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Design A retrospective study.Cohort selection Inclusion criteria included: participants of any age who had completed their fixed orthodontic treatment on both arches and were treated by the same orthodontist in their private practice; had bonded retainers for five years, which were placed immediately after the orthodontic treatment in both arches; had one of three types of bonded retainers (0.026 × 0.010 inch Bond-A-Braid, 0.038 × 0.016 inch Ortho-FlexTech and Reliance Retainium Superior Brand Lingual Retainer Wire); had a final overbite of 2-4 mm after the completion of orthodontic treatment. Subjects who got their retainers changed, repaired or removed before five years, and syndromic patients, were excluded from the study.Data analysis The participants who agreed to contribute to the study and came for the final clinical examination were assessed for the retention status and the periodontal/gingival indies. Retention and retainer status: unwanted tooth movements and time and type of retainer failure. Periodontal/gingival indies: maximum pocket depth (PD) from the lingual side for the retained teeth and bleeding on probing (BOP). The authors performed a series of analyses to compare the orthodontic retainers regarding several outcomes and demographic variables. Briefly, the authors compared the orthodontic retainers concerning: i) age and treatment duration using analysis of variance (since the data were found to be normally distributed based on the Kolmogorov-Smirnov test); ii) demographic variables and BOP using several Chi-square tests; iii) PD via the Kruskal-Wallis test; and iv) survival rate through a Cox regression model alongside log-rank test.Results In total, 118 patients were included in this study, of which, 90 were women and 28 were men, with an average age of 22.34 ± 6.44 years. There was no statistically significant difference in the survival rate between the three types of retainers or between men and women. Likewise, there was no statistically significant difference in survival rate between the different age groups for the maxilla and mandible. Different maximum and minimum failure rates were observed between teeth in the maxilla and the mandible in the three retainers' group.Conclusions No difference was found between the three types of bonded retainers in regard to the survival rate and periodontal indices.

Systematic reviews with meta-analyses are powerful tools that can answer research questions based on data from published studies. Ideally, all relevant data is directly available in the text or tables, but often it is only presented in graphs. In those cases, the data can be extracted from graphs, but this potentially introduces errors. Here, we investigate to what extent the extracted outcome and error values differ from the original data and if these differences could affect the results of a meta-analysis. Six extractors extracted 36 outcome values and corresponding errors from 22 articles. Differences between extractors were compared using overall concordance correlation coefficients (OCCC), differences between the original and extracted data were compared using concordance correlation coefficients (CCC). To test the possible influence on meta-analyses, random-effects meta-analyses on mean difference comparing original and extracted data were performed. The OCCCs and CCCs were high for both outcome values and errors, CCCs were >0.99 for the outcome and >0.92 for errors. The meta-analyses showed that the overall effect on outcome was very small (median: 0.025, interquartile range: 0.016-0.046). Therefore, data extraction from graphs is a good method to harvest data if it is not provided in the text or tables, and the original authors cannot provide the data.

Meta-analysis is usually performed using aggregate data. Aggregate data refer to the summary of individual participant data (IPD) on the investigated outcomes and related characteristics obtained from the trial reports. In the case of binary outcome data, the aggregate data include the number of participants who experienced the event (eg, bond failures per treatment group) from the total randomized in the trial. For continuous outcomes, such as overjet, intercanine, and intermolar width or space closure in millimeters, the researcher extracts the number of participants, the mean and standard deviation of the outcome measured in each trial arm. In terms of characteristics, aggregate data can include the summary of participant- and clinical-related characteristics, such as the mean age, gender distribution across arms, and the mean follow-up period. Although aggregate data allow for a straightforward analysis, they cannot always uncover the true associations between treatment effects and characteristics. Over time, the well-documented limitations of aggregate data analysis have initiated a paradigm shift for collecting and re-analyzing IPD, whenever possible, after the principles and procedures of conventional systematic reviews.1,2 Systematic reviews of IPD have gained popularity in the therapeutic, diagnostic, and prognostic research in numerous health care fields.3

Objectives: To investigate the implications of addressing informative missing binary outcome data (MOD) on network meta-analysis (NMA) estimates while applying the missing at random (MAR) assumption under different prior structures of the missingness parameter. Methods: In three motivating examples, we compared six different prior structures of the informative missingness odds ratio (IMOR) parameter in logarithmic scale under pattern-mixture and selection models. Then, we simulated 1000 triangle networks of two-arm trials assuming informative MOD related to interventions. We extended the Bayesian random-effects NMA model for binary outcomes and node-splitting approach to incorporate these 12 models in total. With interval plots, we illustrated the posterior distribution of log OR, common between-trial variance (τ2), inconsistency factor and probability of being best per intervention under each model. Results: All models gave similar point estimates for all NMA estimates regardless of simulation scenario. For moderate and large MOD, intervention-specific prior structure of log IMOR led to larger posterior standard deviation of log ORs compared to trial-specific and common-within-network prior structures. Hierarchical prior structure led to slightly more precise τ2 compared to identical prior structure, particularly for moderate inconsistency and large MOD. Pattern-mixture and selection models agreed for all NMA estimates. Conclusions: Analyzing informative MOD assuming MAR with different prior structures of log IMOR affected mainly the precision of NMA estimates. Reviewers should decide in advance on the prior structure of log IMOR that best aligns with the condition and interventions investigated.

Missing participant outcome data (MOD) are ubiquitous in clinical trials and may threaten the validity of the results. The risk of bias associated with MOD is carried over to the meta-analysis by including clinical trials with participant losses.1 In this section, we discuss MOD, and we present common statistical methods to address MOD in a pairwise metaanalysis. Despite their conceptual and statistical shortcomings, these methods have prevailed in the published systematic reviews for their simplicity.

Appropriate handling of aggregate missing outcome data is necessary to minimise bias in the conclusions of systematic reviews. The two-stage pattern-mixture model has been already proposed to address aggregate missing continuous outcome data. While this approach is more proper compared with the exclusion of missing continuous outcome data and simple imputation methods, it does not offer flexible modelling of missing continuous outcome data to investigate their implications on the conclusions thoroughly. Therefore, we propose a one-stage pattern-mixture model approach under the Bayesian framework to address missing continuous outcome data in a network of interventions and gain knowledge about the missingness process in different trials and interventions. We extend the hierarchical network meta-analysis model for one aggregate continuous outcome to incorporate a missingness parameter that measures the departure from the missing at random assumption. We consider various effect size estimates for continuous data, and two informative missingness parameters, the informative missingness difference of means and the informative missingness ratio of means. We incorporate our prior belief about the missingness parameters while allowing for several possibilities of prior structures to account for the fact that the missingness process may differ in the network. The method is exemplified in two networks from published reviews comprising a different amount of missing continuous outcome data.

BACKGROUND Systematic reviews have established the short-term improvements of periodontal regenerative/reconstructive procedures compared to conventional surgical treatment in intrabony defects. However, a hierarchy of periodontal regenerative/reconstructive procedures regarding the medium- to long-term results of treatment does not exist. AIM To systematically assess the literature to answer the focused question "In periodontitis patients with intrabony defects, what are the medium- and long-term benefits of periodontal regenerative/reconstructive procedures compared with open flap debridement (OFD), in terms of clinical and/or radiographic outcome parameters and tooth retention?". MATERIAL & METHODS Randomized controlled clinical trials (RCTs), reporting on clinical and/or radiographic outcome parameters of periodontal regenerative/reconstructive procedures ���3��years post-operatively, were systematically assessed. Clinical [residual probing pocket depth (PD) and clinical attachment level (CAL) gain, tooth loss] and radiographic [residual defect depth (RDD), bone gain (RBL)] outcome parameters were assessed. Descriptive statistics were calculated, and Bayesian random-effects network meta-analyses (NMA) were performed where possible. RESULTS Thirty RCTs, presenting data 3 to 20��years after treatment with grafting, GTR, EMD, as monotherapies, combinations thereof, and/or adjunctive use of blood-derived growth factor constructs or with OFD only, were included. NMA based on 21 RCTs showed that OFD was clearly the least efficacious treatment; regenerative/reconstructive treatments resulted in significantly shallower residual PD in 4 out 8 comparisons [range of mean differences (MD): -2.37 to -0.60��mm] and larger CAL gain in 6 out 8 comparisons (range of MD: 1.26 to 2.66��mm), and combination approaches appeared as the most efficacious. Tooth loss after regenerative/reconstructive treatment was less frequent (0.4%) compared to OFD (2.8%), but the evidence was sparse. There were only sparse radiographic data not allowing any relevant comparisons. CONCLUSION Periodontal regenerative/reconstructive therapy in intrabony defects results, in general, in shallower residual PD and larger CAL gain compared with OFD, translating in high rates of tooth survival, on a medium (3-5��years) to long-term basis (5-20��years). Combination approaches appear, in general, more efficacious compared to monotherapy in terms of shallower residual PD and larger CAL gain. A clear hierarchy could, however, not be established due to limited evidence.

Conducting sensitivity analyses is an integral part of the systematic review process to explore the robustness of results derived from the primary analysis. When the primary analysis results can be sensitive to assumptions concerning a model's parameters (e.g., missingness mechanism to be missing at random), sensitivity analyses become necessary. However, what can be concluded from sensitivity analyses is not always clear. For instance, in a pairwise meta-analysis (PMA) and network meta-analysis (NMA), conducting sensitivity analyses usually boils down to examining how 'similar' the estimated treatment effects are from different re-analyses to the primary analysis or placing undue emphasis on the statistical significance. To establish objective decision rules regarding the robustness of the primary analysis results, we propose an intuitive index, which uses the whole distribution of the estimated treatment effects under the primary and alternative re-analyses. This novel index is compared to an objective threshold to infer the presence or lack of robustness. In the case of missing outcome data, we additionally propose a graph that contrasts the primary analysis results to those of alternative scenarios about the missingness mechanism in the compared arms. When robustness is questioned according to the proposed index, the suggested graph can demystify the scenarios responsible for producing inconsistent results to the primary analysis. The proposed decision framework is immediately applicable to a broad set of sensitivity analyses in PMA and NMA. We illustrate our framework in the context of missing outcome data in both PMA and NMA using published systematic reviews.

Background Atopic dermatitis (AD) is an inflammatory chronic condition that affects the skin of children and adults and has an important impact on the quality of life. Treatments for AD are based on environmental controls, topical and systemic therapies, and allergen-specific immunotherapy (AIT). However, it remains unclear the effectiveness and adverse events of AIT and all conventional topical treatments compared with placebo and each other for AD. Methods We will search five electronic databases [Central Cochrane register of controlled trials (CENTRAL), MEDLINE, EMBASE, CINAHL, and LILACS] from inception until November 2019 with no language restriction, and we will include experimental studies [randomized controlled trials (RCTs), and quasi-RCTs]. The primary outcome is global and specific skin symptoms assessment. Secondary outcomes are hospital length of stay, quality of life, and adverse events. Reviewers independently will extract data from the studies that meet our inclusion criteria and will assess the risk of bias of individual primary studies. We will conduct random effects pairwise meta-analyses for the observed pairwise comparisons with at least two trials. Then, we will perform random-effects Bayesian network meta-analysis (NMA) to obtain treatment effects for all possible comparisons and to provide a hierarchy of all interventions for each outcome. Possible incoherence between direct and indirect sources of evidence will be investigated locally (if possible) and globally. To investigate sources of statistical heterogeneity, we will perform a series of meta-regression analyses based on pre-specified important effect modifiers. Two authors will appraise the certainty of the evidence for each outcome applying the GRADE’s framework for NMA. Discussion The findings of this systematic review will shed the light on the effectiveness and adverse events of all possible comparisons for treating AD and on the quality of the collated evidence for recommendations. It will also provide critical information to health care professionals to comprehend and manage this disease at different age stages, treatment type, duration, and severity of atopic dermatitis. Systematic review registration PROSPERO Protocol ID CRD42019147106

Background Trials with binary outcomes can be synthesised using within-trial exact likelihood or approximate normal likelihood in one-stage or two-stage approaches, respectively. The performance of the one-stage and the two-stage approaches has been documented extensively in the literature. However, little is known about how these approaches behave in the presence of missing outcome data (MOD), which are ubiquitous in clinical trials. In this work, we compare the one-stage versus two-stage approach via a pattern-mixture model in the network meta-analysis using Bayesian methods to handle MOD appropriately. Methods We used 29 published networks to empirically compare the two approaches concerning the relative treatment effects of several competing interventions and the between-trial variance (τ2), while considering the extent and level of balance of MOD in the included trials. We additionally conducted a simulation study to compare the competing approaches regarding the bias and width of the 95% credible interval of the (summary) log odds ratios (OR) and τ2 in the presence of moderate and large MOD. Results The empirical study did not reveal any systematic bias between the compared approaches regarding the log OR, but showed systematically larger uncertainty around the log OR under the one-stage approach for networks with at least one small trial or low event risk and moderate MOD. For these networks, the simulation study revealed that the bias in log OR for comparisons with the reference intervention in the network was relatively higher in the two-stage approach. Contrariwise, the bias in log OR for the remaining comparisons was relatively higher in the one-stage approach. Overall, bias increased for large MOD. For these networks, the empirical results revealed slightly higher τ2 estimates under the one-stage approach irrespective of the extent of MOD. The one-stage approach also led to less precise log OR and τ2 when compared with the two-stage approach for large MOD. Conclusions Due to considerable bias in the log ORs overall, especially for large MOD, none of the competing approaches was superior. Until a more competent model is developed, the researchers may prefer the one-stage approach to handle MOD, while acknowledging its limitations.

Objectives The objectives of this study were to elaborate on the conceptual evaluation of transitivity assumption in the context of binary missing participant outcome data (MOD) in network meta-analysis (NMA) and to emphasize on the importance of statistical modeling as a mean to address MOD. Study Design and Setting We designate the notion of transitivity assumption in the context of binary MOD and indicate scenarios that compromise transitivity in complex networks. We propose a modification of these scenarios that preserves transitivity assumption. Using a published NMA, we indicate the implications of excluding or imputing, rather than modeling MOD, on NMA findings. Results Arm-specific scenarios for MOD, as commonly applied in conventional meta-analysis, compromise the validity of transitivity assumption in complex networks. The motivating example reveals that imputation of those scenarios yields estimates in the opposite direction for the basic parameters with narrower credible intervals and inflates between-trial variance. Contrariwise, modeling MOD after modification of the scenarios yields robust estimates for the basic parameters but wider credible intervals and reduces between-trial variance. Conclusion Application of arm-specific scenarios for binary MOD requires modification in complex networks to ensure valid transitivity assumption. Analysts should model, rather than exclude or impute MOD, to provide bias-adjusted results.

Objectives To evaluate microstructural cerebral changes in children with neurofibromatosis type 1 (NF1) based on T2 relaxation time measurements at 3Tesla. Methods From our dataset of pediatric MRI examinations at 3T 19 pediatric NF1 patients (1.9–14.3 years of age, 9 girls, 10 boys) were retrospectively selected and compared with the previously published group of 44 healthy children (0–16 years of age). MRI examination included a triple echo TSE sequence as basis for T2 maps. T2 relaxation times were measured in 37 brain regions. Results Compared with healthy controls, T2 relaxation times had the tendency to be increased by 1.01% (GM) to 11.85% (dentate nucleus) for NF1 patients. Only in posterior limb of the internal capsule and parietooccipital white matter values were reduced. No differences were observed between both hemispheres. Overall, no strong evidence supporting a difference between NF1 patients with and without optic glioma or with normal and impaired neuropsychological development was observed. Conclusions Using T2 relaxation times it was possible to describe measurable microstructural differences in multiple brain regions between NF1 patients and healthy children regardless of whether signal abnormalities were visible on conventional images.

Objective To examine age-related changes in T2 relaxation times during infancy and childhood in order to assess T2 values obtained from routine MRI as a biomarker. Methods From our pool of clinical pediatric MRI examinations at 3 T all patients with normal conventional MRI scans were retrospectively selected. Depending on their clinical findings the identified 99 patients (0–199 months) were divided into 43 healthy controls and 56 diseased children with various clinical abnormalities (developmental delay, epilepsy, prematurity, and deafness). T2 maps based on routinely performed triple echo turbo spin echo sequences were created. T2 values were measured in 22 brain regions to determine age-related changes. We also investigated whether such changes differ between healthy and diseased children. Results Age significantly reduced T2 relaxation times across all regions (p Conclusions Using T2 maps based on clinical MRI data we could determine age-related T2 relaxation times in 22 brain regions during infancy and childhood. Our data have relevance for future investigator independent T2 relaxation time measurements in determining whether T2 values are within the normal range or should be considered as potentially pathologic.

The purpose of this study was to examine age-related, infratentorial changes in T2 relaxation times during infancy and childhood using routine MRI data at 3 Tesla. One hundred patients (0–199 months) without signal abnormalities on conventional MRI were retrospectively selected from our pool of pediatric MRI examinations. T2 maps based on our routinely acquired triple-echo turbo spin-echo (TSE) sequence were created. Based on their clinical symptoms, the children were divided into 43 controls and 57 diseased children with different clinical diseases. T2 relaxation times were measured in 15 infratentorial brain regions (medullary pyramid, ventral and dorsal pons, middle cerebellar peduncle, dentate nucleus, medial and lateral cerebellar hemisphere each on both sides, and in the cerebellar vermis) investigating age-related changes. Secondly, this study examined whether those changes in T2 values differed between healthy and diseased children. Age significantly reduced T2 relaxation time in all infratentorial brain regions (p 0.05) apart from the dentate nucleus and cerebellar hemispheres in terms of rapid decline (larger in controls) and the right dorsal pons and left pyramid in terms of slow decline (larger in diseased children). In both groups, the later slow decline was almost negligible. Using T2 maps, it was possible to determine age-related T2 relaxation times in the different infratentorial brain regions in this preliminary study. Between neurologically healthy controls and diseased children, no significant differences in T2 relaxation times could be found overall in the studied regions.

Humanized mice engrafted with human hematopoietic stem cells and developing functional human T-cell adaptive responses are in critical demand to test human-specific therapeutics. We previously showed that humanized mice immunized with long-lived induced–dendritic cells loaded with the pp65 viral antigen (iDCpp65) exhibited a faster development and maturation of T cells. Herein, we evaluated these effects in a long-term (36 weeks) nonclinical model using two stem cell donors to assess efficacy and safety. Relative to baseline, iDCpp65 immunization boosted the output of effector memory CD4 + T cells in peripheral blood and lymph nodes. No weight loss, human malignancies, or systemic graft- versus -host (GVH) disease were observed. However, for one reconstitution cohort, some mice immunized with iDCpp65 showed GVH-like signs on the skin. Histopathology analyses of the inflamed skin revealed intrafollicular and perifollicular human CD4 + cells near F4/80 + mouse macrophages around hair follicles. In spleen, CD4 + cells formed large clusters surrounded by mouse macrophages. In plasma, high levels of human T helper 2–type inflammatory cytokines were detectable, which activated in vitro the STAT5 pathway of murine macrophages. Despite this inflammatory pattern, human CD8 + T cells from mice with GVH reacted against the pp65 antigen in vitro . These results uncover a dynamic cross-species interaction between human memory T cells and mouse macrophages in the skin and lymphatic tissues of humanized mice.

Brain metastases in patients with breast cancer are associated with a poor survival rate. A small number of studies have challenged this premise, suggesting that survival times following brain metastasis differ significantly between breast cancer subtypes. In the current study, overall survival (OS), brain metastases-free survival (BMFS) and survival following brain metastases (SFBM) were found to be associated with the intrinsic breast cancer subtype. A total of 1,147 patients with invasive breast cancer who were treated at the Hannover Medical School between January 2004 and December 2010 were included, from which 54 patients with brain metastases were identified. The Kaplan-Meier method or Cox regression analyses were performed for analysis of survival. OS was found to differ significantly between breast cancer subtypes: OS was significantly shorter in patients with triple-negative (TN) cancer compared with patients with human epidermal growth factor receptor (HER2)-enriched tumors (P

The goal of a meta-analysis is not only to synthesize the information of selected studies, estimate the summary effect size, and infer whether and how much the compared interventions differ in terms of their effectiveness but also to assess whether there is evidence of (statistical) heterogeneity in the true effect sizes, the magnitude of this heterogeneity, and its implications on the interpretation of the results. The term heterogeneity refers to the dispersion of the true effect sizes across the studies included in a meta-analysis.1 In this article, we address the importance of statistical heterogeneity, and we present various tools that quantify the magnitude of heterogeneity and tools that signify the presence of heterogeneity in a random-effects metaanalysis model, known as measures of heterogeneity. Statistical heterogeneity should not be confused with clinical heterogeneity, a related concept that refers to the heterogeneity of the included studies in terms of the characteristics of the included participants, the applied treatments, and the measured outcomes.

Meta-regression is simply the extension of the regression analysis. Whereas in the regression analysis, the outcome and the covariates are measured for each subject, in meta-regression, the outcome and the covariates are measured on the level of the study. Because studies differ at least in the sample size, we need to assign a weight in each study under a specific model (fixed-effect or random-effects model) before implementing a meta-regression analysis. Weight assignment is not addressed in a regression analysis, because we study subjects. The differences between the regression and the meta-regression analysis are obvious, but the goal is the same: to assess the association between an outcome and one or more covariates.

A meta-analysis, a statistical combination of data from selected studies, is implemented by choosing a priori between 2 popular statistical models: fixed-effect and random-effects models.1 The choice of the appropriate model for the analysis is critical to ensure the credibility of the results and depends on both the goals of the analysis and the assumptions of the models.1 In this section, we introduce these 2 models, describe how to perform a meta-analysis under these models, and apply a real-data example from a published systematic review.

BACKGROUND: In children, functional daytime urinary incontinence is the term used to describe any leakage of urine while awake that is not the result of a known underlying neurological or congenital anatomic cause (such as conditions or injuries that affect the nerves that control the bladder or problems with the way the urinary system is formed). It can result in practical difficulties for both the child and their family and can have detrimental effects on a child’s well‐being, education and social engagement. OBJECTIVES: To assess the effects of conservative interventions for treating functional daytime urinary incontinence in children. SEARCH METHODS: We searched the Cochrane Incontinence Specialised Register, which contains studies identified from CENTRAL, MEDLINE, MEDLINE In‐Process, MEDLINE Epub Ahead of Print, CINAHL, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings (searched 11 September 2018). We also searched Chinese language bibliographic databases: Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), and Wanfang. No language restrictions were imposed. SELECTION CRITERIA: We included randomised controlled trials (RCTs), quasi‐randomised, multi‐arm studies, cross‐over studies and cluster‐randomised studies that included children aged between 5 and 18 years with functional daytime urinary incontinence. DATA COLLECTION AND ANALYSIS: Two review authors independently screened records and determined the eligibility of studies for inclusion according to predefined criteria. Where data from the study were not provided, we contacted the study authors to request further information. Two review authors assessed risk of bias and processed included study data as described in the Cochrane Handbook for Systematic Reviews of Interventions. Where meta‐analysis was possible, we applied random‐effects meta‐analysis using the Mantel‐Haenszel method for dichotomous outcomes. MAIN RESULTS: The review included 27 RCTs involving 1803 children. Of these, six were multi‐arm and one was also a cross‐over study. Most studies were small, with numbers randomised ranging from 16 to 202. A total of 19 studies were at high risk of bias for at least one domain. Few studies reported data suitable for pooling due to heterogeneity in interventions, outcomes and measurements. Individual conservative interventions (lifestyle, behavioural or physical) versus no treatment Transcutaneous electrical nerve stimulation (TENS) versus sham (placebo) TENS. More children receiving active TENS may achieve continence (risk ratio (RR) 4.89, 95% confidence interval (CI) 1.68 to 14.21; 3 studies; n = 93; low‐certainty evidence). One individual conservative intervention versus another individual or combined conservative intervention Pelvic floor muscle training (PFMT) with urotherapy versus urotherapy alone. We are uncertain whether more children receiving PFMT with urotherapy achieve continence (RR 2.36, 95% CI 0.65 to 8.53, 95% CI 25 to 100; 3 studies; n = 91; very low‐certainty evidence). Voiding education with uroflowmetry feedback and urotherapy versus urotherapy alone. Slightly more children receiving voiding education with uroflow feedback and urotherapy may achieve continence (RR 1.13, 95% CI 0.87 to 1.45; 3 studies; n = 151; low‐certainty evidence). Urotherapy with timer watch versus urotherapy alone. We are uncertain whether urotherapy plus timer watch increases the number of children achieving continence compared to urotherapy alone (RR 1.42, 95% CI 1.12 to 1.80; 1 study; n = 58; very low‐certainty evidence). Combined conservative interventions versus other combined conservative interventions TENS and standard urotherapy versus PFMT with electromyographic biofeedback and standard urotherapy. We are uncertain whether there is any evidence of a difference between treatment groups in the proportions of children achieving continence (RR 1.11, 95% CI 0.73 to 1.68; 1 study; n = 78; very low‐certainty evidence). PFMT with electromyography biofeedback and standard urotherapy versus PFMT without feedback but with standard urotherapy. We are uncertain whether there is any evidence of a difference between treatment groups in the proportions of children achieving continence (RR 1.05, 95% CI 0.72 to 1.52; 1 study; n = 41; very low‐certainty evidence). Individual conservative interventions versus non‐conservative interventions (pharmacological or invasive, combined or not with any conservative interventions) PFMT versus anticholinergics. We are uncertain whether more children receiving PFMT than anticholinergics achieve continence (RR 1.92, 95% CI 1.17 to 3.15; equivalent to an increase from 33 to 64 per 100 children; 2 studies; n = 86; very low‐certainty evidence). TENS versus anticholinergics. We are uncertain whether there was any evidence of a difference between treatment groups in the proportions of children achieving continence (RR 0.81, 95% CI 0.05 to 12.50; 2 studies; n = 72; very low‐certainty evidence). Combined conservative interventions versus non‐conservative interventions (pharmacological or invasive, combined or not with any conservative interventions) Voiding education with uroflowmetry feedback versus anticholinergics. We are uncertain whether there was any evidence of a difference between treatment groups in the proportion of children achieving continence (RR 1.02, 95% CI 0.58 to 1.78; 1 study; n = 64; very low‐certainty evidence). AUTHORS' CONCLUSIONS: The review found little reliable evidence that can help affected children, their carers and the clinicians working with them to make evidence‐based treatment decisions. In this scenario, the clinical experience of individual clinicians and the support of carers may be the most valuable resources. More well‐designed research, with well‐defined interventions and consistent outcome measurement, is needed.

Background: Missing participant outcome data (MOD) are ubiquitous in systematic reviews as they invade from the inclusion of clinical trials with reported participant losses. There are available strategies to address aggregated MOD while considering the missing at random (MAR) assumption as a starting[for full text, please go to the a.m. URL], 64. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e.V. (GMDS)

OBJECTIVES The primary objective of this study was to examine the association between the first assessed cervical dilatation in a labourward and the use of oxytocin augmentation during labour. Further analysis was performed by examining the actual stage of labour at the point oxytocin was first administered to those women. DESIGN Retrospective cohort study with the data collected from the medical records of the hospital. SETTING University Hospital Bern, Switzerland PARTICIPANTS: 1933 term nulliparous and multiparous women with a singleton pregnancy giving birth during the period June 2013 and May 2017, representing Robson groups 1 and 3. MEASUREMENTS AND FINDINGS Descriptive statistics and multivariable logistic regression models were performed. It was found that for the entire process of labour, nulliparous and multiparous women (n = 1933) with a first cervical dilatation of 5 or more cm were less likely to be augmented with oxytocin (OR 0.64, 95% CI 0.46; 0.88 and OR 0.56, 95% CI 0.38; 0.82, respectively) compared to women with a first cervical dilatation of less than 5 cm. Out of these augmented women (n = 746) having a first cervical dilatation of 5 or more cm, they had a lower likelihood of being augmented during the first stage of labour compared to women with a first cervical dilatation of less than 5 cm (OR 0.45, 95% CI 0.29; 0.7 for nulliparae and OR 0.32, 95% CI 0.16; 0.6 for multiparae). Additionally, it was observed that other factors contributed to the application of oxytocin. One such example was that epidural analgesia was associated with a high risk of oxytocin augmentation in nulliparae (OR 13.88, 95% CI 9.29; 20.74) and multiparae (OR 15.52, 95% CI 9.94; 24.22). The application of oxytocin was also found to affect the caesarean section rate in nulliparous and multiparous women as it was 20% and 13% respectively for those with oxytocin versus 13% and 4% respectively for those without oxytocin. KEY CONCLUSIONS Early admission to the labourward is associated with an increased use of oxytocin to augment labour, particularly, during the first stage of labour. Epidural analgesia is a main predictor for oxytocin augmentation in nulliparous and multiparous women. IMPLICATIONS FOR PRACTICE Pregnant women warrant more appropriate support during early labour, avoiding early maternal exhaustion and excessive obstetrical interventions.

Background To provide empirical evidence about prevalence, reporting and handling of missing outcome data in systematic reviews with network meta-analysis and acknowledgement of their impact on the conclusions. Methods We conducted a systematic survey including all published systematic reviews of randomized controlled trials comparing at least three interventions from January 1, 2009 until March 31, 2017. Results We retrieved 387 systematic reviews with network meta-analysis. Description of missing outcome data was available in 63 reviews. Intention-to-treat analysis was the most prevalent method (71%), followed by missing outcome data investigated as secondary outcome (e.g., acceptability) (40%). Bias due to missing outcome data was evaluated in half the reviews with explicit judgments in 18 (10%) reviews. Only 88 reviews interpreted their results acknowledging the implications of missing outcome data and mostly using the network meta-analysis results on missing outcome data as secondary outcome. We were unable to judge the actual strategy applied to deal with missing outcome data in 65% of the reviews due to insufficient information. Six percent of network meta-analyses were re-analyzed in sensitivity analysis considering missing outcome data, while 4% explicitly justified the strategy for dealing with missing outcome data. Conclusions The description and handling of missing outcome data as well as the acknowledgment of their implications for the conclusions from network meta-analysis are deemed underreported. Electronic supplementary material The online version of this article (10.1186/s12874-018-0576-9) contains supplementary material, which is available to authorized users.