Brent C. Opmeer

(Lancet. 2016;387:2117–2124) Research has shown that preterm birth accounts for 50% of neonatal morbidity and 50% to 75% of neonatal mortality worldwide.

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. 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. 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. Dutch trial registry: NTR6015 . Registered 9 August 2016.

(Abstracted from Lancet 2016;387:2117–2124) Preterm birth is estimated to affect between 5% and 13% of all pregnancies and is the reason for more than 50% of neonatal morbidity and 50% and 75% of neonatal mortality cases worldwide. It causes long-term physical and developmental impairment, thus having a substantial burden on families and health care costs.

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. 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. 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 is registered at the Dutch Trial Register: http://www.trialregister.nl , NTR4210, date of registration: October 16th 2013.

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.Carolien Roos, Jolande Y. Vis, Hubertina C.J. Scheepers, Kitty W.M. Bloemenkamp, Hans J.J. Duvekot, Jim van Eyck, Christianne de Groot, Joke H. Kok, Brent C. Opmeer, Martijn A. Oudijk, Dimitri N.M. Papatsonis, Martina M. Porath, Krystyna Sollie, Marc E.A. Spaanderman, Fred K. Lotgering, Joris A.M. van der Post, and Ben Willem J. Mo

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. 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. 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. 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. PROSPERO CRD42013006362

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). 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. 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. 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.

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. 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. 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. Dutch trial registry: NTR4872

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.