DOT, ICU stay and hospital mortality. Data were collected before (February-May 2015) and after (February-May 2017) the intervention period., Results: The geometric mean hospital LOS decreased from 9.5 days (95% CI 8.9-10.1, 4245 patients) at baseline to 9.0 days (95% CI 8.5-9.6, 4195 patients) after intervention (P < 0.001). No differences in effect on LOS or secondary outcomes were found between methods. Feedback on quality of antibiotic use was used more often to identify improvement targets and was preferred over feedback on quantity of use. Consistent use of the implementation tool seemed to increase effectiveness of the AMS intervention., Conclusions: The decrease in LOS versus baseline likely reflects improvement in the quality of antibiotic use with the stewardship intervention. While the outcomes with the three methods were otherwise similar, stewardship teams preferred data on the quality over the quantity of antibiotic use., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Background: Catheter-associated bloodstream infections and urinary tract infections are frequently encountered health care-associated infections. We aimed to reduce inappropriate use of catheters to reduce health care-associated infections., Methods: In this multicentre, interrupted time-series and before and after study, we introduced a de-implementation strategy with multifaceted interventions in seven hospitals in the Netherlands. Adult patients admitted to internal medicine, gastroenterology, geriatic, oncology, or pulmonology wards, and non-surgical acute admission units, and who had a (central or peripheral) venous or urinary catheter were eligible for inclusion. One of the interventions was that nurses in the participating wards attended educational meetings on appropriate catheter use. Data on catheter use were collected every 2 weeks by the primary research physician during the baseline period (7 months) and intervention period (7 months), which were separated by a 5 month transition period. The primary outcomes were percentages of short peripheral intravenous catheters and urinary catheters used inappropriately on the days of data collection. Indications for catheter use were based on international guidelines. This study is registered with Netherlands Trial Register, NL5438., Findings: Between Sept 1, 2016, and April 1, 2018, we screened 6157 patients for inclusion, of whom 5696 were enrolled: 2650 patients in the baseline group, and 3046 in the intervention group. Inappropriate use of peripheral intravenous catheters occurred in 366 (22·0%, 95% CI 20·0 to 24·0) of 1665 patients in the baseline group and in 275 (14·4%, 12·8 to 16·0) of 1912 patients in the intervention group (incidence rate ratio [IRR] 0·65, 95% CI 0·56 to 0·77, p<0·0001). Time-series analyses showed an absolute reduction in inappropriate use of peripheral intravenous catheters from baseline to intervention periods of 6·65% (95% CI 2·47 to 10·82, p=0·011). Inappropriate use of urinary catheters occurred in 105 (32·4%, 95% CI 27·3 to 37·8) of 324 patients in the baseline group compared with 96 (24·1%, 20·0 to 28·6) of 398 patients in the intervention group (IRR 0·74, 95% CI 0·56 to 0·98, p=0·013). Time-series analyses showed an absolute reduction in inappropriate use of urinary catheters of 6·34% (95% CI -12·46 to 25·13, p=0·524)., Interpretation: Our de-implementation strategy reduced inappropriate use of short peripheral intravenous catheters in patients who were not in the intensive care unit. The reduction of inappropriate use of urinary catheters was substantial, yet not statistically significant in time-series analysis due to a small sample size. The strategy appears well suited for broad-scale implementation to reduce health care-associated infections., Funding: Netherlands Organisation for Health Research and Development., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: To investigate whether antibiotic treatment of 6 days' duration is non-inferior to treatment for 12 days in patients hospitalized for cellulitis., Methods: This multicentre, randomized, double-blind, placebo-controlled, non-inferiority trial enrolled adult patients hospitalized for severe cellulitis who were treated with intravenous flucloxacillin. At day 6 participants with symptom improvement who were afebrile were randomized between an additional 6 days of oral flucloxacillin or placebo in a 1:1 ratio, stratified for diabetes and hospital. The primary outcome was cure by day 14, without relapse by day 28. Secondary outcomes included a modified cure assessment and relapse rate by day 90., Results: Between August 2014 and June 2017, 151 of 248 included participants were randomized. The intention-to-treat population consisted of 76 and 73 participants allocated to 12 and 6 days of antibiotic therapy, respectively (mean age 62 years, 67% males, 24% diabetics); 38/76 (50.0%) and 36/73 (49.3%) were cured in the 12- and 6-day groups respectively (ARR 0.7 percentage points, 95%CI: -15.0 to 16.3). Cure rates were 56/76 (73.7%) and 49/73 (67.1%) with the modified cure assessment (ARR 6.6, 95%CI: -8.0 to 20.8). After initial cure without relapse, day 90 relapse rates were higher in the 6-day group (6% versus 24%, p < 0.05)., Conclusions: Given the wide confidence intervals, we can neither confirm nor refute our hypothesis that 6 days of therapy is non-inferior to 12 days of therapy. However, a 6-day course resulted in significantly more frequent relapses by day 90. These findings require confirmation in future studies., (Copyright © 2019. Published by Elsevier Ltd.)

Introduction: The ProTWIN trial previously showed no beneficial effect of treatment with a cervical pessary vs usual care to prevent preterm birth in women with a multiple pregnancy. However, in women with a midtrimester short cervix (<38 mm), pessary did reduce the composite outcome of neonatal morbidity and mortality. This follow-up study evaluates the long-term outcomes of all children born to mothers who participated in the ProTWIN trial at 4 years of age., Material and Methods: Parents received the Ages and Stages Questionnaire, Strength and Difficulties Questionnaire and a health questionnaire. All questionnaires were reported separately and as a combined outcome (abnormal child outcome). A linear mixed effects model was used to adjust for correlated data in twins and correction for confounders was performed. In exploratory analysis, a composite outcome of death or survival with abnormal child outcome was used by combining extrapolated data on child outcome with survival data. All data were analyzed for the total group and the subgroup of women with midtrimester short cervix., Results: Of the original 813 women of the ProTWIN trial, we approached 579, of whom 258 participated (45%) in follow-up. We received questionnaires of 514 children (281 pessary vs 233 control), with 119 children in the subgroup of women with midtrimester short cervix. An abnormal child outcome was found in 23% in the pessary group vs 16% in the control group (odds ratio 1.58; 95% confidence interval 0.94-2.65). In exploratory analysis with extrapolated data on child outcome (n = 815), no difference in abnormal child outcome was seen between the pessary and control group. In the subgroup of women with a short cervix (n = 268), this composite outcome indicated a favorable outcome for children born to mothers with pessary., Conclusions: In women with a multiple pregnancy, the use of a cervical pessary did not improve development, behavior or physical outcomes of the surviving children at age 4., (© 2019 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Introduction and Hypothesis: There is increased demand for an international overview of cost estimates and insight into the variation affecting these estimates. Understanding of these costs is useful for cost-effectiveness analysis (CEA) research into new treatment modalities and for clinical guideline development., Methods: A systematic search was conducted in Ovid MEDLINE & other non-indexed materials and Ovid Embase for articles published between 1995 and 2017. The National Health Service Economic Evaluation Database (NHS-EED) filter and the McMaster sensitive therapy filter were combined with a bespoke search strategy for stress urinary incontinence (SUI). We extracted unit cost estimates, assessed variability and methodology, and determined transferability., Results: We included 37 studies in this review. Four hundred and eighty-two cost estimates from 13 countries worldwide were extracted. Descriptive analysis shows that hospital stay in gynecology ranged between €82 and €1,292 per day. Costs of gynecological consultation range from €30 in France to €158 in Sweden. In the UK, costs are estimated at €228 per hour. Costs of a tension-free vaginal tape (TVT) device range from €431 in Finland to €994 in Canada. TVT surgery per minute costs €25 in France and €82 in Sweden. Total costs of TVT range from €1,224 in Ireland to €5,809 for inpatient care in France. Variation was explored., Conclusions: Heterogeneity was observed in cost estimates for all units at all levels of health care. CEAs of SUI interventions cannot be interpreted without bias when the base of these analyses-namely costs-cannot be compared and generalized.

A cornerstone of antimicrobial stewardship programs (ASPs) is monitoring quantitative antibiotic use. Frequently used metrics are defined daily dose (DDD) and days of therapy (DOT). The purpose of this study was (1) to explore for the hospital setting the possibilities of quantitative data retrieval on the level of medical specialty and (2) to describe factors affecting the usability and interpretation of these quantitative metrics. We performed a retrospective observational study, measuring overall systemic antibiotic use at specialty level over a 1-year period, from December 1st 2014 to December 1st 2015, in one university and 13 non-university hospitals in the Netherlands. We distinguished surgical and non-surgical adult specialties. The association between DDDs, calculated from aggregated dispensing data, and DOTs, calculated from patient-level prescription data, was explored descriptively and related to organizational factors, data sources (prescription versus dispensing data), data registration, and data extraction. Twelve hospitals were able to extract dispensing data (DDD), three of which on the level of medical specialty; 13 hospitals were able to extract prescription data (DOT), 11 of which by medical specialty. A large variation in quantitative antibiotic use was found between hospitals and the correlation between DDDs and DOTs at specialty level was low. Differences between hospitals related to organizational factors, data sources, data registration, and data extraction procedures likely contributed to the variation in quantitative use and the low correlation between DDDs and DOTs. The differences in healthcare organization, data sources, data registration, and data extraction procedures contributed to the variation in reported quantitative use between hospitals. Uniform registration and extraction procedures are necessary for appropriate measurement and interpretation and benchmarking of quantitative antibiotic use.

Objective: A recent randomized clinical trial (ProTWIN) showed that a cervical pessary prevented preterm birth and improved neonatal outcome in women with multiple pregnancy and cervical length (CL) < 38 mm. In this follow-up study, the long-term developmental outcome of these children was evaluated at 3 years' corrected age., Methods: This was a follow-up study of ProTWIN, a multicenter trial conducted between 2009 and 2012 in which asymptomatic women with a multiple pregnancy were randomized to placement of a cervical pessary or no intervention. Current follow-up and analysis were limited to mothers with a mid-trimester CL < 38 mm (78 women (157 children) in the pessary group and 55 women (111 children) in the control group). At 3 years of corrected age, surviving children were invited for a Bayley Scales of Infant and Toddler Development-third edition (Bayley-III) assessment. Death after randomization or neurodevelopmental disability (Bayley-III score of ≤ 85, 1 SD below mean) rates were compared between the pessary and control groups, according to the intention-to-treat principle and using multiple imputation for missing data. Mean Bayley-III scores in surviving children were also assessed. A linear mixed-effects model was used to adjust for correlation between children of one mother., Results: From the time of entry in the ProTWIN trial until follow-up at 3 years of age, a total of 27 children had died (six (5%) in the pessary vs 21 (26%) in the control group; odds ratio (OR), 0.13; 95% CI, 0.04-0.48). Bayley-III outcomes were collected for 173/241 (72%) surviving children (114 (75%) in the pessary vs 59 (66%) in the control group). The cumulative incidence of death or survival with a neurodevelopmental disability was 12 (10%) in the pessary vs 23 (29%) in the control group (OR, 0.26; 95% CI, 0.09-0.73). No statistical or clinically relevant differences were found with respect to cognitive, language and motor development among surviving children between the groups. Comparable results were found after multiple imputation., Conclusion: In women with twin pregnancy and a CL < 38 mm, the use of a cervical pessary strongly improved survival of the children without affecting neurodevelopment at 3 years' corrected age. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To evaluate the cost-effectiveness of combining cervical-length (CL) measurement and fetal fibronectin (fFN) testing in women with symptoms of preterm labor between 24 and 34 weeks' gestation., Methods: This was a model-based cost-effectiveness analysis evaluating seven test-treatment strategies based on CL measurement and/or fFN testing in women with symptoms of preterm labor from a societal perspective, in which neonatal outcomes and costs were weighted. Estimates of disease prevalence, test accuracy and costs were based on two recently performed nationwide cohort studies in The Netherlands., Results: Strategies using fFN testing and CL measurement separately to predict preterm delivery are associated with higher costs and incidence of adverse neonatal outcomes compared with strategies that combine both tests. Additional fFN testing when CL is 15-30 mm was considered cost effective, leading to a cost saving of €3919 per woman when compared with a treat-all strategy, with a small deterioration in neonatal health outcomes, namely one additional perinatal death and 21 adverse outcomes per 10 000 women with signs of preterm labor (incremental cost-effectiveness ratios €39 million and €1.9 million, respectively). Implementing this strategy in The Netherlands, a country with about 180 000 deliveries annually, could lead to an annual cost saving of between €2.4 million and €7.6 million, with only a small deterioration in neonatal health outcomes., Conclusion: In women with symptoms of preterm labor at 24-34 weeks' gestation, performing additional fFN testing when CL is between 15 and 30 mm is a viable and cost-saving strategy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

eHealth can improve healthcare worldwide, and scientific research should provide evidence on the efficacy, safety and added value of such interventions. For successful implementation of eHealth interventions into clinical practice, barriers need to be anticipated. We identified seven barriers by interviewing health professionals in the Dutch healthcare system. These barriers covered three topics: financing, human factors and organizational factors. This paper discusses their potential impact on eHealth uptake. Bridging the gap between studies to assess effective eHealth interventions and their value-based implementation in healthcare is much needed.

Introduction and Hypothesis: Urinary incontinence is a common condition in women, with a reported prevalence ranging from 25% to 51%. Of these women, an estimated 38% suffer from stress urinary incontinence (SUI). A European research consortium is investigating an innovative system based on information and communication technology for the conservative treatment of women with SUI. When introducing a new intervention, implementation barriers arise and need to be identified. Therefore, we investigated healthcare providers' experience with and attitude towards innovative care options., Methods: We performed an online survey to assess (1) the characteristics and practice of healthcare providers, (2) current protocols for SUI, (3) current use of biofeedback, and (4) knowledge about serious gaming. The survey was sent to members of professional societies in Europe (EUGA), UK (BSUG) and The Netherlands (DPFS)., Results: Of 341 questionnaires analyzed (response rate between 18% and 30%), 64% of the respondents had access to a protocol for the treatment of SUI, and 31% used biofeedback when treating patients with SUI. However, 92% considered that biofeedback has a clear or probable added value, and 97% of those who did not use biofeedback would change their practice if research evidence supported its use. Finally, 89% of respondents indicated that they had no experience of serious gaming, but 92% considered that it could be useful., Conclusions: Although inexperienced, European urogynecologists and physical therapists welcome innovative treatment options for the conservative treatment of SUI such as portable wireless biofeedback and serious gaming. Scientific evidence is considered a prerequisite to incorporate such innovations into clinical practice.

Objectives: An antibiotic checklist was introduced in nine Dutch hospitals to improve appropriate antibiotic use. We estimated the cost-effectiveness of checklist use., Methods: We compared 853 patients treated with an antibiotic before checklist introduction (usual care group) with 1207 patients treated after introduction (checklist group). We calculated the change of costs between these groups per unit effect [incremental cost-effectiveness ratio (ICER)]: per extra patient receiving appropriate treatment; and per day reduction in length of hospital stay (LOS). We also calculated the benefit-to-cost ratio per day reduction in LOS. Finally, we estimated the number of checklists after which the expected benefits would compensate for costs in one hospital., Results: The cost of checklist use per patient was €10.10. Of the usual care patients, 48.8% received appropriate antibiotic treatment compared with 67.5% of the checklist patients (+18.7%). The ICER was €54.01 (1010/18.7) per extra patient with appropriate treatment. In a model calculation the expected effect of appropriate antibiotic use was a reduction in LOS of 1.05 days, which was extrapolated to a reduction of 19.64 hospital days per 100 patients. The ICER was €51.43 (1010/19.64) per day reduction in LOS. The estimated benefit of a 1 day reduction was €611. The benefit-to-cost ratio was 11.9 (611/51.43) per day reduction in LOS, indicating a cost saving of €12 for every euro spent on checklist use. The benefits would compensate for costs after use of 11 checklists., Conclusions: Efforts for further implementation of the antibiotic checklist can be justified by potential economic benefits., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To evaluate the cost-effectiveness of a diagnostic laparoscopy prior to primary cytoreductive surgery to prevent futile primary cytoreductive surgery (i.e. leaving >1cm residual disease) in patients suspected of advanced stage ovarian cancer., Methods: An economic analysis was conducted alongside a randomized controlled trial in which patients suspected of advanced stage ovarian cancer who qualified for primary cytoreductive surgery were randomized to either laparoscopy or primary cytoreductive surgery. Direct medical costs from a health care perspective over a 6-month time horizon were analyzed. Health outcomes were expressed in quality-adjusted life-years (QALYs) and utility was based on patient's response to the EQ-5D questionnaires. We primarily focused on direct medical costs based on Dutch standard prices., Results: We studied 201 patients, of whom 102 were randomized to laparoscopy and 99 to primary cytoreductive surgery. No significant difference in QALYs (utility=0.01; 95% CI 0.006 to 0.02) was observed. Laparoscopy reduced the number of futile laparotomies from 39% to 10%, while its costs were € 1400 per intervention, making the overall costs of both strategies comparable (difference € -80 per patient (95% CI -470 to 300)). Findings were consistent across various sensitivity analyses., Conclusion: In patients with suspected advanced stage ovarian cancer, a diagnostic laparoscopy reduced the number of futile laparotomies, without increasing total direct medical health care costs, or adversely affecting complications or quality of life., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the impact of an expansion of liaison psychiatry services (LPS) on patient management, outcomes and treatment costs for emergency department (ED) attendances for self-harm., Design: Retrospective before and after cohort study using routinely collected Self-Harm Surveillance Register data., Setting: A large hospital in South West England., Subjects: Patients attending the ED for self-harm., Interventions: Extension of the LPS' working hours from 9:00 to 17:00, Monday to Friday to 8:00 to 22:00, 7 days a week, following a £250 000 annual investment MAIN OUTCOME MEASURES: Number and characteristics of ED attendances for self-harm. The before and after cohorts were compared in terms of key process measures, including proportion of patients receiving a psychosocial assessment, average length of hospital stay, waiting times for assessment, proportion of patients who self-discharged without an assessment, levels of repeat self-harm attendances and mean cost per patient attendance., Results: 298 patients attended ED for self-harm on 373 occasions between January and March 2014, and 318 patients attended on 381 occasions between January and March 2015. The proportion of ED attendances where patients received a psychosocial assessment increased from 57% to 68% (p=0.003), median waiting time decreased by 3 hours and 14 min (p=0.017), and the proportion of episodes where patients self-discharged without a psychosocial assessment decreased from 20% to 13% (p=0.022). The mean cost per patient attendance was marginally lower after the intervention (-£84; 95% CI -£254 to £77)., Conclusions: The extended LPS seems to have had a favourable effect on the management and outcomes of self-harm patients. The cost of extending the LPS' working hours might be partially offset by more efficient assessment and discharge. The impact of the extended LPS on the care of hospitalised patients with mental health problems other than self-harm requires further evaluation., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: Quality indicators (QIs) have been developed to define appropriate antibiotic use in hospitalized patients. We evaluated whether a checklist based on these QIs affects appropriate antibiotic use and length of hospital stay., Methods: An antibiotic checklist for patients treated with intravenous antibiotics was introduced in nine Dutch hospitals in a stepped wedge cluster randomized trial. Prophylaxis was excluded. We included a random sample before (baseline), and all eligible patients after (intervention) checklist introduction. Baseline and intervention outcomes were compared. Primary endpoint was length of stay (LOS), analysed by intention to treat. Secondary endpoints, including QI performances, QI sum score (performance on all QIs per patient), and quality of checklist use, were analysed per protocol., Results: Between 1 November 2014 and 1 October 2015 we included 853 baseline and 5354 intervention patients, of whom 993 (19%) had a completed checklist. The LOS did not change (baseline geometric mean 10.0 days (95% CI 8.6-11.5) versus intervention 10.1 days (95% CI 8.9-11.5), p 0.8). QI performances increased between +3.0% and +23.9% per QI, and the percentage of patients with a QI sum score above 50% increased significantly (OR 2.4 (95% CI 2.0-3.0), p<0.001). Higher QI sum scores were significantly associated with shorter LOS. Discordance existed between checklist-answers and actual performance., Conclusions: Use of an antibiotic checklist resulted in a significant increase in appropriateness of antibiotic use, but not in a reduction of LOS. Low overall checklist completion rates and discordance between checklist-answers and actual provided care might have attenuated the impact of the checklist., (Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: There are currently no independent data available comparing infliximab and etanercept for the treatment of psoriasis., Objectives: To compare these biologics without funding from pharmaceutical companies., Methods: Overall, 50 patients were randomized to etanercept (n = 23) 50 mg subcutaneously twice weekly or infliximab (n = 25) 5 mg kg -1 intravenously at week 0, 2, 6, 14 and 22. After 24 weeks, 19 patients stopped and 22 continued treatment and were followed up to week 48. The primary outcome was ≥ 75% improvement of Psoriasis Area and Severity Index (PASI 75) at week 24. The secondary outcomes included PASI 75 at week 6 (onset of action) and week 12, Investigator's Global Assessment (IGA), Patient Global Assessment, impact on quality of life (Skindex-17 and SF-36), Treatment Satisfaction Questionnaire of Medication, duration of remission, maintenance treatment and safety., Results: At week 24, PASI 75 was achieved in 72% (infliximab) vs. 35% (etanercept) (P = 0·01). The onset of action was achieved in 52% (infliximab) and 4% (etanercept). At week 12, 76% (infliximab) and 22% (etanercept) achieved PASI 75 (P < 0·001). At week 24, IGA 'clear or almost clear' was observed in 76% (infliximab) and 30% (etanercept) (P = 0·01). Skindex-17 symptom score was significantly better for infliximab. Maintenance treatment achieved PASI 75 for 67% (n = 6) infliximab vs. 50% (n = 5) etanercept, at week 48 (P = 0·65). Mild adverse events were reported in 76% (infliximab) vs. 66% (etanercept)., Conclusions: Infliximab showed a rapid and significant higher level of efficacy until week 24 compared with etanercept. Long-term data showed no significant differences between both groups at week 48. Safety parameters were comparable., (© 2016 British Association of Dermatologists.)

Purpose To investigate whether initial diagnostic laparoscopy can prevent futile primary cytoreductive surgery (PCS) by identifying patients with advanced-stage ovarian cancer in whom > 1 cm of residual disease will be left after PCS. Patients and Methods This multicenter, randomized controlled trial was undertaken within eight gynecologic cancer centers in the Netherlands. Patients with suspected advanced-stage ovarian cancer who qualified for PCS were eligible. Participating patients were randomly assigned to either laparoscopy or PCS. Laparoscopy was used to guide selection of primary treatment: either primary surgery or neoadjuvant chemotherapy followed by interval surgery. The primary outcome was futile laparotomy, defined as a PCS with residual disease of > 1 cm. Primary analyses were performed according to the intention-to-treat principle. Results Between May 2011 and February 2015, 201 participants were included, of whom 102 were assigned to diagnostic laparoscopy and 99 to primary surgery. In the laparoscopy group, 63 (62%) of 102 patients underwent PCS versus 93 (94%) of 99 patients in the primary surgery group. Futile laparotomy occurred in 10 (10%) of 102 patients in the laparoscopy group versus 39 (39%) of 99 patients in the primary surgery group (relative risk, 0.25; 95% CI, 0.13 to 0.47; P < .001). In the laparoscopy group, three (3%) of 102 patients underwent both primary and interval surgery compared with 28 (28%) of 99 patients in the primary surgery group ( P < .001). Conclusion Diagnostic laparoscopy reduced the number of futile laparotomies in patients with suspected advanced-stage ovarian cancer. In women with a plan for PCS, these data suggest that performance of diagnostic laparoscopy first is reasonable and that if cytoreduction to < 1 cm of residual disease seems feasible, to proceed with PCS.

Objective:  To compare the effectiveness of the oxytocin receptor antagonist atosiban with the beta mimetic fenoterol as uterine relaxants in women undergoing external cephalic version (ECV) for breech presentation., Design:  Multicentre, open label, randomised controlled trial., Setting:  Eight hospitals in the Netherlands, August 2009 to May 2014., Participants:  830 women with a singleton fetus in breech presentation and a gestational age of more than 34 weeks were randomly allocated in a 1:1 ratio to either 6.75 mg atosiban (n=416) or 40 μg fenoterol (n=414) intravenously for uterine relaxation before ECV., Main Outcome Measures:  The primary outcome measures were a fetus in cephalic position 30 minutes after the procedure and cephalic presentation at delivery. Secondary outcome measures were mode of delivery, incidence of fetal and maternal complications, and drug related adverse events. All analyses were done on an intention-to-treat basis., Results:  Cephalic position 30 minutes after ECV occurred significantly less in the atosiban group than in the fenoterol group (34% v 40%, relative risk 0.73, 95% confidence interval 0.55 to 0.93). Presentation at birth was cephalic in 35% (n=139) of the atosiban group and 40% (n=166) of the fenoterol group (0.86, 0.72 to 1.03), and caesarean delivery was performed in 60% (n=240) of women in the atosiban group and 55% (n=218) in the fenoterol group (1.09, 0.96 to 1.20). No significant differences were found in neonatal outcomes or drug related adverse events., Conclusions:  In women undergoing ECV for breech presentation, uterine relaxation with fenoterol increases the rate of cephalic presentation 30 minutes after the procedure. No statistically significant difference was found for cephalic presentation at delivery., Trial Registration:  Dutch Trial Register, NTR 1877., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

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.

Objective: To evaluate the effectiveness of hysteroscopy for the detection and treatment of endometrial polyps versus expectant management in women with postmenopausal bleeding (PMB), a thickened endometrium and benign endometrial sampling., Design: Multicentre, randomised controlled trial., Setting: Three academic hospitals and nine non-academic teaching hospitals in the Netherlands., Population: Women with PMB, an endometrial thickness >4 mm and benign result from endometrial sampling., Methods: Women were randomised to either further diagnostic workup by hysteroscopy (preceded by saline infusion sonography) or expectant management., Main Outcomes: The primary outcome measure was recurrence of PMB within a year after randomisation. Secondary outcome measures were time to recurrent bleeding and recurrent bleeding after more than 1 year. In the hysteroscopy group, the presence of polyps and the results of their histology were registered., Results: Between January 2010 and October 2013, 200 women were randomised; 98 to hysteroscopy and 102 to expectant management. Within 1 year a total of 15 women (15.3%) in the hysteroscopy group experienced recurrent bleeding, versus 18 (18.0%) in the expectant management group (relative risk 0.85 (95% CI 0.46-1.59). In the hysteroscopy group, 50/98 (51%) polyps were diagnosed of which 6/98 (6%) showed evidence of endometrial (pre)malignancy; final pathology results after hysterectomy showed three women with hyperplasia with atypia and three women with endometrial cancer., Conclusion: In women with PMB, a thickened endometrium and benign endometrial sampling, operative hysteroscopy does not reduce recurrent bleeding. Hysteroscopy detected focal endometrial (pre)malignancy in 6% of women who had benign endometrial sampling. This finding indicates that in these women, further diagnostic workup is warranted to detect focal (pre)malignancies, missed by blind endometrial sampling., Tweetable Abstract: In women with PMB, hysteroscopy does not reduce recurrent bleeding but is warranted to detect focal malignancy., (© 2016 Royal College of Obstetricians and Gynaecologists.)

Background: Laparoscopic peritoneal lavage is an alternative to sigmoid resection in selected patients presenting with purulent peritonitis from perforated diverticulitis. Although recent trials have lacked superiority for lavage in terms of morbidity, mortality was not compromised, and beneficial secondary outcomes were shown. These included shorter duration of surgery, less stoma formation and less surgical reintervention (including stoma reversal) for laparoscopic lavage versus sigmoid resection respectively. The cost analysis of laparoscopic lavage for perforated diverticulitis in the Ladies RCT was assessed in the present study., Methods: This study involved an economic evaluation of the randomized LOLA (LaparOscopic LAvage) arm of the Ladies trial (comparing laparoscopic lavage with sigmoid resection in patients with purulent peritonitis due to perforated diverticulitis). The actual resource use per individual patient was documented prospectively and analysed (according to intention-to-treat) for up to 1 year after randomization., Results: Eighty-eight patients were randomized to either laparoscopic lavage (46) or sigmoid resection (42). The total medical costs for lavage were lower (mean difference € - 3512, 95 per cent bias-corrected and accelerated c.i. -16 020 to 8149). Surgical reintervention increased costs in the lavage group, whereas stoma reversal increased costs in the sigmoid resection group. Differences in favour of laparoscopy were robust when costs were varied by ±20 per cent in a sensitivity analysis (mean cost difference € - 2509 to -4438)., Conclusion: Laparoscopic lavage for perforated diverticulitis is more cost-effective than sigmoid resection., (© 2016 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.)

As a result of increasing digitisation of medical record keeping, electronic health records (EHRs) are an attractive source for data reuse. However, such record-based research is still suffering from poor quality of data stored in EHRs. Lack of consent for reuse of data also plays an impeding role, especially in retrospective record-based research. That said, increasing cooperation between healthcare institutions and current attention for EHR organisation also offer opportunities for record-based research. Patient data can be recorded in more standardised ways and in increasingly harmonised EHRs. In addition, if healthcare institutions were to establish a generic consent procedure - preferably with national scope - the potential of EHRs for scientific research could be exploited in considerably better ways.

Objective: To evaluate whether in symptomatic women, the combination of quantitative fetal fibronectin (fFN) testing and cervical length (CL) improves the prediction of preterm delivery (PTD) within 7 days compared with qualitative fFN and CL., Design: Post hoc analysis of frozen fFN samples of a nationwide cohort study., Setting: Ten perinatal centres in the Netherlands., Population: Symptomatic women between 24 and 34 weeks of gestation., Methods: The risk of PTD <7 days was estimated in predefined CL and fFN strata. We used logistic regression to develop a model including quantitative fFN and CL, and one including qualitative fFN (threshold 50 ng/ml) and CL. We compared the models' capacity to identify women at low risk (<5%) for delivery within 7 days using a reclassification table., Main Outcome Measures: Spontaneous delivery within 7 days after study entry., Results: We studied 350 women, of whom 69 (20%) delivered within 7 days. The risk of PTD in <7 days ranged from 2% in the lowest fFN group (<10 ng/ml) to 71% in the highest group (>500 ng/ml). Multivariable logistic regression showed an increasing risk of PTD in <7 days with rising fFN concentration [10-49 ng/ml: odds ratio (OR) 1.3, 95% confidence interval (95% CI) 0.23-7.0; 50-199 ng/ml: OR 3.2, 95% CI 0.79-13; 200-499 ng/ml: OR 9.0, 95% CI 2.3-35; >500 ng/ml: OR 39, 95% CI 9.4-164] and shortening of the CL (OR 0.86 per mm, 95% CI 0.82-0.90). Use of quantitative fFN instead of qualitative fFN resulted in reclassification of 18 (5%) women from high to low risk, of whom one (6%) woman delivered within 7 days., Conclusion: In symptomatic women, quantitative fFN testing does not improve the prediction of PTD within 7 days compared with qualitative fFN testing in combination with CL measurement in terms of reclassification from high to low (<5%) risk, but it adds value across the risk range., Tweetable Abstract: Quantitative fFN testing adds value to qualitative fFN testing with CL measurement in the prediction of PTD., (© 2015 Royal College of Obstetricians and Gynaecologists.)

Objective: The objective of this study is to evaluate the relation among fetal gender, ethnicity, and preterm labor (PTL) and preterm delivery (PTD)., Methods: A secondary analysis was performed of a prospective cohort study including women with symptoms of PTL between 24 and 34 weeks. The proportion of women carrying a male or female fetus at the onset of PTL was calculated. Gestational age at delivery and risk of PTD of both fetal genders was compared and interaction of fetal gender and maternal ethnicity on the risk of PTD was evaluated., Results: Of the 594 included women, 327 (55%) carried a male fetus. Median gestational age at delivery in women pregnant with a male fetus was 37 5/7 (IQR 34 4/7-39 1/7) weeks compared with 38 1/7 (IQR 36 0/7-39 5/7) weeks in women pregnant with a female fetus (p = 0.032). The risk of PTD did not differ significantly. In Caucasians, we did find an increased risk of PTD before 37 weeks in women pregnant with a male fetus (OR 1.9 (95% CI 1.2-3.0))., Conclusions: The majority of women with PTL are pregnant with a male fetus and these women deliver slightly earlier. Race seems to affect this disparity.

Study Question: Is curettage more effective than expectant management in case of an incomplete evacuation after misoprostol treatment for first trimester miscarriage?, Summary Answer: Curettage leads to a higher chance of complete evacuation but expectant management is successful in at least 76% of women with an incomplete evacuation of the uterus after misoprostol treatment for first trimester miscarriage., What Is Known Already: In 5-50% of the women treated with misoprostol, there is a suspicion of incomplete evacuation of the uterus on sonography. Although these women generally have minor symptoms, such a finding often leads to additional curettage., Study Design, Size, Duration: From June 2012 until July 2014, we conducted a nationwide multicenter randomized controlled trial (RCT). Women who had had primary misoprostol treatment for miscarriage with sonographic evidence of incomplete evacuation of the uterus were randomly allocated to either curettage or expectant management (1:1), using a web-based application., Participants/materials, Setting, Methods: We included 59 women in 27 hospitals; 30 were allocated to curettage and 29 were allocated to expectant management. A successful outcome was defined as sonographic finding of an empty uterus 6 weeks after randomization., Main Results and the Role of Chance: Baseline characteristics of both groups were comparable. Empty uterus on sonography or uneventful clinical follow-up was seen in 29/30 women (97%) allocated to curettage compared with 22/29 women (76%) allocated to expectant management (RR 1.3, 95% CI 1.03-1.6) with complication rates of 10% versus 10%, respectively (RR 0.97, 95% CI 0.21-4.4). In the group allocated to curettage, no woman required re-curettage, while two women (6.7%) underwent hysteroscopy (for other or unknown reasons). In the women allocated to expectant management, curettage was performed in four women (13.8%) and three women (10.3%) underwent hysteroscopy., Limitations, Reasons for Caution: Due to a strong patient preference, mainly for expectant management, the targeted sample size could not be included and the trial was stopped prematurely., Wider Implications of the Findings: In women suspected of incomplete evacuation of the uterus after misoprostol, curettage is more effective than expectant management. However, expectant management is equally safe and prevents curettage for most of the women. This finding could further restrain the use of curettage in the treatment of first trimester miscarriage., Study Funding/competing Interests: This study was funded by ZonMw, a Dutch organization for Health Research and Development, project number 80-82310-97-12066. There were no conflicts of interests., Trial Registration Number: Dutch Trial Register NTR3310, http://www.trialregister.nl TRIAL REGISTRATION DATE: 27 February 2012., Date of First Patient's Enrolment: 12 June 2012., (© The Author 2016. 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 compare the accuracy of the Actim Partus test and fetal fibronectin (fFN) test in the prediction of spontaneous preterm delivery within seven days in symptomatic women undergoing cervical length measurement., Study Design: We performed a post-hoc analysis on frozen samples of a nationwide cohort study in all 10 perinatal centres in the Netherlands. We selected samples from women with signs of preterm labour between 24 and 34 weeks of gestational age and a cervical length below 30mm. Delivery within seven days after initial assessment was the primary endpoint. We calculated sensitivity, specificity, and positive and negative predictive values for the combination of both the Actim Partus test and fFN test with cervical length. A test was considered positive in case of a cervical length between 15 and 30mm with a positive Actim Partus or fFN test, and a cervical length below 15mm regardless the test result., Results: In total, samples of 350 women were tested, of whom 69 (20%) delivered within seven days. Eighty-four women had a positive Actim Partus test and 162 women a positive fFN test, of whom 54 (64%) and 63 (39%) delivered within seven days, respectively. Ninety-seven women had a cervical length below 15mm, of whom 50 (52%) delivered within seven days. Sensitivity, specificity, positive and negative predictive values of combining cervical length with the Actim Partus test or the fFN test were 91%, 75%, 47% and 97%, and 96%, 58%, 36% and 98%, respectively., Conclusion: According to this post-hoc study, in combination with cervical length, the Actim Partus test could be used as an alternative for the fFN test to identify women who will not deliver within seven days after presentation. Further evidence should be collected in a prospective comparative study., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: Electronic foetal monitoring (EFM) together with non-invasive ST-analysis (STAN) has been suggested as a superior technique to EFM alone for foetal surveillance to prevent metabolic acidosis. This study aims to compare the cost-effectiveness of these two techniques from both maternal (short term) as neonatal (long term) perspective to guide clinical decision-making., Methods: We created two models: a maternal model, focused on the difference in mode of delivery as most important outcome, and a neonatal Markov model focused on the differences in metabolic acidosis - and its relationship to cerebral palsy (CP) - as the most relevant outcome to estimate the long-term cost-effectiveness. The cost to prevent one instrumental delivery was estimated in the maternal model. The costs to prevent one metabolic acidosis and the costs per quality adjusted life years were calculated in the neonatal model., Results: The average costs of STAN are only €34 higher when compared to EFM alone. From maternal perspective the cost of preventing one instrumental delivery was estimated at €2602. From neonatal perspective the cost to prevent one case of metabolic acidosis was €14 509. Over the long term, STAN becomes a dominant (cost saving) strategy if >1% of the patients exposed to metabolic acidosis acquire CP., Conclusions: Our study suggests that STAN, when compared to EFM alone, can be a cost-effective strategy from both a maternal and neonatal perspective.

Importance: Although numerous children receive methylphenidate hydrochloride for the treatment of attention-deficit/hyperactivity disorder (ADHD), little is known about age-dependent and possibly lasting effects of methylphenidate on the human dopaminergic system., Objectives: To determine whether the effects of methylphenidate on the dopaminergic system are modified by age and to test the hypothesis that methylphenidate treatment of young but not adult patients with ADHD induces lasting effects on the cerebral blood flow response to dopamine challenge, a noninvasive probe for dopamine function., Design, Setting, and Participants: A randomized, double-blind, placebo-controlled trial (Effects of Psychotropic Drugs on Developing Brain-Methylphenidate) among ADHD referral centers in the greater Amsterdam area in the Netherlands between June 1, 2011, and June 15, 2015. Additional inclusion criteria were male sex, age 10 to 12 years or 23 to 40 years, and stimulant treatment-naive status., Interventions: Treatment with either methylphenidate or a matched placebo for 16 weeks., Main Outcomes and Measures: Change in the cerebral blood flow response to an acute challenge with methylphenidate, noninvasively assessed using pharmacological magnetic resonance imaging, between baseline and 1 week after treatment. Data were analyzed using intent-to-treat analyses., Results: Among 131 individuals screened for eligibility, 99 patients met DSM-IV criteria for ADHD, and 50 participants were randomized to receive methylphenidate and 49 to placebo. Sixteen weeks of methylphenidate treatment increased the cerebral blood flow response to methylphenidate within the thalamus (mean difference, 6.5; 95% CI, 0.4-12.6; P = .04) of children aged 10 to 12 years old but not in adults or in the placebo group. In the striatum, the methylphenidate condition differed significantly from placebo in children but not in adults (mean difference, 7.7; 95% CI, 0.7-14.8; P = .03)., Conclusions and Relevance: We confirm preclinical data and demonstrate age-dependent effects of methylphenidate treatment on human extracellular dopamine striatal-thalamic circuitry. Given its societal relevance, these data warrant replication in larger groups with longer follow-up., Trial Registration: identifier: NL34509.000.10 and trialregister.nl identifier: NTR3103., Competing Interests: Disclosures: Dr Niessen reported being cofounder, shareholder, and part-time scientific officer of Quantib BV. No other disclosures were reported.

Objective: to assess the mode of childbirth and adverse neonatal outcomes in women with a breech presentation with or without an external cephalic version attempt, and to compare the mode of childbirth among women with successful ECV to women with a spontaneous cephalic presentation., Design: prospective matched cohort study., Setting: 25 clusters (hospitals and its referring midwifery practices) in the Netherlands. Data of the Netherlands perinatal registry for the matched cohort., Participants: singleton pregnancies from January 2011 to August 2012 with a fetus in breech presentation and a childbirth from 36 weeks gestation onwards. Spontaneous cephalic presentations (selected from national registry 2009 and 2010) were matched in a 2:1 ratio to cephalic presentations after a successful version attempt. Matching criteria were maternal age, parity, gestational age at childbirth and fetal gender. Main outcomes were mode of childbirth and neonatal outcomes., Measurements and Findings: of 1613 women eligible for external cephalic version, 1169 (72.5%) received an ECV attempt. The overall caesarean childbirth rate was significantly lower compared to women who did not receive a version attempt (57% versus 87%; RR 0.66 (0.62-0.70)). Women with a cephalic presentation after ECV compared to women with a spontaneous cephalic presentation had a decreased risk for instrumental vaginal childbirth (RR 0.52 (95% CI 0.29-0.94)) and an increased risk of overall caesarean childbirth (RR 1.7 (95%CI 1.2-2.5))., Key Conclusions: women who had a successful ECV are at increased risk for a caesarean childbirth but overall, ECV is an important tool to reduce the caesarean rate., Implication for Practice: ECV is an important tool to reduce the caesarean section rates., (Copyright © 2016. Published by Elsevier Ltd.)

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: In women with threatened preterm birth, delay of delivery by 48 h allows antenatal corticosteroids to improve neonatal outcomes. For this reason, tocolytics are often administered for 48 h; however, there is no consensus about which drug results in the best maternal and neonatal outcomes. In the APOSTEL III trial we aimed to compare the effectiveness and safety of the calcium-channel blocker nifedipine and the oxytocin inhibitor atosiban in women with threatened preterm birth., Methods: We did this multicentre, randomised controlled trial in ten tertiary and nine teaching hospitals in the Netherlands and Belgium. Women with threatened preterm birth (gestational age 25-34 weeks) were randomly assigned (1:1) to either oral nifedipine or intravenous atosiban for 48 h. An independent data manager used a web-based computerised programme to randomly assign women in permuted block sizes of four, with groups stratified by centre. Clinicians, outcome assessors, and women were not masked to treatment group. The primary outcome was a composite of adverse perinatal outcomes, which included perinatal mortality, bronchopulmonary dysplasia, sepsis, intraventricular haemorrhage, periventricular leukomalacia, and necrotising enterocolitis. Analysis was done in all women and babies with follow-up data. The study is registered at the Dutch Clinical Trial Registry, number NTR2947., Findings: Between July 6, 2011, and July 7, 2014, we randomly assigned 254 women to nifedipine and 256 to atosiban. Primary outcome data were available for 248 women and 297 babies in the nifedipine group and 255 women and 294 babies in the atosiban group. The primary outcome occurred in 42 babies (14%) in the nifedipine group and in 45 (15%) in the atosiban group (relative risk [RR] 0·91, 95% CI 0·61-1·37). 16 (5%) babies died in the nifedipine group and seven (2%) died in the atosiban group (RR 2·20, 95% CI 0·91-5·33); all deaths were deemed unlikely to be related to the study drug. Maternal adverse events did not differ between groups., Interpretation: In women with threatened preterm birth, 48 h of tocolysis with nifedipine or atosiban results in similar perinatal outcomes. Future clinical research should focus on large placebo-controlled trials, powered for perinatal outcomes., Funding: ZonMw (the Netherlands Organisation for Health Research and Development)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Postmenopausal bleeding (PMB) can be the first sign of endometrial cancer. In case of thickened endometrium, endometrial sampling is often used in these women. In this systematic review, we studied the accuracy of endometrial sampling for the diagnoses of endometrial cancer, atypical hyperplasia and endometrial disease (endometrial pathology, including benign polyps). We systematically searched the literature for studies comparing the results of endometrial sampling in women with postmenopausal bleeding with two different reference standards: blind dilatation and curettage (D&C) and hysteroscopy with histology. We assessed the quality of the detected studies by the QUADAS-2 tool. For each included study, we calculated the fraction of women in whom endometrial sampling failed. Furthermore, we extracted numbers of cases of endometrial cancer, atypical hyperplasia and endometrial disease that were identified or missed by endometrial sampling. We detected 12 studies reporting on 1029 women with postmenopausal bleeding: five studies with dilatation and curettage (D&C) and seven studies with hysteroscopy as a reference test. The weighted sensitivity of endometrial sampling with D&C as a reference for the diagnosis of endometrial cancer was 100% (range 100-100%) and 92% (71-100) for the diagnosis of atypical hyperplasia. Only one study reported sensitivity for endometrial disease, which was 76%. When hysteroscopy was used as a reference, weighted sensitivities of endometrial sampling were 90% (range 50-100), 82% (range 56-94) and 39% (21-69) for the diagnosis of endometrial cancer, atypical hyperplasia and endometrial disease, respectively. For all diagnosis studied and the reference test used, specificity was 98-100%. The weighted failure rate of endometrial sampling was 11% (range 1-53%), while insufficient samples were found in 31% (range 7-76%). In these women with insufficient or failed samples, an endometrial (pre) cancer was found in 7% (range 0-18%). In women with postmenopausal bleeding, the sensitivity of endometrial sampling to detect endometrial cancer and especially atypical hyperplasia and endometrial disease, including endometrial polyps, is lower than previously thought. Therefore, further diagnostic work-up for focal pathology is warranted, after a benign result of endometrial sampling., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Objective: To determine whether structured assessment of outpatient endometrial biopsies decreases the number of inconclusive samples., Design: Retrospective cohort study., Setting: Single hospital pathology laboratory., Population: Endometrial biopsy samples of 66 women with postmenopausal bleeding, collected during the usual diagnostic work-up and assessed as insufficient for a reliable histological diagnosis., Methods: Endometrial biopsy samples were requested from the pathology laboratories. The retrieved samples were systematically reassessed by a single pathologist specialized in gynecology., Main Outcome Measure: Disagreement between initial assessment and conclusion after structured reassessment., Results: We retrieved 36 of 66 endometrial biopsy samples from six different pathology laboratories. Structured reassessment of the retrieved samples by a single pathologist specialized in gynecology did not change the conclusion in 35 of the 36 samples. The remaining sample contained a large amount of endometrial tissue and the diagnosis at reassessment was endometrial hyperplasia without atypia. All other samples contained insufficient material for a reliable diagnosis., Conclusion: A structured reassessment of endometrial biopsies samples, which were classified as inconclusive due to insufficient material, did not change the conclusion. Although it might be helpful for pathologists to have diagnostic criteria for adequacy and/or inadequacy of an endometrial biopsy sample, the gain in efficiency is likely to be small.

Objective: To assess the effect of maintenance tocolysis in women who are at high or low risk for preterm delivery according to fetal fibronectin (fFN) status and cervical length (CL)., Study Design: We compared the risk of preterm delivery in fFN pos and fFN neg women and in women with a CL <15 mm and ≥15 mm, by using the Cox regression. Differences between the effectiveness of maintenance tocolysis in high- and low-risk women were assessed by using an interaction term., Results: 122 fFN tests were taken, of which 50 were fFN pos. CL was measured in 236 women, of whom 52 women had a CL <15 mm. The median gestational age at delivery was lower in fFN pos women; fFN pos women had a higher hazard for preterm delivery at any point of time (HR 4.7; 95% CI 2.9 to 7.6). Comparable results were seen for CL. Neither fFN status nor CL did alter the effect of maintenance tocolysis, which was ineffective in the total randomized group, on the risk of preterm delivery (p for interaction = 0.87 for fFN and 0.18 for CL)., Conclusion: Maintenance tocolytic therapy with nifedipine is ineffective and not dependent on fFN or CL status.

Objective: To compare the effectiveness of two strategies to improve antibiotic use in patients with a complicated urinary tract infection., Design: Multicentre cluster randomised unblinded trial., Method: The departments of Internal Medicine and Urology from 19 hospitals in the Netherlands took part in this trial. Based on retrospective patient record investigations we performed baseline measurements on the scores of a validated set of quality indicators for antibiotic use in a minimum of 50 patients with a complicated urinary tract infection per department in 2009. A similar post-trial measurement took place in 2012. In 2010 we randomised the hospitals between 2 improvement strategies: a multifaceted strategy that included results of the baseline measurements, education, reminders and assistance with optional improvement interventions, and a competitive feedback strategy, in which the departments only received results of the baseline measurements and non-anonymous results from the other departments in this study arm. The primary outcome measure was improvement of the quality indicator scores. Secondary outcome measures were determinants of improvement of the indicators. (Netherlands Trial Register: NTR1742) RESULTS: The baseline and post-trial measurements were performed on 1,964 patients and 2,027 patients, respectively. Post-trial measurements revealed a significant, but limited, improvement of several indicators compared with baseline measurements. We found no significant difference in improvement between the two strategies for any indicator. The intensity with which the departments implemented improvement strategies was mostly suboptimal, but intensive implementation of a strategy was associated with greater improvement., Conclusion: The effectiveness of both improvement strategies was comparable, but limited. For real improvement in antibiotic use in patients with complicated urinary tract infections, improvement interventions should be developed and applied by local professionals themselves.

Study Question: Could dilatation and curettage (D&C), used in the treatment of miscarriage and termination of pregnancy, increase the risk of subsequent preterm birth?, Summary Answer: A history of curettage in women is associated with an increased risk of preterm birth in a subsequent pregnancy compared with women without such history., What Is Known Already: D&C is one of the most frequently performed procedures in obstetrics and gynaecology. Apart from the acknowledged but relatively rare adverse effects, such as cervical tears, bleeding, infection, perforation of the uterus, bowel or bladder, or Asherman syndrome, D&C has been suggested to also lead to an increased risk of preterm birth in the subsequent pregnancy., Study Design, Size, Duration: In the absence of randomized data, we conducted a systematic review and meta-analysis of cohort and case-control studies., Participants/materials, Setting, Methods: We searched OVID MEDLINE and OVID EMBASE form inception until 21 May 2014. We selected cohort and case-control studies comparing subsequent preterm birth in women who had a D&C for first trimester miscarriage or termination of pregnancy and a control group of women without a history of D&C., Main Results and the Role of Chance: We included 21 studies reporting on 1 853 017 women. In women with a history of D&C compared with those with no such history, the odds ratio (OR) for preterm birth <37 weeks was 1.29 (95% CI 1.17; 1.42), while for very preterm birth the ORs were 1.69 (95% CI 1.20; 2.38) for <32 weeks and 1.68 (95% CI 1.47; 1.92) for <28 weeks. The risk remained increased when the control group was limited to women with a medically managed miscarriage or induced abortion (OR 1.19, 95% CI 1.10; 1.28). For women with a history of multiple D&Cs compared with those with no D&C, the OR for preterm birth (<37 weeks) was 1.74 (95% CI 1.10; 2.76). For spontaneous preterm birth, the OR was 1.44 (95% CI 1.22; 1.69) for a history of D&C compared with no such history., Limitations, Reasons for Caution: There were no randomized controlled trials comparing women with and without a history of D&C and subsequent preterm birth. As a consequence, confounding may be present since the included studies were either cohort or case-control studies, not all of which corrected the results for possible confounding factors., Wider Implications of the Findings: This meta-analysis shows that D&C is associated with an increased risk of subsequent preterm birth. The increased risk in association with multiple D&Cs indicates a causal relationship. Despite the fact that confounding cannot be excluded, these data warrant caution in the use of D&C for miscarriage and termination of pregnancy, the more so since less invasive options are available., Study Funding/competing Interests: This study was funded by ZonMw, a Dutch organization for Health Research and Development, project number 80-82310-97-12066., (© The Author 2015. 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.)

Background: Up to 50% of hospital antibiotic use is inappropriate and therefore improvement strategies are urgently needed. We compared the effectiveness of two strategies to improve the quality of antibiotic use in patients with a complicated urinary tract infection (UTI)., Methods: In a multicentre, cluster-randomized trial 19 Dutch hospitals (departments Internal Medicine and Urology) were allocated to either a multi-faceted strategy including feedback, educational sessions, reminders and additional/optional improvement actions, or a competitive feedback strategy, i.e. providing professionals with non-anonymous comparative feedback on the department's appropriateness of antibiotic use. Retrospective baseline- and post-intervention measurements were performed in 2009 and 2012 in 50 patients per department, resulting in 1,964 and 2,027 patients respectively. Principal outcome measures were nine validated guideline-based quality indicators (QIs) that define appropriate antibiotic use in patients with a complicated UTI, and a QI sumscore that summarizes for each patient the appropriateness of antibiotic use., Results: Performance scores on several individual QIs showed improvement from baseline to post-intervention measurements, but no significant differences were found between both strategies. The mean patient's QI sum score improved significantly in both strategy groups (multi-faceted: 61.7% to 65.0%, P = 0.04 and competitive feedback: 62.8% to 66.7%, P = 0.01). Compliance with the strategies was suboptimal, but better compliance was associated with more improvement., Conclusion: The effectiveness of both strategies was comparable and better compliance with the strategies was associated with more improvement. To increase effectiveness, improvement activities should be rigorously applied, preferably by a locally initiated multidisciplinary team., Trial Registration: Nederlands Trial Register 1742.

Objective: Cervical length (CL) is associated with the risk of preterm birth (PTB) in multiple pregnancies. However, the position of CL within the pathophysiological pathway of PTB is unclear, and it is unknown which factors are predictive for CL. This study aims to investigate whether in twin pregnancies baseline maternal and obstetrical characteristics are potential indicators for CL, to improve insight in the pathophysiological pathway of PTB., Study Design: Secondary analysis of data on twin pregnancies and CL measurement between 16 and 22 weeks. A set of 10 potential indicators, known to be associated with an increased risk of PTB and/or which have a plausible mechanism resulting in a change of CL were selected. We used multivariable linear regression with backward selection to identify independent indicators for CL., Results: A total of 1,447 women with twin pregnancies were included. Mean CL was 43.7 (±8.9) mm. In multivariable analysis, age (0.27 mm/y; 95% confidence interval [CI] 0.16 to 0.39), use of assisted reproductive technologies (ART) (-1.42 mm, 95% CI -2.6 to -0.25), and having delivered at term in a previous pregnancy (1.32 mm, 95% CI 0.25 to 2.39) were significantly associated with CL., Conclusion: This study shows that in twin pregnancies, age, use of ART and having delivered term in a previous pregnancy has an association with CL., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To assess the impact of cervical length (CL) measurement and fetal fibronectin testing (fFN) on the clinicians' decision to prescribe antenatal corticosteroids (ACS) to women with symptoms of preterm labor., Study Design: This is a secondary analysis of a prospective cohort study including women with symptoms of preterm labor and intact membranes between 24 and 34 weeks' gestation. We compared the proportion prescribed and completed ACS courses, preterm delivery within seven days and median intervals from ACS to delivery in four groups: group 1 CL<10 mm, group 2 CL 10-30 mm and positive fFN, group 3 CL 10-30 mm and negative fFN, group 4 CL>30 mm., Results: ACS were prescribed to 63/65 (97%) women in group 1, 176/192 (91%) in group 2, 111/172 women (65%) in group 3 and 55/242 (23%) in group 4. In group 1, 42 (65%) women delivered within seven days, compared to 34 (18%) in group 2, 6 (3%) in group 3 and 3 (1%) in group 4. Median intervals between ACS and delivery were 6 days (IQR 3-61 days), 44 days (IQR 17-69 days), 53 days (IQR 37-77 days) and 66 days (IQR 43-78 days) in group 1, 2, 3 and 4 respectively., Conclusion: ACS were prescribed frequently to women with a CL of 10-30 mm and a negative fFN test or a CL>30 mm. There is room for improvement in the prescription of ACS in these low risk women., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: To assess whether patient characteristics add to the fetal fibronectin test and cervical length measurement in the prediction of preterm delivery in symptomatic women., Study Design: A nationwide prospective cohort study was conducted in all ten perinatal centres in the Netherlands. Women with symptoms of preterm labour between 24 and 34 weeks gestation with intact membranes were invited. In all women qualitative fibronectin testing (0.050 μg/mL cut-off) and cervical length measurement were performed. Only singleton pregnancies were included in this analysis. Logistic regression was used to construct two multivariable models to predict spontaneously delivery within 7 days: a model including cervical length and fetal fibronectin as predictors, and an extended model including all potential predictors. The models were internally validated using bootstrapping techniques. Predictive performances were assessed as the area under the receiver operator characteristic curve (AUC) and calibration plots. We compared the models' capability to identify women with a low risk to deliver within 7 days. 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: Seventy-three of 600 included women (12%) had delivered spontaneously within 7 days. The extended model included maternal age, parity, previous preterm delivery, vaginal bleeding, C-reactive protein, cervical length, dilatation and fibronectin status. Both models had high discriminative performances (AUC of 0.92 (95% CI 0.88-0.95) and 0.95 (95% CI 0.92-0.97) respectively). Compared to the model with fibronectin and cervical length, our extended model reclassified 38 women (6%) from low risk to high risk and 21 women (4%) from high risk to low risk. Preterm delivery within 7 days occurred once in both the reclassification groups., Conclusion: In women with symptoms of preterm labour before 34 weeks gestation, a model that integrates maternal characteristics, clinical signs and laboratory tests, did not predict delivery within 7 days better than a model with only fibronectin and cervical length., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Posttraumatic stress disorder (PTSD) can be a debilitating disorder and often co-occurs with other psychiatric disorders, such as mood, behavioral, and anxiety disorders. Early identification of PTSD and psychiatric comorbidity is highly relevant in order to offer children appropriate and timely treatment. The Children's Revised Impact of Event Scale (CRIES-13) is a reliable and valid self-report measure designed to screen children for PTSD. However, this measure is not useful as a screen for psychiatric comorbidity in children with probable PTSD., Objective: This study evaluated the screening accuracy of the CRIES-Plus, that is, the CRIES-13 combined with 12 additional items to detect psychiatric comorbidity., Method: The CRIES-Plus was completed by 398 Dutch children (7-18 years) exposed to various traumatic events. Psychiatric diagnoses were assessed using the Anxiety Disorders Interview Schedule for DSM-IV: Child version., Results: Six additional items were significantly associated with mood disorders, three items were associated with behavioral disorders, and five items with anxiety disorders. Additional items associated with mood and anxiety disorders demonstrated good discriminatory ability, with cut-off scores of ≥14 and ≥10, respectively. Items associated with behavioral disorders had poor to fair discriminatory ability, with no clear cut-off point., Conclusions: Our findings support the use of the CRIES-Plus to screen for PTSD and comorbid disorders which may help clinicians in assigning appropriate follow-up diagnostic and clinical care.

Objective: To stratify the risk of spontaneous preterm delivery using cervical length (CL) and fetal fibronectin (fFN) in women with threatened preterm labor who remained pregnant after 7 days., Design: Prospective observational study., Setting: Nationwide cohort of women with threatened preterm labor from the Netherlands., Population: Women with threatened preterm labor between 24 and 34 weeks with a valid CL and fFN measurement and remaining pregnant 7 days after admission., Methods: Kaplan-Meier and Cox proportional hazards models were used to estimate cumulative percentages and hazard ratios (HR) for spontaneous delivery., Main Outcome Measures: Spontaneous delivery between 7 and 14 days after initial presentation and spontaneous preterm delivery before 34 weeks., Results: The risk of delivery between 7 and 14 days was significantly increased for women with a CL < 15 mm or a CL ≥15 to <30 mm and a positive fFN, compared with women with a CL ≥30 mm: HR 22.3 [95% confidence interval (CI) 2.6-191] and 14 (95% CI 1.8-118), respectively. For spontaneous preterm delivery before 34 weeks the risk was increased for women with a CL < 15 mm [HR 6.3 (95% CI 2.6-15)] or with a CL ≥15 to <30 mm with either positive fFN [HR 3.6 (95% CI 1.5-8.7)] or negative fFN [HR 3.0 (95% CI 1.2-7.1)] compared with women with a CL ≥ 30 mm., Conclusions: In women remaining pregnant 7 days after threatened preterm labor, CL and fFN results can be used in risk stratification for spontaneous delivery., (© 2015 Nordic Federation of Societies of Obstetrics and Gynecology.)

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.