Showing papers by "Ewoud Schuit published in 2017"

Prospective Risk of Stillbirth and Neonatal Complications in Twin Pregnancies: Systematic Review and Meta-analysis

Abstract: F. Cheong-See, E. Schuit, D. Arroyo-Manzano, A. Khalil, J. Barrett, K.S. Joseph, E. Asztalos, K. Hack, L. Lewi, A. Lim, S. Liem, J.E. Norman, J. Morrison, C.A. Combs, T.J. Garite, K. Maurel, V. Serra, A. Perales, L. Rode, K. Worda, A. Nassar, M. Aboulghar, D. Rouse, E. Thom, F. Breathnach, S. Nakayama, F.M. Russo, J.N. Robinson, J.M. Dodd, R.B. Newman, S. Bhattacharya, S. Tang, B.W. Mol, J. Zamora, B. Thilaganathan, S. Thangaratinam, and Global Obstetrics Network (GONet) Collaboration

Pharmacotherapy for smoking cessation: effects by subgroup defined by genetically informed biomarkers

Abstract: Background Smoking cessation therapies are not effective for all smokers, and researchers are interested in identifying those subgroups of individuals (e.g. based on genotype) who respond best to specific treatments. Objectives To assess whether quit rates vary by genetically informed biomarkers within pharmacotherapy treatment arms and as compared with placebo. To assess the effects of pharmacotherapies for smoking cessation in subgroups of smokers defined by genotype for identified genome-wide significant polymorphisms. Search methods We searched the Cochrane Tobacco Addiction Group specialised register, clinical trial registries, and genetics databases for trials of pharmacotherapies for smoking cessation from inception until 16 August 2016. Selection criteria We included randomised controlled trials (RCTs) that recruited adult smokers and reported pharmacogenomic analyses from trials of smoking cessation pharmacotherapies versus controls. Eligible trials included those with data on a priori genome-wide significant (P < 5 × 10-8) single-nucleotide polymorphisms (SNPs), replicated non-SNPs, and/or the nicotine metabolite ratio (NMR), hereafter collectively described as biomarkers. Data collection and analysis We used standard methodological procedures expected by Cochrane. The primary outcome was smoking abstinence at six months after treatment. The secondary outcome was abstinence at end of treatment (EOT). We conducted two types of meta-analyses- one in which we assessed smoking cessation of active treatment versus placebo within genotype groups, and another in which we compared smoking cessation across genotype groups within treatment arms. We carried out analyses separately in non-Hispanic whites (NHWs) and non-Hispanic blacks (NHBs). We assessed heterogeneity between genotype groups using T², I², and Cochrane Q statistics. Main results Analyses included 18 trials including 9017 participants, of whom 6924 were NHW and 2093 NHB participants. Data were available for the following biomarkers: nine SNPs (rs1051730 (CHRNA3); rs16969968, rs588765, and rs2036527 (CHRNA5); rs3733829 and rs7937 (in EGLN2, near CYP2A6); rs1329650 and rs1028936 (LOC100188947); and rs215605 (PDE1C)), two variable number tandem repeats (VNTRs; DRD4 and SLC6A4), and the NMR. Included data produced a total of 40 active versus placebo comparisons, 16 active versus active comparisons, and 64 between-genotype comparisons within treatment arms. For those meta-analyses showing statistically significant heterogeneity between genotype groups, we found the quality of evidence (GRADE) to be generally moderate. We downgraded quality most often because of imprecision or risk of bias due to potential selection bias in genotyping trial participants. Comparisons of relative treatment effects by genotype For six-month abstinence, we found statistically significant heterogeneity between genotypes (rs16969968) for nicotine replacement therapy (NRT) versus placebo at six months for NHB participants (P = 0.03; n = 2 trials), but not for other biomarkers or treatment comparisons. Six-month abstinence was increased in the active NRT group as compared to placebo among participants with a GG genotype (risk ratio (RR) 1.47, 95% confidence interval (CI) 1.07 to 2.03), but not in the combined group of participants with a GA or AA genotype (RR 0.43, 95% CI 0.15 to 1.26; ratio of risk ratios (RRR) GG vs GA or AA of 3.51, 95% CI 1.19 to 10.3). Comparisons of treatment effects between genotype groups within pharmacotherapy randomisation arms For those receiving active NRT, treatment was more effective in achieving six-month abstinence among individuals with a slow NMR than among those with a normal NMR among NHW and NHB combined participants (normal NMR vs slow NMR: RR 0.54, 95% CI 0.37 to 0.78; n = 2 trials). We found no such differences in treatment effects between genotypes at six months for any of the other biomarkers among individuals who received pharmacotherapy or placebo. Authors' conclusions We did not identify widespread differential treatment effects of pharmacotherapy based on genotype. Some genotype groups within certain ethnic groups may benefit more from NRT or may benefit less from the combination of bupropion with NRT. The reader should interpret these results with caution because none of the statistically significant meta-analyses included more than two trials per genotype comparison, many confidence intervals were wide, and the quality of this evidence (GRADE) was generally moderate. Although we found evidence of superior NRT efficacy for NMR slow versus normal metabolisers, because of the lack of heterogeneity between NMR groups, we cannot conclude that NRT is more effective for slow metabolisers. Access to additional data from multiple trials is needed, particularly for comparisons of different pharmacotherapies.

Overlapping network meta-analyses on the same topic: survey of published studies

Abstract: Background: To assess how common it is for a published network meta-analysis (NMA) to have other published overlapping NMAs, and to evaluate these overlaps.Methods: A total of 88 NMAs of randomized controlled trials evaluating the comparative effectiveness of health interventions were randomly selected. For each of these, we searched for NMAs on the same topic. A random sample of 40 pairs (an index NMA and one of its overlapping NMAs) was selected to assess the overlap in terms of nodes, treatments and references. The topic with the largest number of overlapping NMAs was described in depth.Results: In all, 68 of the 88 index NMAs had at least one overlapping NMA: 77% [95% confidence interval (CI), 69-86%]. We identified 515 pairs of overlapping NMAs. Among the 40 randomly selected pairs, 73% (95% CI, 58-88%) of nodes, 79% (95% CI, 72-86%) of treatments and 48% (95% CI, 37-59%) of references included in the index NMAs were also found in the respective overlapping NMAs. Efficacy of biologics in rheumatoid arthritis had the largest number of overlapping NMAs, with 28 NMAs published between 2003 and 2014. Differences in selection and definition of nodes of treatments resulted in different network geometries. There were also differences in both the direction and the statistical significance of effects.Conclusions: Published NMAs exhibit extensive overlap and potential redundancy. Erratic retrieval of eligible trials, and lack of consensus on the range of interventions to be considered and how they might be merged or split in different nodes, may cause confusion.

A multi-centre, non-inferiority, randomised controlled trial to compare a cervical pessary with a cervical cerclage in the prevention of preterm delivery in women with short cervical length and a history of preterm birth – PC study

Abstract: Background Preterm birth is in quantity and in severity the most important contributor of perinatal morbidity and mortality both in well- and low-resource countries. Cervical pessary and cervical cerclage are both considered as preventive treatments in women at risk for preterm birth. We aim to evaluate whether a cervical pessary can replace cervical cerclage for preventing recurrent preterm birth in women with a prior preterm birth due to cervical insufficiency or in women with a prior preterm birth and a short cervix in the current pregnancy. Methods/design A nationwide open-label multicentre randomised clinical trial will be set up to study women with a singleton pregnancy and a prior preterm birth before 34 weeks of gestation. Women are eligible in case of previous preterm birth based on cervical insufficiency (primary intervention, Discussion The outcome of this study will indicate the effectiveness and the cost-effectiveness of a cervical cerclage and of a cervical pessary. Trial registration Netherlands Trial Registry, NTR 4415 . Date registered: 29th of January 2014.

Influence of cut-off value on prevalence of short cervical length

Abstract: Objective To assess the distribution of cervical length (CL) in a large cohort of asymptomatic low-risk women with singleton pregnancy and no previous preterm birth and to explain the low prevalence of short CL ≤ 30 mm in this cohort. Methods This was a secondary analysis of a multicenter cohort study with an embedded randomized controlled trial (Triple P trial; NTR-2078) on the prevention of preterm birth with progesterone. In the cohort study, CL was measured in asymptomatic low-risk women with singleton pregnancy to investigate its predictive capacity to identify those at increased risk for preterm birth. A short CL was defined by a cut-off value of ≤ 30 mm, based on existing literature. Women with a short CL were subsequently included in a randomized controlled trial evaluating the effect of progesterone, compared with placebo, on preterm birth. In total, 57 centers and 20 234 women participated in the study. Normal distributions for CL were simulated based on the mean and SD of the original data. The distribution of CL was assessed for each individual center and measurements were compared between levels of care: primary (29 ultrasound centers), secondary (21 general hospitals) and tertiary (seven university medical centers) care institutions. Comparison was also performed between centers with low, intermediate and high volume of CL measurements. CL distributions before (n = 12 284 women) and after (n = 7950 women) a national symposium, at which the prevalence of short CL measurements was addressed publicly, were analyzed. Results Between November 2009 and August 2013, 20 234 women had CL measurements, of whom 367 (1.8%) had a short CL. Mean ± SD CL was 44.2 ± 7.8 mm. A ‘dip’ in the distribution of CL measurements between 20 and 30 mm was observed, defined by a ratio of < 50% when comparing the number of measurements in observed and simulated normal distributions. The dip was present in 89% of participating centers. All centers showed a dip in the distribution of measurements ≤ 30 mm when analyzed according to the level of care and volume of measurements. A significant difference was found when comparing the distribution before and after publicly addressing the low prevalence of short CL (1.7% vs 2.0% of measurements were ≤ 30 mm, respectively; P < 0.001). Conclusions A cut-off value of 30 mm for CL was used to include women in a randomized clinical trial that was embedded in a cohort study. We suggest that the use of a predefined cut-off value for a short cervix influences the distribution of the CL measurements. Since the measurement is not blinded, preference of assessors for the control or intervention arms may have introduced selection bias. This might have resulted in fewer measurements around the cut-off value. Other trials using similar designs could benefit from this observation and take precautions to avoid selection bias. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Pessary or Progesterone to Prevent Preterm delivery in women with short cervical length: the Quadruple P randomised controlled trial

Abstract: Preterm birth is in quantity and in severity the most important topic in obstetric care in the developed world. Progestogens and cervical pessaries have been studied as potential preventive treatments with conflicting results. So far, no study has compared both treatments. The Quadruple P study aims to compare the efficacy of vaginal progesterone and cervical pessary in the prevention of adverse perinatal outcome associated with preterm birth in asymptomatic women with a short cervix, in singleton and multiple pregnancies separately. It is a nationwide open-label multicentre randomized clinical trial (RCT) with a superiority design and will be accompanied by an economic analysis. Pregnant women undergoing the routine anomaly scan will be offered cervical length measurement between 18 and 22 weeks in a singleton and at 16–22 weeks in a multiple pregnancy. Women with a short cervix, defined as less than, or equal to 35 mm in a singleton and less than 38 mm in a multiple pregnancy, will be invited to participate in the study. Eligible women will be randomly allocated to receive either progesterone or a cervical pessary. Following randomization, the silicone cervical pessary will be placed during vaginal examination or 200 mg progesterone capsules will be daily self-administered vaginally. Both interventions will be continued until 36 weeks gestation or until delivery, whichever comes first. Primary outcome will be composite adverse perinatal outcome of perinatal mortality and perinatal morbidity including bronchopulmonary dysplasia, intraventricular haemorrhage grade III and IV, periventricular leukomalacia higher than grade I, necrotizing enterocolitis higher than stage I, Retinopathy of prematurity (ROP) or culture proven sepsis. These outcomes will be measured up until 10 weeks after the expected due date. Secondary outcomes will be, among others, time to delivery, preterm birth rate before 28, 32, 34 and 37 weeks, admission to neonatal intensive care unit, maternal morbidity, maternal admission days for threatened preterm labour and costs. This trial will provide evidence on whether vaginal progesterone or a cervical pessary is more effective in decreasing adverse perinatal outcome in both singletons and multiples. Trial registration number: NTR 4414 . Date of registration January 29th 2014.

Why STAN might not be dead.

Abstract: Recently, a meta-analysis, including 26 526 laboring vertex singletons at term, summarized all available level-1 data from six high-quality randomized clinical trials (RCTs) on the use of ST analysis (STAN) during labor as an adjunct to conventional intrapartum fetal heart rate monitoring. The meta-analysis showed that STAN did not improve perinatal outcomes or decrease cesarean deliveries. Nonetheless, there are still reasons to believe STAN may have a role in the future research on intrapartum fetal monitoring. Out of six trials included in the meta-analysis, two included all cephalic singletons in labor, and four enrolled only high-risk pregnant women. This combination of both low- and high-risk populations may have distorted the potential impact of STAN. The test for heterogeneity between both subgroups was found to be statistically significant, indicating that the effect of STAN was different in high-risk women compared to a combination of both low- and high-risk women. Furthermore, the class...

Simulation-based Team Training for Multiprofessional Obstetric Care Teams to Improve Patient Outcome: A Multicentre, Cluster Randomized Controlled Trial

Abstract: S training is considered an important component in medical education. It provides a more effective method for teaching technical skills through practice without risk to the patient. It has also been recommended for obstetric teams as a way to improve team performance and perhaps obstetric outcomes. Criteria for assessing simulation training has included participants’ perceptions of the simulation experience, assessment of knowledge and skills during and after simulation, subsequent changes in clinical practice, and ultimately improvement in patient outcomes. However, data on the effect of simulation training on patient outcomes has been limited. This study looked at the effect of a 1-day simulation-based training course for obstetric teams on the rate of patient complications over a 1-year period. This was a nonblinded, multicenter, cluster randomized controlled trial performed between 2009 and 2011. Obstetric units in the Netherlands who were not already participating in multidisciplinary team training were eligible to participate in the study. Participating obstetric units were randomized to the intervention group that underwent simulation-based team training or the control group. The simulation training focused on teamwork skills, including crew resource management and communication during emergency situations. The 1-day, 8-hour training session took place at a single medical simulation center that included rooms furnished as delivery rooms. The entire multidisciplinary standard obstetric team from units assigned to the intervention group participated in the simulation training. These teams included an obstetrician, obstetric resident or secondary-level midwife, and obstetric nurse. Anesthesiologists are not considered part of the standard obstetric team in the Netherlands and did not participate in the simulation training. The course consisted of 5 cases of increasing complexities. Debriefings were conducted with the team after each scenario. Assessment of patient outcomes at the participating institutions was obtained by collecting data from patients with singleton pregnancies beyond 24 weeks gestation who delivered during the 1-year period after simulation training. The primary outcome studied was a composite of the following adverse outcomes: low Apgar score, severe postpartum hemorrhage (PPH), trauma secondary to shoulder dystocia, eclampsia, and hypoxic-ischemic encephalopathy. Secondary outcomes tracked were perinatal and maternal mortality. A total of 24 obstetric units participated in the study. For both the simulation and control groups, 5 were teaching units and 7 were nonteaching units. Data were collected from 14,500 patients in the intervention group and 14,157 patients in the control group. The primary composite outcome of obstetric complications did not differ significantly between the intervention and control groups, with a rate of 2.0% for the intervention group and 2.1% for the control group [odds ratio (OR), 1.0; 95% confidence interval (CI), 0.80-1.3]. There were differences, however, between groups for some of the component outcomes included in the primary composite outcome. Trauma due to shoulder dystocia was lower for the intervention group compared to the control group (0.16% vs. 0.25%; OR, 0.50; 95% CI, 0.25-0.99) while treatment for severe PPH was greater for the intervention group than the control group (0.28% vs. 0.13%; OR, 2.2; 95% CI, 1.2-3.9). There were no significant differences between groups for the other components of the primary outcome. No differences in perinatal and maternal mortality were found. In conclusion, no improvement in obstetric complication rates was found among obstetric units that participated in simulation-based team training compared with those that did not participate. Previous studies have shown simulation training to improve teamwork and medical skills. However, similar results from other studies showing no significant change in patient outcomes after simulation training have been published. The investigators proposed several factors that potentially influenced the results. These included the short duration of the simulation course, a training focus on teamwork skills but not medical skills, and the off-site location of the simulation center. Importantly, the lack of an effect from simulation training on patient outcomes might have been affected by not including in the simulation training others that could be considered important members of the obstetric care team. This would include anesthesiologists and primary care midwives, who initially care for > 50% of laboring Dutch parturients but ultimately transfer the care of 44% of their patients to a secondary team due to development of obstetric complications.

Maintenance Tocolysis With Nifedipine in Threatened Preterm Labour: 2-Year Follow-up of the Offspring in the APOSTEL II Trial

Abstract: (BJOG 2016;123(7):1107–1114)Preterm birth is associated with an increased risk of perinatal morbidity and mortality, with the earlier the birth the greater the risk Some of the complications resulting from preterm delivery lead to impairments with long-term consequences Hence delivery postponemen

Methods for Evaluating Medical Tests and Biomarkers

Abstract: Joris de Groot, Christiana Naaktgeboren, Hans Reitsma, Carl Moons Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands Correspondence: Joris de Groot (j.degroot-17@umcutrecht.nl) A major contributor to the rising problem of overdiagnosis, with the subsequent risk of overtreatment, is the development of highly sensitive diagnostic technologies that challenge and sometimes expand prevailing disease definitions. Although the value of such new technology might be that it identifies new, milder, earlier or even other abnormalities, it is uncertain whether these “abnormalities” provide the same diagnostic and prognostic information, or require the same treatment as the original targeted disease. It is often unclear which of the newly detected abnormalities are benign and how many people might be diagnosed and treated unnecessarily as a result of widespread introduction of the new test. Failure to investigate the clinical relevance of broadening disease definitions which include these newly detected abnormalities may therefore lead to overdiagnosis and overtreatment. Spiral CT used in diagnosing pulmonary embolism, detecting small subsegmental embolisms, has been mentioned as an example of such situation. On-going technological advancements in medicine will only further increase the development of new diagnostic technologies that challenge existing disease definitions. We show why traditional cross-sectional diagnostic accuracy studies are insufficient to evaluate such new tests and how methodology for assessing their performance should catch up and keep pace with present-day technological developments. It is crucial to improve data analysis and presentation of current diagnostic studies, to make better use of existing data, or ultimately perform test-treatment trials to answer the question whether introduction of a new high sensitive test will in fact improve patient relevant outcomes, or rather induce overdiagnosis and overtreatment.

Prospective Risk of Stillbirth and Neonatal Complications in Twin Pregnancies : Systematic Review and Meta-analysis

Abstract: Twin pregnancies are at increased risk of stillbirth. Uncomplicated twin pregnancies are commonly delivered earlier to prevent stillbirth; however, there is a risk of neonatal complications associated with being born prior to 39 weeks’ gestation. The optimal gestational age for delivery in twin pregnancies is unknown and likely varies by chorionicity. The present study aimed to determine the prospective risk of stillbirth in women with uncomplicated monochorionic and dichorionic twin pregnancies, and neonatal mortality risks, when delivered beyond 34 weeks of gestation. Data on twin pregnancies that reported rates of stillbirth were obtained from MEDLINE, EMBASE, and Cochrane Library. Separate analyses for risks of stillbirth and neonatal death in monochorionic and dichorionic twin pregnancies were undertaken from 34 weeks’ gestation and further and early preterm (<34 weeks’) gestation. The risk of neonatal outcomes was estimated every week by multilevel random-effects logistic regression models, and point estimates of the risk of each event were obtained by the gestational period with its corresponding 95% confidence interval (CI). Results for the dichorionic twin pregnancies indicated that the prospective risk of stillbirth was 1.2 per 1000 pregnancies (95% CI, 0.7–1.8) at 34 weeks, with the related risk of neonatal death of 6.7 per 1000 pregnancies (95% CI, 3.3–13.5). The stillbirth risk was found to be significantly lower than the risk of neonatal death at 34 weeks (risk difference, -5.8/1000) and 35 weeks (-5.1/1000). The perinatal risks were balanced at 37 + 0–6 weeks (1.2/1000, -1.3 to 3.6/1000), beyond which the risks of stillbirth (10.6/1000) outweighed the risk of neonatal death significantly (1.5/1000) from delivery at the same gestational age (risk difference, 8.8/1000, 3.6–14). The prospective risk of stillbirth and neonatal mortality rates in monochorionic pregnancies at 34 weeks’ gestation were 0.9/1000 (95% CI, 0.1–3.4) and 12.1/1000 (95% CI, 4.2–34.3), respectively. The risks of neonatal death were greater than the risks of stillbirth at 34 weeks (risk difference, -15.6/1000) and 35 weeks (risk difference, -2.4/1000). A trend in which the risk of stillbirth (9.6/1000; 95% CI, 3.9–19.7) was higher than the risk of neonatal death (3.6/1000; 95% CI, 1.2–11.1) with a risk difference of 2.5/1000 (95% CI, -12.4 to 17.4/1000; I2 = 0%) was observed after 36 + 0–6 weeks. The study concluded that delivery should be considered at 37 weeks of gestation in uncomplicated dichorionic twin pregnancies and at 36 weeks of gestation in monochorionic pregnancies to reduce the incidence of perinatal deaths.

Erratum to: Methods for evaluating medical tests and biomarkers.

Abstract: [This corrects the article DOI: 10.1186/s41512-016-0001-y.].