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Objectives: A prospective parallel cohort trial was conducted to compare outcomes of patients treated with maxillary protraction vs LeFort 1 maxillary advancement surgery.Setting and Sample Population: The primary site for the clinical trial is Children's Hospital Los Angeles; the satellite test site is Seattle Children's Hospital. All patients have isolated cleft lip and palate and a skeletal Class III malocclusion.Material and Methods: A total of 50 patients, ages 11-14, will be recruited for the maxillary protraction cohort. The maxillary surgery cohort consists of 50 patients, ages 16-21, who will undergo LeFort 1 maxillary advancement surgery. Patients with additional medical or cognitive handicaps were excluded from the study.Results: Current recruitment of patients is on track to complete the study within the proposed recruitment period.Conclusion: This observational trial is collecting information that will examine dental, skeletal, financial and quality-of-life issues from both research cohorts. [ABSTRACT FROM AUTHOR]

Objective: To determine the effects on weight loss of three abbreviated behavioral weight loss interventions with and without coaching and mobile technology.Methods: A randomized controlled efficacy study of three 6-month weight loss treatments was conducted in 96 adults with obesity: 1) self-guided (SELF), 2) standard (STND), or 3) technology-supported (TECH). STND and TECH received eight in-person group treatment sessions. SELF and STND used paper diaries to self-monitor diet, activity, and weight; TECH used a smartphone application with social networking features and wireless accelerometer.Results: Weight loss was greater for TECH and STND than SELF at 6 months (-5.7 kg [95% confidence interval: -7.2 to -4.1] vs. -2.7 kg [95% confidence interval: -5.1 to -0.3], P < 0.05) but not 12 months. TECH and STND did not differ except that more STND (59%) than TECH (34%) achieved ≥ 5% weight loss at 6 months (P < 0.05). Self-monitoring adherence was greater in TECH than STND (P < 0.001), greater in both interventions than SELF (P < 0.001), and covaried with weight loss (r(84) = 0.36-0.51, P < 0.001).Conclusions: Abbreviated behavioral counseling can produce clinically meaningful weight loss regardless of whether self-monitoring is performed on paper or smartphone, but long-term superiority over standard of care self-guided treatment is challenging to maintain. [ABSTRACT FROM AUTHOR]

Aim: To evaluate an innovative paediatric neurorehabilitation model in relation to improving quality of neurorehabilitation and reducing length of stay (LOS) for children with acquired brain injury.Method: A process evaluation approach was conducted in line with Medical Research Council evaluation of complex interventions guidance. Analysis was conducted on routinely collected patient data from 2017 to 2018, including LOS and family feedback. Descriptive and inferential statistics were used for quantitative analysis and qualitative data was analysed thematically.Results: Outcomes for 70 children (0-16y, median age 5y, IQR 1-11y, 46 males, 24 females) referred to the service indicated improved function and reduced complexity of need. The mean LOS was 10.6 days compared to baseline mean LOS of 41 days (2011-2012). High satisfaction from the families was recorded; however, ongoing needs and service gaps regarding long-term support were identified.Interpretation: This service model is effective in delivering quality paediatric neurorehabilitation, demonstrating a sustained impact on LOS, and positive patient outcome data and family feedback for this group of patients. What this paper adds Investment in early intensive neurorehabilitation and supported discharge impacts length of stay (LOS) for children with acquired brain injury. Early intensive neurorehabilitation and supported discharge is effective. This is demonstrated by a sustained reduction in LOS, positive patient outcomes, and family feedback. [ABSTRACT FROM AUTHOR]

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Surrogate endpoints play an important role in drug development when they can be used to measure treatment effect early compared to the final clinical outcome and to predict clinical benefit or harm. Such endpoints are assessed for their predictive value of clinical benefit by investigating the surrogate relationship between treatment effects on the surrogate and final outcomes using meta-analytic methods. When surrogate relationships vary across treatment classes, such validation may fail due to limited data within each treatment class. In this paper, two alternative Bayesian meta-analytic methods are introduced which allow for borrowing of information from other treatment classes when exploring the surrogacy in a particular class. The first approach extends a standard model for the evaluation of surrogate endpoints to a hierarchical meta-analysis model assuming full exchangeability of surrogate relationships across all the treatment classes, thus facilitating borrowing of information across the classes. The second method is able to relax this assumption by allowing for partial exchangeability of surrogate relationships across treatment classes to avoid excessive borrowing of information from distinctly different classes. We carried out a simulation study to assess the proposed methods in nine data scenarios and compared them with subgroup analysis using the standard model within each treatment class. We also applied the methods to an illustrative example in colorectal cancer which led to obtaining the parameters describing the surrogate relationships with higher precision. [ABSTRACT FROM AUTHOR]

Aim: To assess the responsiveness, concurrent validity, and feasibility of the Dyskinesia Impairment Scale (DIS) in non-ambulatory patients with dyskinetic cerebral palsy (CP).Method: The study is a secondary analysis of data collected in the IDYS trial, a randomized controlled trial on the effects of intrathecal baclofen (ITB). The DIS and Barry-Albright Dystonia Scale (BADS) were conducted at baseline and after 3 months of ITB or placebo treatment. Responsiveness was assessed by comparing the effect sizes and correlation of change after treatment between the DIS and BADS. Concurrent validity was evaluated by assessing the correlations between scales. Feasibility was evaluated for each DIS item by the number of participants who successfully accomplished the item.Results: Thirty-three non-ambulatory patients (9 females, 24 males) with dyskinetic CP (ITB-treated: n=17, mean [SD] age: 14y 1mo [4y 1mo]; placebo-treated: n=16, mean [SD] age: 14y 7mo [4y]) were included in the study. The effect sizes for BADS and DIS were similar in The ITB-treated group (-0.29 and -0.22 respectively). Changes after treatment on the DIS dystonia subscale correlated with changes on the BADS (r=0.64; p<0.001). The DIS dystonia subscale and BADS correlated at baseline and follow-up (r=0.78; p<0.001 and r=0.79; p<0.001). Not all DIS activity items could be performed in this sample of patients.Interpretation: For non-ambulatory patients with dyskinetic CP, the responsiveness of the DIS equalled the responsiveness of BADS. Concurrent validity was adequate. Feasibility for activity items was restricted in patients with severe dyskinetic CP.What This Paper Adds: The Dyskinesia Impairment Scale (DIS) and Barry-Albright Dystonia Scale showed similar responsiveness in non-ambulatory patients with dyskinetic cerebral palsy (CP). No floor or ceiling effect was observed for DIS in non-ambulatory participants. The concurrent validity of DIS was adequate in non-ambulatory participants. Patients with dyskinetic CP in Gross Motor Function Classification System levels IV and V could not perform all DIS activity items. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate tolerability of and response to rituximab in children with myelin oligodendrocyte glycoprotein (MOG) antibody-positive relapsing neuroinflammatory disease. This was an observational study of prospectively collected data on 12 consecutive children (eight females, four males; median age at onset 10y 6mo [interquartile range {IQR} 7y 2mo-12y 5mo], median follow-up 2y 1mo [IQR 1y 7mo-2y 6mo]) with central nervous system inflammation and persistent serum MOG immunoglobulin G positivity more than 12 weeks after clinical presentation. Patients received a standardized rituximab treatment protocol. MOG antibody testing was performed following standardized cell-based methods. Median clinical follow-up after rituximab induction was 2 years (IQR 1y 7mo-2y 10mo). The relapse rate in the first 12 months posttreatment was 0 (IQR 0-0). After rituximab, two patients relapsed during B-cell suppression and four showed clinical or radiological disease recurrences at B-cell reconstitution. Mild-to-moderate infusion related adverse events occurred in two patients. Leukopenia developed in seven patients and serum immunoglobulin suppression in five patients with no significant age effect on the risk of their development. None developed severe life-threatening events. Rituximab-induced B-cell suppression was associated with absence of relapses in 10 patients who were MOG-positive with recurrent disease. Rituximab was well tolerated. The most frequent adverse effects were hypogammaglobulinemia and leukopenia. We recommend monitoring of complete blood counts and immunoglobulins in this population. WHAT THIS PAPER ADDS: Rituximab appears to control disease in most anti-myelin oligodendrocyte glycoprotein-positive patients with relapsing neuroinflammatory disease. Rituximab was associated with transitory, mild-to-moderate infusion-related effects. Half of patients treated with rituximab developed leukopenia or hypogammaglobulinemia. No opportunistic infections were observed. [ABSTRACT FROM AUTHOR]

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: The use of relative and absolute effect estimates has important implications for the interpretation of study findings. Likewise, examining additive and multiplicative interaction can lead to differing conclusions about the joint effects of two exposure variables. The aim of this paper is to examine the relationship between BMI and mortality on the relative and absolute scales and investigate interaction between BMI and age.Methods: Data from 68,132 participants in the Women's Health Initiative (WHI) study were used. The risk ratio and risk difference of BMI on mortality were estimated. A product term was also included to examine interaction between BMI and age on the multiplicative scale, and the relative excess risk of interaction was calculated to measure additive interaction.Results: Results demonstrated that the mortality risk ratio decreased as women aged, but the mortality risk difference increased as women aged. Evidence of additive and multiplicative interaction between age and BMI was found.Conclusions: In postmenopausal women, the relative mortality risk associated with high BMI decreased with increasing age, but the absolute risk of high BMI increased with increasing age. This indicates the importance of considering the interaction between age and BMI to understand mortality risk in older women. [ABSTRACT FROM AUTHOR]

The relative risk, risk difference, and odds ratio are three major indices of differences in risks of diseases between different groups. Although widely used in research and practice in biomedical and epidemiologic research, misconceptions are not uncommon about their relationships. Many publications offer contradicting advices in how to use them in studies. Some biomedical researchers believe that these indices are related in a monotone fashion, and, thus, changes in one direction in one of the indices can be interpreted as same directional changes in the other two. Misconceptions about these three indices such as the monotone relationship are so prevalent in the biomedical and epidemiologic research that clarifications of such popular beliefs are warranted. In this paper, we take a systematic approach to characterize the relationships among the indices. We develop key results to elucidate the intricate relationships between the indices. Our findings speak to the need for investigators to carefully consider the different indices before using them in their studies, since they are not interchangeable and results based on one index are generally not translatable into any of the others. [ABSTRACT FROM AUTHOR]

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The incidence of a peri-implant soft tissue dehiscence/deficiency (PSTD) is not a rare finding. Despite multiple previous attempts aimed at correcting the PSTDs, a classification of these conditions has not yet been proposed. This lack in the literature may also lead to discrepancies in the reported treatment outcomes and thus misinform the clinician or the readers. The aim of the present article was therefore to present a classification of peri-implant PSTD at a single implant site.Methods: Four classes of PSTDs were discussed based on the position of the gingival margin of the implant-supported crown in relation to the homologous natural tooth. In addition, the bucco-lingual position of the implant head was also taken into consideration. Each class was further subdivided based on the height of the anatomical papillae.Results: Subsequently, for each respective category a surgical approach (including bilaminar techniques, the combined prosthetic-surgical approach or soft tissue augmentation with a submerged healing) was also suggested.Conclusion: This paper provides a new classification system for describing PSTDs at single implant sites, with the appropriate recommended treatment protocol. [ABSTRACT FROM AUTHOR]

In this paper, we present a unified modeling framework to combine aggregated data from randomized controlled trials (RCTs) with individual participant data (IPD) from observational studies. Rather than simply pooling the available evidence into an overall treatment effect, adjusted for potential confounding, the intention of this work is to explore treatment effects in specific patient populations reflected by the IPD. In this way, by collecting IPD, we can potentially gain new insights from RCTs' results, which cannot be seen using only a meta-analysis of RCTs. We present a new Bayesian hierarchical meta-regression model, which combines submodels, representing different types of data into a coherent analysis. Predictors of baseline risk are estimated from the individual data. Simultaneously, a bivariate random effects distribution of baseline risk and treatment effects is estimated from the combined individual and aggregate data. Therefore, given a subgroup of interest, the estimated treatment effect can be calculated through its correlation with baseline risk. We highlight different types of model parameters: those that are the focus of inference (e.g., treatment effect in a subgroup of patients) and those that are used to adjust for biases introduced by data collection processes (e.g., internal or external validity). The model is applied to a case study where RCTs' results, investigating efficacy in the treatment of diabetic foot problems, are extrapolated to groups of patients treated in medical routine and who were enrolled in a prospective cohort study. [ABSTRACT FROM AUTHOR]

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Mediation analysis allows the examination of effects of a third variable in the pathway between an exposure and an outcome. The general multiple mediation analysis method, proposed by Yu et al, improves traditional methods (eg, estimation of natural and controlled direct effects) to enable consideration of multiple mediators/confounders simultaneously and the use of linear and nonlinear predictive models for estimating mediation/confounding effects. In this paper, we extend the method for time-to-event outcomes and apply the method to explore the racial disparity in breast cancer survivals. Breast cancer is the most common cancer and the second leading cause of cancer death among women of all races. Despite improvement of survival rates of breast cancer in the US, a significant difference between white and black women remains. Previous studies have found that more advanced and aggressive tumors and less than optimal treatment may explain the lower survival rates for black women as compared to white women. Due to limitations of current analytic methods and the lack of comprehensive data sets, researchers have not been able to differentiate the relative effect each factor contributes to the overall racial disparity. We use the CDC-funded Patterns of Care study to examine the determinants of racial disparities in breast cancer survival using a novel multiple mediation analysis. Using the proposed method, we applied the Cox hazard model and multiple additive regression trees as predictive models and found that all racial disparity in survival among Louisiana breast cancer patients were explained by factors included in the study. [ABSTRACT FROM AUTHOR]

In this paper, we propose a large-scale multiple testing procedure to find the significant sub-areas between two samples of curves automatically. The procedure is optimal in that it controls the directional false discovery rate at any specified level on a continuum asymptotically. By introducing a nonparametric Gaussian process regression model for the two-sided multiple test, the procedure is computationally inexpensive. It can cope with problems with multidimensional covariates and accommodate different sampling designs across the samples. We further propose the significant curve/surface, giving an insight on dynamic significant differences between two curves. Simulation studies demonstrate that the proposed procedure enjoys superior performance with strong power and good directional error control. The procedure is also illustrated with the application to two executive function studies in hemiplegia. [ABSTRACT FROM AUTHOR]

Clinical trials are often designed to compare treatments on the basis of multiple outcomes. For the analysis of the treatment comparison from such a trial, in 1999, the Finkelstein-Schoenfeld test was proposed, which was a generalization of the Gehan-Wilcoxon test based on pairwise comparison of patients on a primary outcome when possible but otherwise on a secondary outcome. In 2012, Pocock and colleagues suggested an estimate based on this concept, the Win Ratio, which summarized the ratio of the number of patients who fared better versus worse on the experimental arm. However, in 2016, Oakes noted that the Win Ratio could be a function of the distribution of follow-up times of the trial. The aim of this paper is to propose an approach to representing the Win Ratio graphically in such a way that the effect of time on the estimate would be apparent. In addition, the methods are used to display the contribution of each endpoint to the composite. We apply the methods to clinical trials in cancer, cardiology, and neurology. Software is available named winRatioAnalysis in CRAN. [ABSTRACT FROM AUTHOR]

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aims: To review systematically the use of intravenous (IV) inotropic agents acting through the adrenergic signalling pathway, compared with placebo or an active agent, in patients with heart failure.Methods: Studies investigating the use of intravenous inotropes in patients with heart failure published between 1966 and 2000 were identified using MEDLINE, the Cochrane register and Embase databases. Reference lists from relevant papers and reviews were hand searched for further papers. In total, 21 trials, that included 632 patients receiving IV inotropic drugs, placebo or non-treatment control, were identified. Drugs of the following classes were included, the beta-agonists; dobutamine, high-dose (>2.5 microg/kg/min) dopamine, dopexamine and the phosphodiesterase (PDE) inhibitors; amrinone, milrinone, enoximone and toborinone. Sixteen trials (474 patients) contributed data from acute invasive haemodynamic studies of symptomatically severe heart failure. Five trials (158 patients) were based on intermittent inotropic therapy in an outpatient context.Results: With few exceptions, trials of intravenous inotropic agents were small and often failed to report clinically important outcomes. Compared to placebo, intravenous inotropic agents acting through the adrenergic system tended to increase mortality (odds ratio 1.50 (95% CI=0.51 to 3.92) but this did not reach significance and insufficient data were available to determine whether symptoms improved. There appeared to be little difference in the effect of beta-agonists compared to PDE inhibitors on patient outcomes but this could be attributed to the paucity of data.Conclusions: Intravenous inotropic agents acting through the adrenergic pathway are often used in patients with worsening heart failure to achieve arbitrary haemodynamic targets. Our analyses show that there is very little evidence that such treatment improves symptoms or patient outcomes and may not be safe. This highlights the need for further well designed randomised clinical trials. [ABSTRACT FROM AUTHOR]

Current guidelines focus on conventional dialysis defined as 3-5 hours, three times per week, and suggest that longer or more frequent dialysis be considered. This paper presents the case for considering that shorter or less frequent dialysis should also be considered. More frequent and/or longer dialysis facilitates control of fluid overload, blood pressure, and phosphate levels. These benefits will require time to translate into probable hard outcome improvement. Patients are unlikely to participate in productive or pleasurable activities while undergoing dialysis in center or traveling to treatment. So any increase in dialysis time or frequency, during awake hours, will result in an immediate and quantifiable reduction in quality of life. Conventional measures of dialysis adequacy consider only urea clearance. This poorly reflects middle molecule clearance, renal function, and management of fluid and phosphate overload, all of which have a greater impact on outcome than urea clearance. Fluid, phosphate, and uremic toxin overload may be better and less invasively controlled by continuous means such as dietary modification, binders, and preserving renal function. Bioimpedance, blood volume monitoring, and lung ultrasound provide means for improved control of fluid homeostasis. The probability of renal function recovery or preservation is increased by avoiding dehydration. An ideal strategy would be to preserve renal function and employ as little dialysis as possible (if it cannot be avoided altogether). Fluid overload, blood pressure, uremic toxin, and phosphate levels would be monitored and controlled using any means available, preferably by less invasive means than dialysis. Kt/V is useful in controlling the prescribed dose of dialysis, but the achievement of a universal target should not be an end in itself. [ABSTRACT FROM AUTHOR]

This paper considers the analysis of a repeat event outcome in clinical trials of chronic diseases in the context of dependent censoring (e.g. mortality). It has particular application in the context of recurrent heart failure hospitalisations in trials of heart failure. Semi-parametric joint frailty models (JFMs) simultaneously analyse recurrent heart failure hospitalisations and time to cardiovascular death, estimating distinct hazard ratios whilst individual-specific latent variables induce associations between the two processes. A simulation study was carried out to assess the suitability of the JFM versus marginal analyses of recurrent events and cardiovascular death using standard methods. Hazard ratios were consistently overestimated when marginal models were used, whilst the JFM produced good, well-estimated results. An application to the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity programme was considered. The JFM gave unbiased estimates of treatment effects in the presence of dependent censoring. We advocate the use of the JFM for future trials that consider recurrent events as the primary outcome. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

In clinical trials with survival endpoint, it is common to observe an overlap between two Kaplan-Meier curves of treatment and control groups during the early stage of the trials, indicating a potential delayed treatment effect. Formulas have been derived for the asymptotic power of the log-rank test in the presence of delayed treatment effect and its accompanying sample size calculation. In this paper, we first reformulate the alternative hypothesis with the delayed treatment effect in a rescaled time domain, which can yield a simplified sample size formula for the log-rank test in this context. We further propose an intersection-union test to examine the efficacy of treatment with delayed effect and show it to be more powerful than the log-rank test. Simulation studies are conducted to demonstrate the proposed methods. [ABSTRACT FROM AUTHOR]

The present paper reports on a 5-year follow-up of a randomized reading intervention in grade 3 in Sweden. An intervention group (n = 57) received daily training for 12 weeks in phoneme/grapheme mapping, reading comprehension and reading speed, whereas a control group (n = 55) participated in ordinary classroom activities. The main aim was to investigate if there were remaining effects of the intervention on reading-related skills. Previous analyses showed that the intervention group performed significantly better than the control group on spelling, reading speed, reading comprehension and phoneme awareness at the immediate post-test with sustained effects 1 year later. Results from the 5-year follow-up show that the only significant difference between the intervention (n = 47) and the control group (n = 37) was on word decoding. There was also a significant interaction effect of group assignment and initial word decoding, in the way that the lowest-performing students benefitted the most from the intervention. Another aim was to examine if the children identified in a screening (n = 2212) as poor readers in grade 2 still performed worse than typical readers. The analyses showed that the typically developing students (n = 66) outperformed the students identified as poor readers in grade 2 on working memory, spelling, reading comprehension and word decoding. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objectives: Several studies have shown that perseverative, worrisome thoughts are prospectively related to subjective health complaints (SHC) and that a short worry postponement intervention can decrease these complaints. As SHC and worry are prevalent and costly, we tested whether the intervention can be offered online to reduce these complaints in the general population.Design: A randomized parallel-group trial was conducted with self-selected participants from the general population.Methods: Via the research website, 996 participants were instructed to register their worrying for 6 consecutive days. The intervention group was instructed to postpone worry to a special 30-min period in the early evening. The Subjective Health Complaints inventory, as administered before and after the intervention, and daily worry frequency and duration were considered the primary outcomes.Results: Three hundred and sixty-one participants completed the study. Contrary to our expectation, the registration group (n = 188) did not differ from the intervention group (n = 163) in SHC (ηp² = .000, CI [0.000-0.003]), or in worry frequency or duration. Nevertheless, the different worry parameters were moderately related to SHC (r between .238 and .340, p ≤ .001).Conclusions: In contrast to previous studies using pen-and-pencil versions of the worry postponement intervention, this study suggests that a direct online implementation was not effective in reducing SHC and worry. Overall, participants had high trait worry levels and reported difficulty with postponing worrying. Reducing SHC and worries via the Internet might require more elaborate interventions that better incorporate the advantages of delivering interventions online.Statement Of Contribution: What is already known on this subject? The perseverative cognition hypothesis argues that perseverative cognition, such as worry and rumination, acts as a mediator by which psychosocial stress may produce negative health effects. Prior research has indeed shown that worry and subjective health complaints (SHC) are prospectively related, but causality studies - that is, showing that changes in worry induce changes in health outcomes - are scarce and have mainly been conducted in young samples. These studies showed that reducing worry, using a worry postponement intervention, can reduce daily worrying and SHC. What does this study add? Trait and daily worrying are associated with SHC. An online worry postponement intervention is ineffective in reducing worry and SHC. Paper-and-pencil interventions cannot directly be used as online interventions. [ABSTRACT FROM AUTHOR]

Interventions with multivalued treatments are common in medical and health research, such as when comparing the efficacy of competing drugs or interventions, or comparing between various doses of a particular drug. In recent years, there has been a growing interest in the development of multivalued treatment effect estimators using observational data. In this paper, we compare the performance of commonly used regression-based methods that estimate multivalued treatment effects based on the unconfoundedness assumption. These estimation methods fall into three general categories: (i) estimators based on a model for the outcome variable using conventional regression adjustment; (ii) weighted estimators based on a model for the treatment assignment; and (iii) 'doubly-robust' estimators that model both the treatment assignment and outcome variable within the same framework. We assess the performance of these models using Monte Carlo simulation and demonstrate their application with empirical data. Our results show that (i) when models estimating both the treatment and outcome are correctly specified, all adjustment methods provide similar unbiased estimates; (ii) when the outcome model is misspecified, regression adjustment performs poorly, while all the weighting methods provide unbiased estimates; (iii) when the treatment model is misspecified, methods based solely on modeling the treatment perform poorly, while regression adjustment and the doubly robust models provide unbiased estimates; and (iv) when both the treatment and outcome models are misspecified, all methods perform poorly. Given that researchers will rarely know which of the two models is misspecified, our results support the use of doubly robust estimation. [ABSTRACT FROM AUTHOR]

Background: The great majority of post-infarction studies of beta-blockers were conducted in an era when these agents were widely held to be contra-indicated for the management of heart failure. We now know that beta-blockers are highly effective for the management of patients with chronic stable heart failure. However, there remains uncertainty about their role in the setting of post-infarction heart failure and ventricular dysfunction.Aim: the primary objective in this paper, was to investigate the extent to which heart failure or evidence of major cardiac dysfunction influenced outcome in previous trials of beta-blockers in heart failure after myocardial infarction.Methods: We assessed the extent to which the inclusion of patients with heart failure or major cardiac dysfunction influenced outcome in randomised trials of long-term use of beta-blockade after myocardial infarction. The primary analysis was to assess the extent to which the proportion of patients included in each trial with heart failure influenced the relative odds of all-cause mortality in the trials. All randomised trials without crossover with treatment lasting more than one month and with 50 or more patients were considered. All those that provided information on the proportion of patients with heart failure or major cardiac dysfunction in the original or subsequent articles were included in the analysis.Results: Overall treatment with a beta-blocker was associated with a 22.6% reduction in the odds of death (95% C1 11-32.3%). There were very few data on the effects of beta-blockers after myocardial infarction in patients with documented left ventricular systolic dysfunction. In the analysis that included heart failure as a factor, treatment with a beta-blocker was associated with a non-significant interaction with the presence of heart failure. However, because the group including heart failure patients were at higher risk, the absolute benefit of treatment with beta-blockers appeared greater in this group.Conclusions: This analysis suggests that the relative benefit of beta-blockers on mortality after a myocardial infarction is similar in the presence or absence of heart failure but that the absolute benefit may be greater in the former. However, as current clinical practice has changed radically from the time when the majority of these trials were conducted, further trial evidence would be desirable. [ABSTRACT FROM AUTHOR]

Background: Motivated by the setting of clinical trials in low back pain, this work investigated statistical methods to identify patient subgroups for which there is a large treatment effect (treatment by subgroup interaction). Statistical tests for interaction are often underpowered. Individual patient data (IPD) meta-analyses provide a framework with improved statistical power to investigate subgroups. However, conventional approaches to subgroup analyses applied in both a single trial setting and an IPD setting have a number of issues, one of them being that factors used to define subgroups are investigated one at a time. As individuals have multiple characteristics that may be related to response to treatment, alternative exploratory statistical methods are required.Methods: Tree-based methods are a promising alternative that systematically searches the covariate space to identify subgroups defined by multiple characteristics. A tree method in particular, SIDES, is described and extended for application in an IPD meta-analyses setting by incorporating fixed-effects and random-effects models to account for between-trial variation. The performance of the proposed extension was assessed using simulation studies. The proposed method was then applied to an IPD low back pain dataset.Results: The simulation studies found that the extended IPD-SIDES method performed well in detecting subgroups especially in the presence of large between-trial variation. The IPD-SIDES method identified subgroups with enhanced treatment effect when applied to the low back pain data.Conclusions: This work proposes an exploratory statistical approach for subgroup analyses applicable in any research discipline where subgroup analyses in an IPD meta-analysis setting are of interest. [ABSTRACT FROM AUTHOR]

Introduction and Aims: The Australian Treatment Outcomes Profile (ATOP) is a brief instrument that assesses a range of substance use, health and well-being measures over the past 28 days. Previously, it has been validated in general adult Australian alcohol and other drug (AOD) treatment populations. However, the increasing number of older-aged clients attending AOD treatment warrants the instrument to be validated for this population. The aim of this study was to validate the ATOP for use in older AOD populations, by comparing it with validated 'gold standard' measures used in older populations.Design and Methods: A convenience sample of 99 participants aged ≥50 attending specialist AOD services in Sydney, Australia were administered the ATOP by a researcher, along with alcohol use (AUDIT) and health questionnaires [Physical Health Questionnaire-15, 12-item short-form Health Survey (SF-12) and Geriatric Depression Scale].Results: The ATOP items had strong agreement with the comparison instruments. The highest correlation was between the 28 days alcohol use and the AUDIT. ATOP psychological health scores highly correlated with the SF-12 mental health subscale and the Geriatric Depression Scale, and ATOP physical health scores significantly correlated with the SF-12 physical health subscale and the Physical Health Questionnaire-15. The ATOP Quality of Life score significantly correlated with all health measures. Discussion and Conclusions The ATOP has good concurrent validity with other validated substance use and health measures in an older population. Comparison with general older populations demonstrated the poorer health of this group of older AOD clients in particular.[Lintzeris N, Monds L A, Rivas G, Leung S, Withall A, Draper B. The Australian Treatment Outcomes Profile instrument as a clinical tool for older alcohol and other drug clients: A validation study. Drug Alcohol Rev 2016;35:673-677]. [ABSTRACT FROM AUTHOR]

Background and Aims: Baclofen, a selective γ-aminobutyric acid (GABA)B receptor agonist, has emerged as a potential treatment for alcohol use disorder with much unexplained variation in response to treatment efficacy and dose regimen. Several positive studies include patients with alcoholic liver disease (ALD) and/or history of heavy drinking. The aim of this paper was to examine the association of cortical GABA+ concentration with severity of liver disease (including markers of liver injury) and other clinical characteristics in alcohol patients.Methods: Proton magnetic resonance spectroscopy (1 H-MRS), from the parietal lobe, was analyzed to yield absolute concentration of GABA in 24 alcohol-dependent individuals. Diagnosis of ALD, markers of liver injury, severity of liver disease (Model for End-Stage Liver Disease [MELD]), and alcohol history were assessed. Covariates included concurrent medication, age, and recent alcohol consumption.Results: Multiple linear regression revealed that GABA+ concentration was significantly predicted by MELD scores (F = 5.02, R2  = 0.59, P = 0.01; MELD: B = -0.63, P = 0.02), when controlling for covariates concurrent medication, age, and recent alcohol consumption.Conclusion: Severity of ALD is associated with lower cortical concentrations of GABA+. These results may explain variations in response to the GABAB agonist, baclofen, in the alcohol-dependent population. [ABSTRACT FROM AUTHOR]

Background: Tissue regeneration within the periodontally involved furcation area is one of the most challenging aspects of periodontal surgery. The aim of this study was to evaluate the additional benefit of leukocyte and platelet-rich fibrin (L-PRF) to autogenous bone grafts (ABGs) in the treatment of mandibular molar degree II furcation involvement, comparing the clinical outcomes with those from open flap debridement (OFD)+ABG and OFD alone treatments.Methods: Fifty-four patients, exhibiting one buccal or lingual mandibular molar furcation defect, were randomly assigned to three treatment groups: OFD+ABG+L-PRF (n = 18); OFD+ABG (n = 18); and OFD (n = 18). Clinical (probing depth [PD], horizontal clinical attachment level [HCAL], vertical clinical attachment level [VCAL], gingival recession [GR]) and radiographic (vertical bone level [VBL]) parameters were evaluated at baseline and 6 months after treatment. HCAL change was the primary outcome.Results: No significant differences within each group were reported for GR changes, but statistically significant improvements in HCAL, VCAL, PD, and VBL were observed in all groups, except for VBL in the OFD group. At 6 months, the mean HCAL gain was 2.29 ± 0.18 mm in the OFD+ABG+L-PRF group, which was significantly greater than that in the OFD+ABG (1.61 ± 0.18 mm) and OFD (0.86 ± 0.18 mm) groups. Both OFD+ABG+L-PRF and OFD+ABG therapies produced a significantly greater clinical and radiographic improvement than OFD.Conclusion: The addition of L-PRF to ABG produces a significantly greater HCAL gain and PD reduction as compared with OFD+ABG treatment in mandibular degree II furcation involvements. [ABSTRACT FROM AUTHOR]

A dynamic treatment regime (DTR) is a sequence of decision rules, each of which recommends a treatment based on a patient's past and current health status. Sequential, multiple assignment, randomized trials (SMARTs) are multi-stage trial designs that yield data specifically for building effective DTRs. Modeling the marginal mean trajectories of a repeated-measures outcome arising from a SMART presents challenges, because traditional longitudinal models used for randomized clinical trials do not take into account the unique design features of SMART. We discuss modeling considerations for various forms of SMART designs, emphasizing the importance of considering the timing of repeated measures in relation to the treatment stages in a SMART. For illustration, we use data from three SMART case studies with increasing level of complexity, in autism, child attention deficit hyperactivity disorder, and adult alcoholism. In all three SMARTs, we illustrate how to accommodate the design features along with the timing of the repeated measures when comparing DTRs based on mean trajectories of the repeated-measures outcome. [ABSTRACT FROM AUTHOR]

Background and Objectives: We examined youth recovery outcomes at 6- and 9-months post-participation in an aftercare pilot study called Educating and Supporting inQuisitive Youth in Recovery (ESQYIR) that aimed to investigate the utility of a 12-week mobile texting recovery support intervention.Methods: A total of 80 youth [Mage 20.4 (SD = 3.5)] were randomized to a mobile texting aftercare intervention or an aftercare-as-usual control group. Both groups received identical data collection protocols with psychosocial and behavioral assessments occurring at baseline, during the trial (months 1 and 2), at discharge from the trial (month 3), and 3-, 6-, and 9-month post-intervention follow-ups.Results: Mixed modeling showed that youth who participated in the mobile texting aftercare intervention were less likely to test positive for their primary drug compared to youth in the aftercare-as-usual condition during 6- and 9-months follow-ups (p < .01). Additionally, youth in the aftercare intervention reported significantly higher self-efficacy/confidence to abstain during recovery (p < .05) and were more likely to participate in recovery-related behaviors (self-help and goal-directed extracurricular activities; p < .05) than those in aftercare-as-usual at the 6- and 9-month follow-ups.Conclusions: Results suggest that delivering a structured, behavioral-based wellness aftercare intervention using mobile texting can be an effective for sustaining recovery outcomes in youth over time compared to youth who receive aftercare-as-usual.Scientific Significance: This study shows that a mobile-texting aftercare intervention sustained effects at 6- and 9-months post-intervention for young people in substance use recovery. [ABSTRACT FROM AUTHOR]

Background: Current guidelines recommend that antihyperglycaemic treatment in patients with type 2 diabetes not achieving the HbA1c target on basal insulin should be intensified with a glucagon-like peptide-1 receptor agonist (GLP-1RA) or basal-plus/basal-bolus (BP/BB) insulin regimen. We conducted a systematic review and meta-analysis to compare the effects of GLP-1RA/insulin combinations versus BP/BB.Methods: The review was registered on PROSPERO (CRD42017079547). PubMed, Scopus, CENTRAL, and ClinicalTrials.gov were searched until July 2018. All randomized controlled trials (RCTs) reporting HbA1c , body weight, daily insulin dose, hypoglycaemic events, and discontinuation due to lack of efficacy were included. A subgroup analysis on different combinations of GLP-1RA and insulin was performed.Results: Out of 1885 retrieved papers, 13 RCTs were included in the review. Compared with BP/BB, GLP-1RA/insulin combinations were associated with a similar HbA1c reduction (Δ = -0.06%; 95% confidence interval [CI], -0.14 to 0.02; P = 0.13; I2  = 52%), greater weight loss (Δ = -3.72 kg; 95% CI, -4.49 to -2.95; P < 0.001; I2  = 89%), and lower incidence of hypoglycaemic events (relative risk [RR] = 0.46; 95% CI, 0.38-0.55; P < 0.001; I2  = 99%). The daily insulin dosage among GLP-1RA/insulin users was 30.3 IU/day (95% CI, -41.2 to -19.3; P < 0.001; I2  = 94%), lower than with BP/BB. No difference was found for discontinuation due to lack of efficacy.Conclusions: The present review supports treatment intensification with GLP-1RA added to insulin versus BP/BB in uncontrolled type 2 diabetes. This could provide similar antihyperglycaemic efficacy while leading to weight loss and sparing of hypoglycaemia and insulin dose. As a consequence, a considerable number of patients with type 2 diabetes could be potentially shifted from BP/BB to GLP-1RA/insulin combinations. [ABSTRACT FROM AUTHOR]

Objective: A first-in-human responsive deep brain stimulation (rDBS) trial (NCT03868670) for obesity is under way, which is based on promising preclinical evidence. Given the upfront costs of rDBS, it is prudent to examine the success threshold for cost-effectiveness compared with laparoscopic Roux-en-Y gastric bypass (LRYGB).Methods: Efficacy and safety data on LRYGB and safety data on rDBS were collected for established indications through a literature search. The success threshold was defined as minimum BMI reduction. Treatment costs were calculated via Medicare national reimbursement data.Results: LRYGB had a mean BMI reduction of 13.75 kg/m2 . Based on adverse events, LRYGB was a less-preferred health state (overall adverse event utility of 0.96 [0.02]) than rDBS (0.98 [0.01]), but LRYGB ($14,366 [$6,410]) had a significantly lower treatment cost than rDBS ($29,951 [$4,490]; p < 0.0001). Therefore, for rDBS to be cost-effective compared with LRYGB, the multiple models yielded a success threshold range of 13.7 to 15.2 kg/m2 .Conclusions: This study established a preliminary efficacy success threshold for rDBS to be cost-effective for severe obesity, and results from randomized controlled trials are needed. This analysis allows for interpretation of the economic impact of advancing rDBS for obesity in light of ongoing trial results and suggests an attainable threshold is needed for cost-effectiveness. [ABSTRACT FROM AUTHOR]

Background and Purpose: The risk for cardiovascular events including venous and arterial disease and stroke is elevated after treatment with estrogen and medroxyprogesterone acetate (MPA) in postmenopausal women. Here, we have investigated the effect of MPA on arterial thrombosis and atherosclerosis in a murine model of atherosclerosis.Experimental Approach: Apolipoprotein E (ApoE)-/- mice were bilaterally ovariectomized and treated with placebo, MPA (27.7 microg day(-1)) and MPA + 17-beta-oestradiol (E2; 1.1 microg day(-1)) for 90 days, on a Western-type diet. Thrombotic response was measured in a photothrombosis model, platelet activation by fluorescence activated cell sorting (FACS) analysis (CD62P) and thrombin generation by the endogenous thrombin potential (ETP). Furthermore, aortic plaque burden and aortic root plaque composition were determined.Key Results: MPA and MPA + E2-treated animals showed an aggravated thrombotic response shown by significantly reduced time to stable occlusion. The pro-thrombotic effect of MPA was paralleled by increased ETP whereas platelet activation was not affected. Furthermore, MPA + E2 reduced the number of cells positive for alpha-smooth muscle actin and increased hyaluronan in the plaque matrix. Interestingly, total plaque burden was reduced by MPA but unchanged by MPA + E2.Conclusion and Implications: Long-term treatment with MPA and MPA + E2 increased arterial thrombosis despite inhibitory effects of MPA on atherosclerosis in ApoE-deficient mice. Increased thrombin formation, reduced smooth muscle content and remodelling of non-collagenous plaque matrix may be involved in the pro-thrombotic effects. Thus, MPA exhibits differential effects on arterial thrombosis and on atherosclerosis. [ABSTRACT FROM AUTHOR]

Background and Purpose: The aim of this study was to investigate the effect of chronic treatment with antihypertensive and non-antihypertensive doses of zofenopril on cardiovascular changes in spontaneously hypertensive rats (SHR).Experimental Approach: Male SHR were treated with 0.5 or 10 mg kg(-1) per day of zofenopril (Z(0.5) and Z(10)) for 3 months. SHR and Wistar-Kyoto rats (WKY) receiving vehicle were used as controls. Systolic blood pressure was measured using the tail cuff method. Left ventricular weight/body weight ratio was calculated as cardiac hypertrophy index. Angiotensin converting enzyme (ACE) activity was determined in plasma and tissues by a fluorimetric method. Vascular reactivity was evaluated on aortic rings by acetylcholine and sodium nitroprusside relaxations. Effects on vascular structure were assessed by lumen diameter, wall thickness and medial cross-sectional area determination. Superoxide anion generation was quantified using lucigenin-amplified chemiluminescence in aorta.Results: Long-term daily administration of zofenopril (10 mg kg(-1)) to SHR reduced blood pressure to WKY values, decreased cardiac hypertrophy, improved the acetylcholine-induced relaxant response and reversed the vascular remodelling. ACE inhibition and antioxidant activity were involved in these effects. 0.5 mg kg(-1) per day of zofenopril slightly modified blood pressure and the other effects were weaker.Conclusions and Implications: Antihypertensive effects of chronic treatment with zofenopril were accompanied by recovery of endothelial function and improvement of cardiovascular structure. Low-dose zofenopril had little effect on blood pressure, with some benefits on cardiovascular structure and function. Inhibition of ACE and antioxidant activity were involved in these effects. [ABSTRACT FROM AUTHOR]

Background and Purpose: ABC multidrug transporters (MDR-ABC proteins) cause multiple drug resistance in cancer and may be involved in the decreased anti-cancer efficiency and modified pharmacological properties of novel specifically targeted agents. It has been documented that ABCB1 and ABCG2 interact with several first-generation, small-molecule, tyrosine kinase inhibitors (TKIs), including the Bcr-Abl fusion kinase inhibitor imatinib, used for the treatment of chronic myeloid leukaemia. Here, we have investigated the specific interaction of these transporters with nilotinib, dasatinib and bosutinib, three clinically used, second-generation inhibitors of the Bcr-Abl tyrosine kinase activity.Experimental Approach: MDR-ABC transporter function was screened in both membrane- and cell-based (K562 cells) systems. Cytotoxicity measurements in Bcr-Abl-positive model cells were coupled with direct determination of intracellular TKI concentrations by high-pressure liquid chromatography-mass spectrometry and analysis of the pattern of Bcr-Abl phosphorylation. Transporter function in membranes was assessed by ATPase activity.Key Results: Nilotinib and dasatinib were high-affinity substrates of ABCG2, and this protein mediated an effective resistance in cancer cells against these compounds. Nilotinib and dasatinib also interacted with ABCB1, but this transporter provided resistance only against dasatinib. Neither ABCB1 nor ABCG2 induced resistance to bosutinib. At relatively higher concentrations, however, each TKI inhibited both transporters.Conclusions and Implications: A combination of in vitro assays may provide valuable preclinical information for the applicability of novel targeted anti-cancer TKIs, even in multidrug-resistant cancer. The pattern of MDR-ABC transporter-TKI interactions may also help to understand the general pharmacokinetics and toxicities of new TKIs. [ABSTRACT FROM AUTHOR]

Background: The purpose of this follow up study was to determine if a xenogeneic collagen matrix (CMX) is as effective as free gingival graft (FGG) in preventing further recession 6+ years following vestibuloplasty.Methods: This study was a single-blind (examiner), randomized, controlled, split-mouth study of 30 subjects with insufficient zones of KT (< 2 mm), associated with at least two, paired teeth. The study utilized a within subject treatment comparison to examine non-inferiority according to primary and secondary endpoints 6+ years after therapy. The original study primary efficacy endpoint was keratinized tissue width (KTw); however, in this report, prevention of recession (Rec) was also examined, along with traditional, secondary clinical measures, histopathology of mucosal biopsies and exploratory, patient reported outcomes (PROs) for pain and satisfaction.Results: A total of 23 of the 30 original, study patients were available for 6 to 8-year postoperative assessment, and these patients were representative of the original patient population. For preventing further Rec, CMX was not inferior to FGG (ΔRec = -0.07 ± 1.26 mm for CMX and -0.17 ± 0.78 mm for FGG, P = 0.710). There were no adverse results observed, and histological assessment indicated normal, keratinized gingiva for both therapies. Tissue texture and color match to surrounding, native tissues were significantly better for CMX, and patients preferred CMX over FGG therapy.Conclusions: CMX appears to be a suitable substitute for FGG 6+ years after therapy. [ABSTRACT FROM AUTHOR]

Aim: The aim of this paper is to investigate prospectively the potential benefits of the participation of the medical clowns in the outpatient paediatric penile surgery programme.Methods: Eighty children undergoing meatotomy, age 2 to 16 years, were randomised into two groups (40 each). In the first group, the medical clown was an integral part of the medical team, and in the second group, the treatment was given without participation of the medical clown. The following parameters were measured: the level of pre-operative anxiety, the level of the post-operative pain, the amount of pain medication use in the first 24 h after surgery and the time needed to return to normal activities. The operating room time and hospital costs were calculated.Results: The patients from the first group demonstrated a lower pre-operative anxiety index upon (P = 0.0319) and after surgery (P = 0.0042), required less induction time for anaesthesia (P < 0.001), spent overall less time in the operating room (P < 0.0001) and required less time to recover from the surgery and to be discharged (P = 0.0172). The overall OR time and post-operative unit care savings of 20 and 155 min, respectively, led to the cost savings of $467.Conclusion: Our data demonstrated that the use of the medical clown functioning as an integral part of the operating team reduces children pre-operative anxiety and leads to a shortening of the overall time in the hospital thereby reducing the overall medical cost justifying the participation of medical clown as an integral part of the health team in a paediatric urology outpatient surgical unit. [ABSTRACT FROM AUTHOR]