LOD score exclusion analyses for candidate QTLs using random population samples.

PubMed

Deng, Hong-Wen

2003-11-01

While extensive analyses have been conducted to test for, no formal analyses have been conducted to test against, the importance of candidate genes as putative QTLs using random population samples. Previously, we developed an LOD score exclusion mapping approach for candidate genes for complex diseases. Here, we extend this LOD score approach for exclusion analyses of candidate genes for quantitative traits. Under this approach, specific genetic effects (as reflected by heritability) and inheritance models at candidate QTLs can be analyzed and if an LOD score is < or = -2.0, the locus can be excluded from having a heritability larger than that specified. Simulations show that this approach has high power to exclude a candidate gene from having moderate genetic effects if it is not a QTL and is robust to population admixture. Our exclusion analysis complements association analysis for candidate genes as putative QTLs in random population samples. The approach is applied to test the importance of Vitamin D receptor (VDR) gene as a potential QTL underlying the variation of bone mass, an important determinant of osteoporosis.

Association of funding and conclusions in randomized drug trials: a reflection of treatment effect or adverse events?

PubMed

Als-Nielsen, Bodil; Chen, Wendong; Gluud, Christian; Kjaergard, Lise L

2003-08-20

Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions. To explore whether the association between funding and conclusions in randomized drug trials reflects treatment effects or adverse events. Observational study of 370 randomized drug trials included in meta-analyses from Cochrane reviews selected from the Cochrane Library, May 2001. From a random sample of 167 Cochrane reviews, 25 contained eligible meta-analyses (assessed a binary outcome; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment). The primary binary outcome from each meta-analysis was considered the primary outcome for all trials included in each meta-analysis. The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect, adverse events, and additional confounding factors (methodological quality, control intervention, sample size, publication year, and place of publication). Conclusions in trials, classified into whether the experimental drug was recommended as the treatment of choice or not. The experimental drug was recommended as treatment of choice in 16% of trials funded by nonprofit organizations, 30% of trials not reporting funding, 35% of trials funded by both nonprofit and for-profit organizations, and 51% of trials funded by for-profit organizations (P<.001; chi2 test). Logistic regression analyses indicated that funding, treatment effect, and double blinding were the only significant predictors of conclusions. Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice (odds ratio, 5.3; 95% confidence interval, 2.0-14.4) compared with trials funded by nonprofit organizations. This association did not appear to reflect treatment effect or adverse events. Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results. Readers should carefully evaluate whether conclusions in randomized trials are supported by data.

Clinical effects of pre-adjusted edgewise orthodontic brackets: a systematic review and meta-analysis.

PubMed

Papageorgiou, Spyridon N; Konstantinidis, Ioannis; Papadopoulou, Konstantina; Jäger, Andreas; Bourauel, Christoph

2014-06-01

Fixed-appliance treatment is a major part of orthodontic treatment, but clinical evidence remains scarce. Objective of this systematic review was to investigate how the therapeutic effects and side-effects of brackets used during the fixed-appliance orthodontic treatment are affected by their characteristics. SEARCH METHODS AND SELECTION CRITERIA: We searched MEDLINE and 18 other databases through April 2012 without restrictions for randomized controlled trials and quasi-randomized controlled trials investigating any bracket characteristic. After duplicate selection and extraction procedures, risk of bias was assessed also in duplicate according to Cochrane guidelines and quality of evidence according to the Grades of Recommendation. Assessment, Development and Evaluation approach. Random-effects meta-analyses, subgroup analyses, and sensitivity analyses were performed with the corresponding 95 per cent confidence intervals (CI) and 95 per cent prediction intervals (PI). We included 25 trials on 1321 patients, with most comparing self-ligated (SL) and conventional brackets. Based on the meta-analyses, the duration of orthodontic treatment was on average 2.01 months longer among patients with SL brackets (95 per cent CI: 0.45 to 3.57). The 95 per cent PIs for a future trial indicated that the difference could be considerable (-1.46 to 5.47 months). Treatment characteristics, outcomes, and side-effects were clinically similar between SL and conventional brackets. For most bracket characteristics, evidence is insufficient. Some meta-analyses included trials with high risk of bias, but sensitivity analyses indicated robustness. Based on existing evidence, no clinical recommendation can be made regarding the bracket material or different ligation modules. For SL brackets, no conclusive benefits could be proven, while their use was associated with longer treatment durations.

Concordance of Results from Randomized and Observational Analyses within the Same Study: A Re-Analysis of the Women's Health Initiative Limited-Access Dataset.

PubMed

Bolland, Mark J; Grey, Andrew; Gamble, Greg D; Reid, Ian R

2015-01-01

Observational studies (OS) and randomized controlled trials (RCTs) often report discordant results. In the Women's Health Initiative Calcium and Vitamin D (WHI CaD) RCT, women were randomly assigned to CaD or placebo, but were permitted to use personal calcium and vitamin D supplements, creating a unique opportunity to compare results from randomized and observational analyses within the same study. WHI CaD was a 7-year RCT of 1g calcium/400IU vitamin D daily in 36,282 post-menopausal women. We assessed the effects of CaD on cardiovascular events, death, cancer and fracture in a randomized design- comparing CaD with placebo in 43% of women not using personal calcium or vitamin D supplements- and in a observational design- comparing women in the placebo group (44%) using personal calcium and vitamin D supplements with non-users. Incidence was assessed using Cox proportional hazards models, and results from the two study designs deemed concordant if the absolute difference in hazard ratios was ≤0.15. We also compared results from WHI CaD to those from the WHI Observational Study(WHI OS), which used similar methodology for analyses and recruited from the same population. In WHI CaD, for myocardial infarction and stroke, results of unadjusted and 6/8 covariate-controlled observational analyses (age-adjusted, multivariate-adjusted, propensity-adjusted, propensity-matched) were not concordant with the randomized design results. For death, hip and total fracture, colorectal and total cancer, unadjusted and covariate-controlled observational results were concordant with randomized results. For breast cancer, unadjusted and age-adjusted observational results were concordant with randomized results, but only 1/3 other covariate-controlled observational results were concordant with randomized results. Multivariate-adjusted results from WHI OS were concordant with randomized WHI CaD results for only 4/8 endpoints. Results of randomized analyses in WHI CaD were concordant with observational analyses for 5/8 endpoints in WHI CaD and 4/8 endpoints in WHI OS.

Concordance of Results from Randomized and Observational Analyses within the Same Study: A Re-Analysis of the Women’s Health Initiative Limited-Access Dataset

PubMed Central

Bolland, Mark J.; Grey, Andrew; Gamble, Greg D.; Reid, Ian R.

2015-01-01

Background Observational studies (OS) and randomized controlled trials (RCTs) often report discordant results. In the Women’s Health Initiative Calcium and Vitamin D (WHI CaD) RCT, women were randomly assigned to CaD or placebo, but were permitted to use personal calcium and vitamin D supplements, creating a unique opportunity to compare results from randomized and observational analyses within the same study. Methods WHI CaD was a 7-year RCT of 1g calcium/400IU vitamin D daily in 36,282 post-menopausal women. We assessed the effects of CaD on cardiovascular events, death, cancer and fracture in a randomized design- comparing CaD with placebo in 43% of women not using personal calcium or vitamin D supplements- and in a observational design- comparing women in the placebo group (44%) using personal calcium and vitamin D supplements with non-users. Incidence was assessed using Cox proportional hazards models, and results from the two study designs deemed concordant if the absolute difference in hazard ratios was ≤0.15. We also compared results from WHI CaD to those from the WHI Observational Study(WHI OS), which used similar methodology for analyses and recruited from the same population. Results In WHI CaD, for myocardial infarction and stroke, results of unadjusted and 6/8 covariate-controlled observational analyses (age-adjusted, multivariate-adjusted, propensity-adjusted, propensity-matched) were not concordant with the randomized design results. For death, hip and total fracture, colorectal and total cancer, unadjusted and covariate-controlled observational results were concordant with randomized results. For breast cancer, unadjusted and age-adjusted observational results were concordant with randomized results, but only 1/3 other covariate-controlled observational results were concordant with randomized results. Multivariate-adjusted results from WHI OS were concordant with randomized WHI CaD results for only 4/8 endpoints. Conclusions Results of randomized analyses in WHI CaD were concordant with observational analyses for 5/8 endpoints in WHI CaD and 4/8 endpoints in WHI OS. PMID:26440516

A General Framework for Power Analysis to Detect the Moderator Effects in Two- and Three-Level Cluster Randomized Trials

ERIC Educational Resources Information Center

Dong, Nianbo; Spybrook, Jessaca; Kelcey, Ben

2016-01-01

The purpose of this study is to propose a general framework for power analyses to detect the moderator effects in two- and three-level cluster randomized trials (CRTs). The study specifically aims to: (1) develop the statistical formulations for calculating statistical power, minimum detectable effect size (MDES) and its confidence interval to…

Determination of genotoxic effects of boron and zinc on Zea mays using protein and random amplification of polymorphic DNA analyses.

PubMed

Erturk, Filiz Aygun; Nardemir, Gokce; Hilal, A Y; Arslan, Esra; Agar, Guleray

2015-11-01

In this research, we aimed to determine genotoxic effects of boron (B) and zinc (Zn) on Zea mays by using total soluble protein content and random amplification of polymorphic DNA (RAPD) analyses. For the RAPD analysis, 16 RAPD primers were found to produce unique polymorphic band profiles on treated maize seedlings. With increased Zn and B concentrations, increased polymorphism rate was observed, while genomic template stability and total soluble protein content decreased. The treatment with Zn was more effective than that of B groups on the levels of total proteins. The obtained results from this study revealed that the total soluble protein levels and RAPD profiles were performed as endpoints of genotoxicity and these analyses can offer useful biomarker assays for the evaluation of genotoxic effects on Zn and B polluted plants. © The Author(s) 2013.

Bayesian statistical inference enhances the interpretation of contemporary randomized controlled trials.

PubMed

Wijeysundera, Duminda N; Austin, Peter C; Hux, Janet E; Beattie, W Scott; Laupacis, Andreas

2009-01-01

Randomized trials generally use "frequentist" statistics based on P-values and 95% confidence intervals. Frequentist methods have limitations that might be overcome, in part, by Bayesian inference. To illustrate these advantages, we re-analyzed randomized trials published in four general medical journals during 2004. We used Medline to identify randomized superiority trials with two parallel arms, individual-level randomization and dichotomous or time-to-event primary outcomes. Studies with P<0.05 in favor of the intervention were deemed "positive"; otherwise, they were "negative." We used several prior distributions and exact conjugate analyses to calculate Bayesian posterior probabilities for clinically relevant effects. Of 88 included studies, 39 were positive using a frequentist analysis. Although the Bayesian posterior probabilities of any benefit (relative risk or hazard ratio<1) were high in positive studies, these probabilities were lower and variable for larger benefits. The positive studies had only moderate probabilities for exceeding the effects that were assumed for calculating the sample size. By comparison, there were moderate probabilities of any benefit in negative studies. Bayesian and frequentist analyses complement each other when interpreting the results of randomized trials. Future reports of randomized trials should include both.

Accounting for Heterogeneity in Relative Treatment Effects for Use in Cost-Effectiveness Models and Value-of-Information Analyses

PubMed Central

Soares, Marta O.; Palmer, Stephen; Ades, Anthony E.; Harrison, David; Shankar-Hari, Manu; Rowan, Kathy M.

2015-01-01

Cost-effectiveness analysis (CEA) models are routinely used to inform health care policy. Key model inputs include relative effectiveness of competing treatments, typically informed by meta-analysis. Heterogeneity is ubiquitous in meta-analysis, and random effects models are usually used when there is variability in effects across studies. In the absence of observed treatment effect modifiers, various summaries from the random effects distribution (random effects mean, predictive distribution, random effects distribution, or study-specific estimate [shrunken or independent of other studies]) can be used depending on the relationship between the setting for the decision (population characteristics, treatment definitions, and other contextual factors) and the included studies. If covariates have been measured that could potentially explain the heterogeneity, then these can be included in a meta-regression model. We describe how covariates can be included in a network meta-analysis model and how the output from such an analysis can be used in a CEA model. We outline a model selection procedure to help choose between competing models and stress the importance of clinical input. We illustrate the approach with a health technology assessment of intravenous immunoglobulin for the management of adult patients with severe sepsis in an intensive care setting, which exemplifies how risk of bias information can be incorporated into CEA models. We show that the results of the CEA and value-of-information analyses are sensitive to the model and highlight the importance of sensitivity analyses when conducting CEA in the presence of heterogeneity. The methods presented extend naturally to heterogeneity in other model inputs, such as baseline risk. PMID:25712447

Accounting for Heterogeneity in Relative Treatment Effects for Use in Cost-Effectiveness Models and Value-of-Information Analyses.

PubMed

Welton, Nicky J; Soares, Marta O; Palmer, Stephen; Ades, Anthony E; Harrison, David; Shankar-Hari, Manu; Rowan, Kathy M

2015-07-01

Cost-effectiveness analysis (CEA) models are routinely used to inform health care policy. Key model inputs include relative effectiveness of competing treatments, typically informed by meta-analysis. Heterogeneity is ubiquitous in meta-analysis, and random effects models are usually used when there is variability in effects across studies. In the absence of observed treatment effect modifiers, various summaries from the random effects distribution (random effects mean, predictive distribution, random effects distribution, or study-specific estimate [shrunken or independent of other studies]) can be used depending on the relationship between the setting for the decision (population characteristics, treatment definitions, and other contextual factors) and the included studies. If covariates have been measured that could potentially explain the heterogeneity, then these can be included in a meta-regression model. We describe how covariates can be included in a network meta-analysis model and how the output from such an analysis can be used in a CEA model. We outline a model selection procedure to help choose between competing models and stress the importance of clinical input. We illustrate the approach with a health technology assessment of intravenous immunoglobulin for the management of adult patients with severe sepsis in an intensive care setting, which exemplifies how risk of bias information can be incorporated into CEA models. We show that the results of the CEA and value-of-information analyses are sensitive to the model and highlight the importance of sensitivity analyses when conducting CEA in the presence of heterogeneity. The methods presented extend naturally to heterogeneity in other model inputs, such as baseline risk. © The Author(s) 2015.

Quantifying, displaying and accounting for heterogeneity in the meta-analysis of RCTs using standard and generalised Q statistics

PubMed Central

2011-01-01

Background Clinical researchers have often preferred to use a fixed effects model for the primary interpretation of a meta-analysis. Heterogeneity is usually assessed via the well known Q and I2 statistics, along with the random effects estimate they imply. In recent years, alternative methods for quantifying heterogeneity have been proposed, that are based on a 'generalised' Q statistic. Methods We review 18 IPD meta-analyses of RCTs into treatments for cancer, in order to quantify the amount of heterogeneity present and also to discuss practical methods for explaining heterogeneity. Results Differing results were obtained when the standard Q and I2 statistics were used to test for the presence of heterogeneity. The two meta-analyses with the largest amount of heterogeneity were investigated further, and on inspection the straightforward application of a random effects model was not deemed appropriate. Compared to the standard Q statistic, the generalised Q statistic provided a more accurate platform for estimating the amount of heterogeneity in the 18 meta-analyses. Conclusions Explaining heterogeneity via the pre-specification of trial subgroups, graphical diagnostic tools and sensitivity analyses produced a more desirable outcome than an automatic application of the random effects model. Generalised Q statistic methods for quantifying and adjusting for heterogeneity should be incorporated as standard into statistical software. Software is provided to help achieve this aim. PMID:21473747

Micro-Randomized Trials: An Experimental Design for Developing Just-in-Time Adaptive Interventions

PubMed Central

Klasnja, Predrag; Hekler, Eric B.; Shiffman, Saul; Boruvka, Audrey; Almirall, Daniel; Tewari, Ambuj; Murphy, Susan A.

2015-01-01

Objective This paper presents an experimental design, the micro-randomized trial, developed to support optimization of just-in-time adaptive interventions (JITAIs). JITAIs are mHealth technologies that aim to deliver the right intervention components at the right times and locations to optimally support individuals’ health behaviors. Micro-randomized trials offer a way to optimize such interventions by enabling modeling of causal effects and time-varying effect moderation for individual intervention components within a JITAI. Methods The paper describes the micro-randomized trial design, enumerates research questions that this experimental design can help answer, and provides an overview of the data analyses that can be used to assess the causal effects of studied intervention components and investigate time-varying moderation of those effects. Results Micro-randomized trials enable causal modeling of proximal effects of the randomized intervention components and assessment of time-varying moderation of those effects. Conclusions Micro-randomized trials can help researchers understand whether their interventions are having intended effects, when and for whom they are effective, and what factors moderate the interventions’ effects, enabling creation of more effective JITAIs. PMID:26651463

Random-effects linear modeling and sample size tables for two special crossover designs of average bioequivalence studies: the four-period, two-sequence, two-formulation and six-period, three-sequence, three-formulation designs.

PubMed

Diaz, Francisco J; Berg, Michel J; Krebill, Ron; Welty, Timothy; Gidal, Barry E; Alloway, Rita; Privitera, Michael

2013-12-01

Due to concern and debate in the epilepsy medical community and to the current interest of the US Food and Drug Administration (FDA) in revising approaches to the approval of generic drugs, the FDA is currently supporting ongoing bioequivalence studies of antiepileptic drugs, the EQUIGEN studies. During the design of these crossover studies, the researchers could not find commercial or non-commercial statistical software that quickly allowed computation of sample sizes for their designs, particularly software implementing the FDA requirement of using random-effects linear models for the analyses of bioequivalence studies. This article presents tables for sample-size evaluations of average bioequivalence studies based on the two crossover designs used in the EQUIGEN studies: the four-period, two-sequence, two-formulation design, and the six-period, three-sequence, three-formulation design. Sample-size computations assume that random-effects linear models are used in bioequivalence analyses with crossover designs. Random-effects linear models have been traditionally viewed by many pharmacologists and clinical researchers as just mathematical devices to analyze repeated-measures data. In contrast, a modern view of these models attributes an important mathematical role in theoretical formulations in personalized medicine to them, because these models not only have parameters that represent average patients, but also have parameters that represent individual patients. Moreover, the notation and language of random-effects linear models have evolved over the years. Thus, another goal of this article is to provide a presentation of the statistical modeling of data from bioequivalence studies that highlights the modern view of these models, with special emphasis on power analyses and sample-size computations.

Environmental risk factors and Parkinson's disease: An umbrella review of meta-analyses.

PubMed

Bellou, Vanesa; Belbasis, Lazaros; Tzoulaki, Ioanna; Evangelou, Evangelos; Ioannidis, John P A

2016-02-01

Parkinson's disease is a neurological disorder with complex pathogenesis implicating both environmental and genetic factors. We aimed to summarise the environmental risk factors that have been studied for potential association with Parkinson's disease, assess the presence of diverse biases, and identify the risk factors with the strongest support. We searched PubMed from inception to September 18, 2015, to identify systematic reviews and meta-analyses of observational studies that examined associations between environmental factors and Parkinson's disease. For each meta-analysis we estimated the summary effect size by random-effects and fixed-effects models, the 95% confidence interval and the 95% prediction interval. We estimated the between-study heterogeneity expressed by I(2), evidence of small-study effects and evidence of excess significance bias. Overall, 75 unique meta-analyses on different risk factors for Parkinson's disease were examined, covering diverse biomarkers, dietary factors, drugs, medical history or comorbid diseases, exposure to toxic environmental agents and habits. 21 of 75 meta-analyses had results that were significant at p < 0.001 by random-effects. Evidence for an association was convincing (more than 1000 cases, p < 10(-6) by random-effects, not large heterogeneity, 95% prediction interval excluding the null value and absence of hints for small-study effects and excess significance bias) for constipation, and physical activity. Many environmental factors have substantial evidence of association with Parkinson's disease, but several, perhaps most, of them may reflect reverse causation, residual confounding, information bias, sponsor conflicts or other caveats. Copyright © 2016. Published by Elsevier Ltd.

Thrombectomy for ischemic stroke: meta-analyses of recurrent strokes, vasospasms, and subarachnoid hemorrhages.

PubMed

Emprechtinger, Robert; Piso, Brigitte; Ringleb, Peter A

2017-03-01

Mechanical thrombectomy with stent retrievers is an effective treatment for patients with ischemic stroke. Results of recent meta-analyses report that the treatment is safe. However, the endpoints recurrent stroke, vasospasms, and subarachnoid hemorrhage have not been evaluated sufficiently. Hence, we extracted data on these outcomes from the five recent thrombectomy trials (MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA published in 2015). Subsequently, we conducted meta-analyses for each outcome. We report the results of the fixed, as well as the random effects model. Three studies reported data on recurrent strokes. While the results did not reach statistical significance in the random effects model (despite a three times elevated risk), the fixed effects model revealed a significantly higher rate of recurrent strokes after thrombectomy. Four studies reported data on subarachnoid hemorrhage. The higher pooled rates in the intervention groups were statistically significant in both, the fixed and the random effects model. One study reported on vasospasms. We recorded 14 events in the intervention group and none in the control group. The efficacy of mechanical thrombectomy is not questioned, yet our results indicate an increased risk for recurrent strokes, subarachnoid hemorrhage, and vasospasms post-treatment. Therefore, we strongly recommend a thoroughly surveillance, concerning these adverse events in future clinical trials and routine registries.

Coordinate based random effect size meta-analysis of neuroimaging studies.

PubMed

Tench, C R; Tanasescu, Radu; Constantinescu, C S; Auer, D P; Cottam, W J

2017-06-01

Low power in neuroimaging studies can make them difficult to interpret, and Coordinate based meta-analysis (CBMA) may go some way to mitigating this issue. CBMA has been used in many analyses to detect where published functional MRI or voxel-based morphometry studies testing similar hypotheses report significant summary results (coordinates) consistently. Only the reported coordinates and possibly t statistics are analysed, and statistical significance of clusters is determined by coordinate density. Here a method of performing coordinate based random effect size meta-analysis and meta-regression is introduced. The algorithm (ClusterZ) analyses both coordinates and reported t statistic or Z score, standardised by the number of subjects. Statistical significance is determined not by coordinate density, but by a random effects meta-analyses of reported effects performed cluster-wise using standard statistical methods and taking account of censoring inherent in the published summary results. Type 1 error control is achieved using the false cluster discovery rate (FCDR), which is based on the false discovery rate. This controls both the family wise error rate under the null hypothesis that coordinates are randomly drawn from a standard stereotaxic space, and the proportion of significant clusters that are expected under the null. Such control is necessary to avoid propagating and even amplifying the very issues motivating the meta-analysis in the first place. ClusterZ is demonstrated on both numerically simulated data and on real data from reports of grey matter loss in multiple sclerosis (MS) and syndromes suggestive of MS, and of painful stimulus in healthy controls. The software implementation is available to download and use freely. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of different preservation methods on inter simple sequence repeat (ISSR) and random amplified polymorphic DNA (RAPD) molecular markers in botanic samples.

PubMed

Wang, Xiaolong; Li, Lin; Zhao, Jiaxin; Li, Fangliang; Guo, Wei; Chen, Xia

2017-04-01

To evaluate the effects of different preservation methods (stored in a -20°C ice chest, preserved in liquid nitrogen and dried in silica gel) on inter simple sequence repeat (ISSR) or random amplified polymorphic DNA (RAPD) analyses in various botanical specimens (including broad-leaved plants, needle-leaved plants and succulent plants) for different times (three weeks and three years), we used a statistical analysis based on the number of bands, genetic index and cluster analysis. The results demonstrate that methods used to preserve samples can provide sufficient amounts of genomic DNA for ISSR and RAPD analyses; however, the effect of different preservation methods on these analyses vary significantly, and the preservation time has little effect on these analyses. Our results provide a reference for researchers to select the most suitable preservation method depending on their study subject for the analysis of molecular markers based on genomic DNA. Copyright © 2017 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

Effect of packing method on the randomness of disc packings

NASA Astrophysics Data System (ADS)

Zhang, Z. P.; Yu, A. B.; Oakeshott, R. B. S.

1996-06-01

The randomness of disc packings, generated by random sequential adsorption (RSA), random packing under gravity (RPG) and Mason packing (MP) which gives a packing density close to that of the RSA packing, has been analysed, based on the Delaunay tessellation, and is evaluated at two levels, i.e. the randomness at individual subunit level which relates to the construction of a triangle from a given edge length distribution and the randomness at network level which relates to the connection between triangles from a given triangle frequency distribution. The Delaunay tessellation itself is also analysed and its almost perfect randomness at the two levels is demonstrated, which verifies the proposed approach and provides a random reference system for the present analysis. It is found that (i) the construction of a triangle subunit is not random for the RSA, MP and RPG packings, with the degree of randomness decreasing from the RSA to MP and then to RPG packing; (ii) the connection of triangular subunits in the network is almost perfectly random for the RSA packing, acceptable for the MP packing and not good for the RPG packing. Packing method is an important factor governing the randomness of disc packings.

Meta-analysis of two studies in the presence of heterogeneity with applications in rare diseases.

PubMed

Friede, Tim; Röver, Christian; Wandel, Simon; Neuenschwander, Beat

2017-07-01

Random-effects meta-analyses are used to combine evidence of treatment effects from multiple studies. Since treatment effects may vary across trials due to differences in study characteristics, heterogeneity in treatment effects between studies must be accounted for to achieve valid inference. The standard model for random-effects meta-analysis assumes approximately normal effect estimates and a normal random-effects model. However, standard methods based on this model ignore the uncertainty in estimating the between-trial heterogeneity. In the special setting of only two studies and in the presence of heterogeneity, we investigate here alternatives such as the Hartung-Knapp-Sidik-Jonkman method (HKSJ), the modified Knapp-Hartung method (mKH, a variation of the HKSJ method) and Bayesian random-effects meta-analyses with priors covering plausible heterogeneity values; R code to reproduce the examples is presented in an appendix. The properties of these methods are assessed by applying them to five examples from various rare diseases and by a simulation study. Whereas the standard method based on normal quantiles has poor coverage, the HKSJ and mKH generally lead to very long, and therefore inconclusive, confidence intervals. The Bayesian intervals on the whole show satisfying properties and offer a reasonable compromise between these two extremes. © 2016 The Authors. Biometrical Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Anomalous Anticipatory Responses in Networked Random Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nelson, Roger D.; Bancel, Peter A.

2006-10-16

We examine an 8-year archive of synchronized, parallel time series of random data from a world spanning network of physical random event generators (REGs). The archive is a publicly accessible matrix of normally distributed 200-bit sums recorded at 1 Hz which extends from August 1998 to the present. The primary question is whether these data show non-random structure associated with major events such as natural or man-made disasters, terrible accidents, or grand celebrations. Secondarily, we examine the time course of apparently correlated responses. Statistical analyses of the data reveal consistent evidence that events which strongly affect people engender small butmore » significant effects. These include suggestions of anticipatory responses in some cases, leading to a series of specialized analyses to assess possible non-random structure preceding precisely timed events. A focused examination of data collected around the time of earthquakes with Richter magnitude 6 and greater reveals non-random structure with a number of intriguing, potentially important features. Anomalous effects in the REG data are seen only when the corresponding earthquakes occur in populated areas. No structure is found if they occur in the oceans. We infer that an important contributor to the effect is the relevance of the earthquake to humans. Epoch averaging reveals evidence for changes in the data some hours prior to the main temblor, suggestive of reverse causation.« less

Mediational Analyses of the Effects of Responsive Teaching on the Developmental Functioning of Preschool Children with Disabilities

ERIC Educational Resources Information Center

Karaaslan, Ozcan; Mahoney, Gerald

2015-01-01

Mediational analyses were conducted with data from two small randomized control trials of the Responsive Teaching (RT) parent-mediated developmental intervention which used nearly identical intervention and control procedures. The purpose of these analyses was to determine whether or how the changes in maternal responsiveness and children's…

Systematic overview and critical appraisal of meta-analyses of interventions in intensive care medicine.

PubMed

Koster, T M; Wetterslev, J; Gluud, C; Keus, F; van der Horst, I C C

2018-05-24

Meta-analysed intervention effect estimates are perceived to represent the highest level of evidence. However, such effects and the randomized clinical trials which are included in them need critical appraisal before the effects can be trusted. Critical appraisal of a predefined set of all meta-analyses on interventions in intensive care medicine to assess their quality and assessed the risks of bias in those meta-analyses having the best quality. We conducted a systematic search to select all meta-analyses of randomized clinical trials on interventions used in intensive care medicine. Selected meta-analyses were critically appraised for basic scientific criteria, (1) presence of an available protocol, (2) report of a full search strategy, and (3) use of any bias risk assessment of included trials. All meta-analyses which qualified these criteria were scrutinized by full "Risk of Bias in Systematic Reviews" ROBIS evaluation of 4 domains of risks of bias, and a "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" PRISMA evaluation. We identified 467 meta-analyses. A total of 56 meta-analyses complied with these basic scientific criteria. We scrutinized the risks of bias in the 56 meta-analyses by full ROBIS evaluation and a PRISMA evaluation. Only 4 meta-analyses scored low risk of bias in all the 4 ROBIS domains and 41 meta-analyses reported all 27 items of the PRISMA checklist. In contrast with what might be perceived as the highest level of evidence only 0.9% of all meta-analyses were judged to have overall low risk of bias. © 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

The Number of Patients and Events Required to Limit the Risk of Overestimation of Intervention Effects in Meta-Analysis—A Simulation Study

PubMed Central

Thorlund, Kristian; Imberger, Georgina; Walsh, Michael; Chu, Rong; Gluud, Christian; Wetterslev, Jørn; Guyatt, Gordon; Devereaux, Philip J.; Thabane, Lehana

2011-01-01

Background Meta-analyses including a limited number of patients and events are prone to yield overestimated intervention effect estimates. While many assume bias is the cause of overestimation, theoretical considerations suggest that random error may be an equal or more frequent cause. The independent impact of random error on meta-analyzed intervention effects has not previously been explored. It has been suggested that surpassing the optimal information size (i.e., the required meta-analysis sample size) provides sufficient protection against overestimation due to random error, but this claim has not yet been validated. Methods We simulated a comprehensive array of meta-analysis scenarios where no intervention effect existed (i.e., relative risk reduction (RRR) = 0%) or where a small but possibly unimportant effect existed (RRR = 10%). We constructed different scenarios by varying the control group risk, the degree of heterogeneity, and the distribution of trial sample sizes. For each scenario, we calculated the probability of observing overestimates of RRR>20% and RRR>30% for each cumulative 500 patients and 50 events. We calculated the cumulative number of patients and events required to reduce the probability of overestimation of intervention effect to 10%, 5%, and 1%. We calculated the optimal information size for each of the simulated scenarios and explored whether meta-analyses that surpassed their optimal information size had sufficient protection against overestimation of intervention effects due to random error. Results The risk of overestimation of intervention effects was usually high when the number of patients and events was small and this risk decreased exponentially over time as the number of patients and events increased. The number of patients and events required to limit the risk of overestimation depended considerably on the underlying simulation settings. Surpassing the optimal information size generally provided sufficient protection against overestimation. Conclusions Random errors are a frequent cause of overestimation of intervention effects in meta-analyses. Surpassing the optimal information size will provide sufficient protection against overestimation. PMID:22028777

Boundary element analyses for sound transmission loss of panels.

PubMed

Zhou, Ran; Crocker, Malcolm J

2010-02-01

The sound transmission characteristics of an aluminum panel and two composite sandwich panels were investigated by using two boundary element analyses. The effect of air loading on the structural behavior of the panels is included in one boundary element analysis, by using a light-fluid approximation for the eigenmode series to evaluate the structural response. In the other boundary element analysis, the air loading is treated as an added mass. The effect of the modal energy loss factor on the sound transmission loss of the panels was investigated. Both boundary element analyses were used to study the sound transmission loss of symmetric sandwich panels excited by a random incidence acoustic field. A classical wave impedance analysis was also used to make sound transmission loss predictions for the two foam-filled honeycomb sandwich panels. Comparisons between predictions of sound transmission loss for the two foam-filled honeycomb sandwich panels excited by a random incidence acoustic field obtained from the wave impedance analysis, the two boundary element analyses, and experimental measurements are presented.

Testing self-regulation interventions to increase walking using factorial randomized N-of-1 trials.

PubMed

Sniehotta, Falko F; Presseau, Justin; Hobbs, Nicola; Araújo-Soares, Vera

2012-11-01

To investigate the suitability of N-of-1 randomized controlled trials (RCTs) as a means of testing the effectiveness of behavior change techniques based on self-regulation theory (goal setting and self-monitoring) for promoting walking in healthy adult volunteers. A series of N-of-1 RCTs in 10 normal and overweight adults ages 19-67 (M = 36.9 years). We randomly allocated 60 days within each individual to text message-prompted daily goal-setting and/or self-monitoring interventions in accordance with a 2 (step-count goal prompt vs. alternative goal prompt) × 2 (self-monitoring: open vs. blinded Omron-HJ-113-E pedometer) factorial design. Aggregated data were analyzed using random intercept multilevel models. Single cases were analyzed individually. The primary outcome was daily pedometer step counts over 60 days. Single-case analyses showed that 4 participants significantly increased walking: 2 on self-monitoring days and 2 on goal-setting days, compared with control days. Six participants did not benefit from the interventions. In aggregated analyses, mean step counts were higher on goal-setting days (8,499.9 vs. 7,956.3) and on self-monitoring days (8,630.3 vs. 7,825.9). Multilevel analyses showed a significant effect of the self-monitoring condition (p = .01), the goal-setting condition approached significance (p = .08), and there was a small linear increase in walking over time (p = .03). N-of-1 randomized trials are a suitable means to test behavioral interventions in individual participants.

Breeding value accuracy estimates for growth traits using random regression and multi-trait models in Nelore cattle.

PubMed

Boligon, A A; Baldi, F; Mercadante, M E Z; Lobo, R B; Pereira, R J; Albuquerque, L G

2011-06-28

We quantified the potential increase in accuracy of expected breeding value for weights of Nelore cattle, from birth to mature age, using multi-trait and random regression models on Legendre polynomials and B-spline functions. A total of 87,712 weight records from 8144 females were used, recorded every three months from birth to mature age from the Nelore Brazil Program. For random regression analyses, all female weight records from birth to eight years of age (data set I) were considered. From this general data set, a subset was created (data set II), which included only nine weight records: at birth, weaning, 365 and 550 days of age, and 2, 3, 4, 5, and 6 years of age. Data set II was analyzed using random regression and multi-trait models. The model of analysis included the contemporary group as fixed effects and age of dam as a linear and quadratic covariable. In the random regression analyses, average growth trends were modeled using a cubic regression on orthogonal polynomials of age. Residual variances were modeled by a step function with five classes. Legendre polynomials of fourth and sixth order were utilized to model the direct genetic and animal permanent environmental effects, respectively, while third-order Legendre polynomials were considered for maternal genetic and maternal permanent environmental effects. Quadratic polynomials were applied to model all random effects in random regression models on B-spline functions. Direct genetic and animal permanent environmental effects were modeled using three segments or five coefficients, and genetic maternal and maternal permanent environmental effects were modeled with one segment or three coefficients in the random regression models on B-spline functions. For both data sets (I and II), animals ranked differently according to expected breeding value obtained by random regression or multi-trait models. With random regression models, the highest gains in accuracy were obtained at ages with a low number of weight records. The results indicate that random regression models provide more accurate expected breeding values than the traditionally finite multi-trait models. Thus, higher genetic responses are expected for beef cattle growth traits by replacing a multi-trait model with random regression models for genetic evaluation. B-spline functions could be applied as an alternative to Legendre polynomials to model covariance functions for weights from birth to mature age.

Prenatal vitamin D supplementation reduces risk of asthma/recurrent wheeze in early childhood: A combined analysis of two randomized controlled trials

PubMed Central

Wolsk, Helene M.; Chawes, Bo L.; Litonjua, Augusto A.; Hollis, Bruce W.; Waage, Johannes; Stokholm, Jakob; Bønnelykke, Klaus; Bisgaard, Hans

2017-01-01

Background We recently published two independent randomized controlled trials of vitamin D supplementation during pregnancy, both indicating a >20% reduced risk of asthma/recurrent wheeze in the offspring by 3 years of age. However, neither reached statistical significance. Objective To perform a combined analysis of the two trials and investigate whether maternal 25-hydroxy-vitamin D (25(OH)D) level at trial entry modified the intervention effect. Methods VDAART (N = 806) and COPSAC2010. (N = 581) randomized pregnant women to daily high-dose vitamin D3 (4,000 IU/d and 2,400 IU/d, respectively) or placebo. All women also received a prenatal vitamin containing 400 IU/d vitamin D3. The primary outcome was asthma/recurrent wheeze from 0-3yrs. Secondary end-points were specific IgE, total IgE, eczema and lower respiratory tract infections (LRTI). We conducted random effects combined analyses of the treatment effect, individual patient data (IPD) meta-analyses, and analyses stratified by 25(OH)D level at study entry. Results The analysis showed a 25% reduced risk of asthma/recurrent wheeze at 0-3yrs: adjusted odds ratio (aOR) = 0.74 (95% CI, 0.57–0.96), p = 0.02. The effect was strongest among women with 25(OH)D level ≥30ng/ml at study entry: aOR = 0.54 (0.33–0.88), p = 0.01, whereas no significant effect was observed among women with 25(OH)D level <30ng/ml at study entry: aOR = 0.84 (0.62–1.15), p = 0.25. The IPD meta-analyses showed similar results. There was no effect on the secondary end-points. Conclusions This combined analysis shows that vitamin D supplementation during pregnancy results in a significant reduced risk of asthma/recurrent wheeze in the offspring, especially among women with 25(OH)D level ≥ 30 ng/ml at randomization, where the risk was almost halved. Future studies should examine the possibility of raising 25(OH)D levels to at least 30 ng/ml early in pregnancy or using higher doses than used in our studies. Trial registration COPSAC2010: ClinicalTrials.gov NCT00856947; VDAART: ClinicalTrials.gov NCT00920621 PMID:29077711

Impact of Contextual Factors on Prostate Cancer Risk and Outcomes

DTIC Science & Technology

2013-07-01

framework with random effects (“frailty models”) while the case-control analyses (Aim 4) will use multilevel unconditional logistic regression models...contextual-level SES on prostate cancer risk within racial/ethnic groups. The survival analyses (Aims 1-3) will utilize a proportional hazards regression

Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS): rationale and design for meta-analyses of individual patient data of randomized controlled trials that evaluate the effect of physical activity and psychosocial interventions on health-related quality of life in cancer survivors

PubMed Central

2013-01-01

Background Effective interventions to improve quality of life of cancer survivors are essential. Numerous randomized controlled trials have evaluated the effects of physical activity or psychosocial interventions on health-related quality of life of cancer survivors, with generally small sample sizes and modest effects. Better targeted interventions may result in larger effects. To realize such targeted interventions, we must determine which interventions that are presently available work for which patients, and what the underlying mechanisms are (that is, the moderators and mediators of physical activity and psychosocial interventions). Individual patient data meta-analysis has been described as the ‘gold standard’ of systematic review methodology. Instead of extracting aggregate data from study reports or from authors, the original research data are sought directly from the investigators. Individual patient data meta-analyses allow for adequate statistical analysis of intervention effects and moderators of such effects. Here, we report the rationale and design of the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) Consortium. The primary aim of POLARIS is 1) to conduct meta-analyses based on individual patient data to evaluate the effect of physical activity and psychosocial interventions on the health-related quality of life of cancer survivors; 2) to identify important demographic, clinical, personal, or intervention-related moderators of the effect; and 3) to build and validate clinical prediction models identifying the most relevant predictors of intervention success. Methods/Design We will invite investigators of randomized controlled trials that evaluate the effects of physical activity and/or psychosocial interventions on health-related quality of life compared with a wait-list, usual care or attention control group among adult cancer survivors to join the POLARIS consortium and share their data for use in pooled analyses that will address the proposed aims. We are in the process of identifying eligible randomized controlled trials through literature searches in four databases. To date, we have identified 132 eligible and unique trials. Discussion The POLARIS consortium will conduct the first individual patient data meta-analyses in order to generate evidence essential to targeting physical activity and psychosocial programs to the individual survivor’s characteristics, capabilities, and preferences. Registration PROSPERO: International prospective register of systematic reviews, CRD42013003805 PMID:24034173

The Transfer of Cognitive Speed of Processing Training to Older Adults’ Driving Mobility Across 5 Years

PubMed Central

Edwards, Jerri D.; O’Connor, Melissa L.; Ball, Karlene K.; Wadley, Virginia G.; Vance, David E.

2016-01-01

Objectives. Multilevel models assessed the effects of cognitive speed of processing training (SPT) on older adults’ self-reported driving using intention-to-treat (ITT, randomization to training or control conditions) and dosage (treatment-received via number of training sessions) analyses across 5 years. Method. Participants randomized to SPT (n = 598) were compared with those randomized to either the no-contact control (n = 598) or memory training, which served as an active control (n = 610). Driving mobility (frequency, exposure, and space) was assessed over time. Results. No significant effects were found within the ITT analyses. However, number of SPT sessions did affect driving mobility outcomes. In the full sample (N = 1,806), higher SPT doses were associated with maintained driving frequency as compared with both control groups, but no effects were found for driving exposure or space. Subsample analyses (n = 315) revealed that persons at-risk for mobility declines (i.e., poor initial processing speed) who received additional booster SPT sessions reported greater maintenance of both driving frequency and exposure over time as compared with the no-contact and active control groups. Discussion. These results and prior research indicate that cognitive SPT transfers to prolonged driving mobility among older adults. Future research should investigate the mechanisms behind transfer effects to real-world activities, such as driving. PMID:25878053

Bayesian hierarchical models for cost-effectiveness analyses that use data from cluster randomized trials.

PubMed

Grieve, Richard; Nixon, Richard; Thompson, Simon G

2010-01-01

Cost-effectiveness analyses (CEA) may be undertaken alongside cluster randomized trials (CRTs) where randomization is at the level of the cluster (for example, the hospital or primary care provider) rather than the individual. Costs (and outcomes) within clusters may be correlated so that the assumption made by standard bivariate regression models, that observations are independent, is incorrect. This study develops a flexible modeling framework to acknowledge the clustering in CEA that use CRTs. The authors extend previous Bayesian bivariate models for CEA of multicenter trials to recognize the specific form of clustering in CRTs. They develop new Bayesian hierarchical models (BHMs) that allow mean costs and outcomes, and also variances, to differ across clusters. They illustrate how each model can be applied using data from a large (1732 cases, 70 primary care providers) CRT evaluating alternative interventions for reducing postnatal depression. The analyses compare cost-effectiveness estimates from BHMs with standard bivariate regression models that ignore the data hierarchy. The BHMs show high levels of cost heterogeneity across clusters (intracluster correlation coefficient, 0.17). Compared with standard regression models, the BHMs yield substantially increased uncertainty surrounding the cost-effectiveness estimates, and altered point estimates. The authors conclude that ignoring clustering can lead to incorrect inferences. The BHMs that they present offer a flexible modeling framework that can be applied more generally to CEA that use CRTs.

Meta-analysis in evidence-based healthcare: a paradigm shift away from random effects is overdue.

PubMed

Doi, Suhail A R; Furuya-Kanamori, Luis; Thalib, Lukman; Barendregt, Jan J

2017-12-01

Each year up to 20 000 systematic reviews and meta-analyses are published whose results influence healthcare decisions, thus making the robustness and reliability of meta-analytic methods one of the world's top clinical and public health priorities. The evidence synthesis makes use of either fixed-effect or random-effects statistical methods. The fixed-effect method has largely been replaced by the random-effects method as heterogeneity of study effects led to poor error estimation. However, despite the widespread use and acceptance of the random-effects method to correct this, it too remains unsatisfactory and continues to suffer from defective error estimation, posing a serious threat to decision-making in evidence-based clinical and public health practice. We discuss here the problem with the random-effects approach and demonstrate that there exist better estimators under the fixed-effect model framework that can achieve optimal error estimation. We argue for an urgent return to the earlier framework with updates that address these problems and conclude that doing so can markedly improve the reliability of meta-analytical findings and thus decision-making in healthcare.

A general framework for the use of logistic regression models in meta-analysis.

PubMed

Simmonds, Mark C; Higgins, Julian Pt

2016-12-01

Where individual participant data are available for every randomised trial in a meta-analysis of dichotomous event outcomes, "one-stage" random-effects logistic regression models have been proposed as a way to analyse these data. Such models can also be used even when individual participant data are not available and we have only summary contingency table data. One benefit of this one-stage regression model over conventional meta-analysis methods is that it maximises the correct binomial likelihood for the data and so does not require the common assumption that effect estimates are normally distributed. A second benefit of using this model is that it may be applied, with only minor modification, in a range of meta-analytic scenarios, including meta-regression, network meta-analyses and meta-analyses of diagnostic test accuracy. This single model can potentially replace the variety of often complex methods used in these areas. This paper considers, with a range of meta-analysis examples, how random-effects logistic regression models may be used in a number of different types of meta-analyses. This one-stage approach is compared with widely used meta-analysis methods including Bayesian network meta-analysis and the bivariate and hierarchical summary receiver operating characteristic (ROC) models for meta-analyses of diagnostic test accuracy. © The Author(s) 2014.

A critical appraisal of the reporting quality of published randomized controlled trials in the fall injuries.

PubMed

Asghari Jafarabadi, Mohammad; Sadeghi-Bazrgani, Homayoun; Dianat, Iman

2018-06-01

To evaluate the quality of reporting in published randomized controlled trials (RTCs) in the field of fall injuries. The 188 RTCs published between 2001 and 2011, indexed in EMBASE and Medline databases were extracted through searching by appropriate keywords and EMTree classification terms. The evaluation trustworthiness was assured through parallel evaluations of two experts in epidemiology and biostatistics. About 40%-75% of papers had problems in reporting random allocation method, allocation concealment, random allocation implementation, blinding and similarity among groups, intention to treat and balancing benefits and harms. Moreover, at least 10% of papers inappropriately/not reported the design, protocol violations, sample size justification, subgroup/adjusted analyses, presenting flow diagram, drop outs, recruitment time, baseline data, suitable effect size on outcome, ancillary analyses, limitations and generalizability. Considering the shortcomings found and due to the importance of the RCTs for fall injury prevention programmes, their reporting quality should be improved.

Effect of expanding medicaid for parents on children's health insurance coverage: lessons from the Oregon experiment.

PubMed

DeVoe, Jennifer E; Marino, Miguel; Angier, Heather; O'Malley, Jean P; Crawford, Courtney; Nelson, Christine; Tillotson, Carrie J; Bailey, Steffani R; Gallia, Charles; Gold, Rachel

2015-01-01

In the United States, health insurance is not universal. Observational studies show an association between uninsured parents and children. This association persisted even after expansions in child-only public health insurance. Oregon's randomized Medicaid expansion for adults, known as the Oregon Experiment, created a rare opportunity to assess causality between parent and child coverage. To estimate the effect on a child's health insurance coverage status when (1) a parent randomly gains access to health insurance and (2) a parent obtains coverage. Oregon Experiment randomized natural experiment assessing the results of Oregon's 2008 Medicaid expansion. We used generalized estimating equation models to examine the longitudinal effect of a parent randomly selected to apply for Medicaid on their child's Medicaid or Children's Health Insurance Program (CHIP) coverage (intent-to-treat analyses). We used per-protocol analyses to understand the impact on children's coverage when a parent was randomly selected to apply for and obtained Medicaid. Participants included 14409 children aged 2 to 18 years whose parents participated in the Oregon Experiment. For intent-to-treat analyses, the date a parent was selected to apply for Medicaid was considered the date the child was exposed to the intervention. In per-protocol analyses, exposure was defined as whether a selected parent obtained Medicaid. Children's Medicaid or CHIP coverage, assessed monthly and in 6-month intervals relative to their parent's selection date. In the immediate period after selection, children whose parents were selected to apply significantly increased from 3830 (61.4%) to 4152 (66.6%) compared with a nonsignificant change from 5049 (61.8%) to 5044 (61.7%) for children whose parents were not selected to apply. Children whose parents were randomly selected to apply for Medicaid had 18% higher odds of being covered in the first 6 months after parent's selection compared with children whose parents were not selected (adjusted odds ratio [AOR]=1.18; 95% CI, 1.10-1.27). The effect remained significant during months 7 to 12 (AOR=1.11; 95% CI, 1.03-1.19); months 13 to 18 showed a positive but not significant effect (AOR=1.07; 95% CI, 0.99-1.14). Children whose parents were selected and obtained coverage had more than double the odds of having coverage compared with children whose parents were not selected and did not gain coverage (AOR=2.37; 95% CI, 2.14-2.64). Children's odds of having Medicaid or CHIP coverage increased when their parents were randomly selected to apply for Medicaid. Children whose parents were selected and subsequently obtained coverage benefited most. This study demonstrates a causal link between parents' access to Medicaid coverage and their children's coverage.

Sugar-sweetened beverages and weight gain in children and adults: a systematic review and meta-analysis123

PubMed Central

Pan, An; Willett, Walter C; Hu, Frank B

2013-01-01

Background: The relation between sugar-sweetened beverages (SSBs) and body weight remains controversial. Objective: We conducted a systematic review and meta-analysis to summarize the evidence in children and adults. Design: We searched PubMed, EMBASE, and Cochrane databases through March 2013 for prospective cohort studies and randomized controlled trials (RCTs) that evaluated the SSB-weight relation. Separate meta-analyses were conducted in children and adults and for cohorts and RCTs by using random- and fixed-effects models. Results: Thirty-two original articles were included in our meta-analyses: 20 in children (15 cohort studies, n = 25,745; 5 trials, n = 2772) and 12 in adults (7 cohort studies, n = 174,252; 5 trials, n = 292). In cohort studies, one daily serving increment of SSBs was associated with a 0.06 (95% CI: 0.02, 0.10) and 0.05 (95% CI: 0.03, 0.07)-unit increase in BMI in children and 0.22 kg (95% CI: 0.09, 0.34 kg) and 0.12 kg (95% CI: 0.10, 0.14 kg) weight gain in adults over 1 y in random- and fixed-effects models, respectively. RCTs in children showed reductions in BMI gain when SSBs were reduced [random and fixed effects: −0.17 (95% CI: −0.39, 0.05) and −0.12 (95% CI: −0.22, −0.2)], whereas RCTs in adults showed increases in body weight when SSBs were added (random and fixed effects: 0.85 kg; 95% CI: 0.50, 1.20 kg). Sensitivity analyses of RCTs in children showed more pronounced benefits in preventing weight gain in SSB substitution trials (compared with school-based educational programs) and among overweight children (compared with normal-weight children). Conclusion: Our systematic review and meta-analysis of prospective cohort studies and RCTs provides evidence that SSB consumption promotes weight gain in children and adults. PMID:23966427

Assessing different measures of population-level vaccine protection using a case-control study.

PubMed

Ali, Mohammad; You, Young Ae; Kanungo, Suman; Manna, Byomkesh; Deen, Jacqueline L; Lopez, Anna Lena; Wierzba, Thomas F; Bhattacharya, Sujit K; Sur, Dipika; Clemens, John D

2015-11-27

Case-control studies have not been examined for their utility in assessing population-level vaccine protection in individually randomized trials. We used the data of a randomized, placebo-controlled trial of a cholera vaccine to compare the results of case-control analyses with those of cohort analyses. Cases of cholera were selected from the trial population followed for three years following dosing. For each case, we selected 4 age-matched controls who had not developed cholera. For each case and control, GIS was used to calculate vaccine coverage of individuals in a surrounding "virtual" cluster. Specific selection strategies were used to evaluate the vaccine protective effects. 66,900 out of 108,389 individuals received two doses of the assigned regimen. For direct protection among subjects in low vaccine coverage clusters, we observed 78% (95% CI: 47-91%) protection in a cohort analysis and 84% (95% CI: 60-94%) in case-control analysis after adjusting for confounding factors. Using our GIS-based approach, estimated indirect protection was 52% (95% CI: 10-74%) in cohort and 76% (95% CI: 47-89%) in case control analysis. Estimates of total and overall effectiveness were similar for cohort and case-control analyses. The findings show that case-control analyses of individually randomized vaccine trials may be used to evaluate direct as well as population-level vaccine protection. Copyright © 2015. Published by Elsevier Ltd.

A Randomized Trial of an Elementary School Mathematics Software Intervention: Spatial-Temporal Math

ERIC Educational Resources Information Center

Rutherford, Teomara; Farkas, George; Duncan, Greg; Burchinal, Margaret; Kibrick, Melissa; Graham, Jeneen; Richland, Lindsey; Tran, Natalie; Schneider, Stephanie; Duran, Lauren; Martinez, Michael E.

2014-01-01

Fifty-two low performing schools were randomly assigned to receive Spatial-Temporal (ST) Math, a supplemental mathematics software and instructional program, in second/third or fourth/fifth grades or to a business-as-usual control. Analyses reveal a negligible effect of ST Math on mathematics scores, which did not differ significantly across…

Flux control coefficients determined by inhibitor titration: the design and analysis of experiments to minimize errors.

PubMed Central

Small, J R

1993-01-01

This paper is a study into the effects of experimental error on the estimated values of flux control coefficients obtained using specific inhibitors. Two possible techniques for analysing the experimental data are compared: a simple extrapolation method (the so-called graph method) and a non-linear function fitting method. For these techniques, the sources of systematic errors are identified and the effects of systematic and random errors are quantified, using both statistical analysis and numerical computation. It is shown that the graph method is very sensitive to random errors and, under all conditions studied, that the fitting method, even under conditions where the assumptions underlying the fitted function do not hold, outperformed the graph method. Possible ways of designing experiments to minimize the effects of experimental errors are analysed and discussed. PMID:8257434

Missing data in trial‐based cost‐effectiveness analysis: An incomplete journey

PubMed Central

Gomes, Manuel; Carpenter, James R.

2018-01-01

SUMMARY Cost‐effectiveness analyses (CEA) conducted alongside randomised trials provide key evidence for informing healthcare decision making, but missing data pose substantive challenges. Recently, there have been a number of developments in methods and guidelines addressing missing data in trials. However, it is unclear whether these developments have permeated CEA practice. This paper critically reviews the extent of and methods used to address missing data in recently published trial‐based CEA. Issues of the Health Technology Assessment journal from 2013 to 2015 were searched. Fifty‐two eligible studies were identified. Missing data were very common; the median proportion of trial participants with complete cost‐effectiveness data was 63% (interquartile range: 47%–81%). The most common approach for the primary analysis was to restrict analysis to those with complete data (43%), followed by multiple imputation (30%). Half of the studies conducted some sort of sensitivity analyses, but only 2 (4%) considered possible departures from the missing‐at‐random assumption. Further improvements are needed to address missing data in cost‐effectiveness analyses conducted alongside randomised trials. These should focus on limiting the extent of missing data, choosing an appropriate method for the primary analysis that is valid under contextually plausible assumptions, and conducting sensitivity analyses to departures from the missing‐at‐random assumption. PMID:29573044

Genetic parameters for growth characteristics of free-range chickens under univariate random regression models.

PubMed

Rovadoscki, Gregori A; Petrini, Juliana; Ramirez-Diaz, Johanna; Pertile, Simone F N; Pertille, Fábio; Salvian, Mayara; Iung, Laiza H S; Rodriguez, Mary Ana P; Zampar, Aline; Gaya, Leila G; Carvalho, Rachel S B; Coelho, Antonio A D; Savino, Vicente J M; Coutinho, Luiz L; Mourão, Gerson B

2016-09-01

Repeated measures from the same individual have been analyzed by using repeatability and finite dimension models under univariate or multivariate analyses. However, in the last decade, the use of random regression models for genetic studies with longitudinal data have become more common. Thus, the aim of this research was to estimate genetic parameters for body weight of four experimental chicken lines by using univariate random regression models. Body weight data from hatching to 84 days of age (n = 34,730) from four experimental free-range chicken lines (7P, Caipirão da ESALQ, Caipirinha da ESALQ and Carijó Barbado) were used. The analysis model included the fixed effects of contemporary group (gender and rearing system), fixed regression coefficients for age at measurement, and random regression coefficients for permanent environmental effects and additive genetic effects. Heterogeneous variances for residual effects were considered, and one residual variance was assigned for each of six subclasses of age at measurement. Random regression curves were modeled by using Legendre polynomials of the second and third orders, with the best model chosen based on the Akaike Information Criterion, Bayesian Information Criterion, and restricted maximum likelihood. Multivariate analyses under the same animal mixed model were also performed for the validation of the random regression models. The Legendre polynomials of second order were better for describing the growth curves of the lines studied. Moderate to high heritabilities (h(2) = 0.15 to 0.98) were estimated for body weight between one and 84 days of age, suggesting that selection for body weight at all ages can be used as a selection criteria. Genetic correlations among body weight records obtained through multivariate analyses ranged from 0.18 to 0.96, 0.12 to 0.89, 0.06 to 0.96, and 0.28 to 0.96 in 7P, Caipirão da ESALQ, Caipirinha da ESALQ, and Carijó Barbado chicken lines, respectively. Results indicate that genetic gain for body weight can be achieved by selection. Also, selection for body weight at 42 days of age can be maintained as a selection criterion. © 2016 Poultry Science Association Inc.

A reanalysis of cluster randomized trials showed interrupted time-series studies were valuable in health system evaluation.

PubMed

Fretheim, Atle; Zhang, Fang; Ross-Degnan, Dennis; Oxman, Andrew D; Cheyne, Helen; Foy, Robbie; Goodacre, Steve; Herrin, Jeph; Kerse, Ngaire; McKinlay, R James; Wright, Adam; Soumerai, Stephen B

2015-03-01

There is often substantial uncertainty about the impacts of health system and policy interventions. Despite that, randomized controlled trials (RCTs) are uncommon in this field, partly because experiments can be difficult to carry out. An alternative method for impact evaluation is the interrupted time-series (ITS) design. Little is known, however, about how results from the two methods compare. Our aim was to explore whether ITS studies yield results that differ from those of randomized trials. We conducted single-arm ITS analyses (segmented regression) based on data from the intervention arm of cluster randomized trials (C-RCTs), that is, discarding control arm data. Secondarily, we included the control group data in the analyses, by subtracting control group data points from intervention group data points, thereby constructing a time series representing the difference between the intervention and control groups. We compared the results from the single-arm and controlled ITS analyses with results based on conventional aggregated analyses of trial data. The findings were largely concordant, yielding effect estimates with overlapping 95% confidence intervals (CI) across different analytical methods. However, our analyses revealed the importance of a concurrent control group and of taking baseline and follow-up trends into account in the analysis of C-RCTs. The ITS design is valuable for evaluation of health systems interventions, both when RCTs are not feasible and in the analysis and interpretation of data from C-RCTs. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Modeling pattern in collections of parameters

USGS Publications Warehouse

Link, W.A.

1999-01-01

Wildlife management is increasingly guided by analyses of large and complex datasets. The description of such datasets often requires a large number of parameters, among which certain patterns might be discernible. For example, one may consider a long-term study producing estimates of annual survival rates; of interest is the question whether these rates have declined through time. Several statistical methods exist for examining pattern in collections of parameters. Here, I argue for the superiority of 'random effects models' in which parameters are regarded as random variables, with distributions governed by 'hyperparameters' describing the patterns of interest. Unfortunately, implementation of random effects models is sometimes difficult. Ultrastructural models, in which the postulated pattern is built into the parameter structure of the original data analysis, are approximations to random effects models. However, this approximation is not completely satisfactory: failure to account for natural variation among parameters can lead to overstatement of the evidence for pattern among parameters. I describe quasi-likelihood methods that can be used to improve the approximation of random effects models by ultrastructural models.

Metacognitive therapy versus cognitive behavioural therapy for depression: a randomized pilot study.

PubMed

Jordan, Jennifer; Carter, Janet D; McIntosh, Virginia V W; Fernando, Kumari; Frampton, Christopher M A; Porter, Richard J; Mulder, Roger T; Lacey, Cameron; Joyce, Peter R

2014-10-01

Metacognitive therapy (MCT) is one of the newer developments within cognitive therapy. This randomized controlled pilot study compared independently applied MCT with cognitive behavioural therapy (CBT) in outpatients with depression to explore the relative speed and efficacy of MCT, ahead of a planned randomized controlled trial. A total of 48 participants referred for outpatient therapy were randomized to up to 12 weeks of MCT or CBT. Key outcomes were reduction in depressive symptoms at week 4 and week 12, measured using the independent-clinician-rated Quick Inventory of Depressive Symptomatology16. Intention-to-treat and completer analyses as well as additional methods of reporting outcome of depression are presented. Both therapies were effective in producing clinically significant change in depressive symptoms, with moderate-to-large effect sizes obtained. No differences were detected between therapies in overall outcome or early change on clinician-rated or self-reported measures. Post-hoc analyses suggest that MCT may have been adversely affected by greater comorbidity. In this large pilot study conducted independently of MCT's developers, MCT was an effective treatment for outpatients with depression, with similar results overall to CBT. Insufficient power and imbalanced comorbidity limit conclusions regarding comparative efficacy so further studies of MCT and CBT are required. © The Royal Australian and New Zealand College of Psychiatrists 2014.

Conflicting results between randomized trials and observational studies on the impact of proton pump inhibitors on cardiovascular events when coadministered with dual antiplatelet therapy: systematic review.

PubMed

Melloni, Chiara; Washam, Jeffrey B; Jones, W Schuyler; Halim, Sharif A; Hasselblad, Victor; Mayer, Stephanie B; Heidenfelder, Brooke L; Dolor, Rowena J

2015-01-01

Discordant results have been reported on the effects of concomitant use of proton pump inhibitors (PPIs) and dual antiplatelet therapy (DAPT) for cardiovascular outcomes. We conducted a systematic review comparing the effectiveness and safety of concomitant use of PPIs and DAPT in the postdischarge treatment of unstable angina/non-ST-segment-elevation myocardial infarction patients. We searched for clinical studies in MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews, from 1995 to 2012. Reviewers screened and extracted data, assessed applicability and quality, and graded the strength of evidence. We performed meta-analyses of direct comparisons when outcomes and follow-up periods were comparable. Thirty-five studies were eligible. Five (4 randomized controlled trials and 1 observational) assessed the effect of omeprazole when added to DAPT; the other 30 (observational) assessed the effect of PPIs as a class when compared with no PPIs. Random-effects meta-analyses of the studies assessing PPIs as a class consistently reported higher event rates in patients receiving PPIs for various clinical outcomes at 1 year (composite ischemic end points, all-cause mortality, nonfatal MI, stroke, revascularization, and stent thrombosis). However, the results from randomized controlled trials evaluating omeprazole compared with placebo showed no difference in ischemic outcomes, despite a reduction in upper gastrointestinal bleeding with omeprazole. Large, well-conducted observational studies of PPIs and randomized controlled trials of omeprazole seem to provide conflicting results for the effect of PPIs on cardiovascular outcomes when coadministered with DAPT. Prospective trials that directly compare pharmacodynamic parameters and clinical events among specific PPI agents in patients with unstable angina/non-ST-segment-elevation myocardial infarction treated with DAPT are warranted. © 2015 American Heart Association, Inc.

Sensitivity subgroup analysis based on single-center vs. multi-center trial status when interpreting meta-analyses pooled estimates: the logical way forward.

PubMed

Alexander, Paul E; Bonner, Ashley J; Agarwal, Arnav; Li, Shelly-Anne; Hariharan, Abishek; Izhar, Zain; Bhatnagar, Neera; Alba, Carolina; Akl, Elie A; Fei, Yutong; Guyatt, Gordon H; Beyene, Joseph

2016-06-01

Prior studies regarding whether single-center trial estimates are larger than multi-center are equivocal. We examined the extent to which single-center trials yield systematically larger effects than multi-center trials. We searched the 119 core clinical journals and the Cochrane Database of Systematic Reviews for meta-analyses (MAs) of randomized controlled trials (RCTs) published during 2012. In this meta-epidemiologic study, for binary variables, we computed the pooled ratio of ORs (RORs), and for continuous outcomes mean difference in standardized mean differences (SMDs), we conducted weighted random-effects meta-regression and random-effects MA modeling. Our primary analyses were restricted to MAs that included at least five RCTs and in which at least 25% of the studies used each of single trial center (SC) and more trial center (MC) designs. We identified 81 MAs for the odds ratio (OR) and 43 for the SMD outcome measures. Based on our analytic plan, our primary analysis (core) is based on 25 MAs/241 RCTs (binary outcome) and 18 MAs/173 RCTs (continuous outcome). Based on the core analysis, we found no difference in magnitude of effect between SC and MC for binary outcomes [RORs: 1.02; 95% confidence interval (CI): 0.83, 1.24; I(2) 20.2%]. Effect sizes were systematically larger for SC than MC for the continuous outcome measure (mean difference in SMDs: -0.13; 95% CI: -0.21, -0.05; I(2) 0%). Our results do not support prior findings of larger effects in SC than MC trials addressing binary outcomes but show a very similar small increase in effect in SC than MC trials addressing continuous outcomes. Authors of systematic reviews would be wise to include all trials irrespective of SC vs. MC design and address SC vs. MC status as a possible explanation of heterogeneity (and consider sensitivity analyses). Copyright © 2015 Elsevier Inc. All rights reserved.

Random Effects: Variance Is the Spice of Life.

PubMed

Jupiter, Daniel C

Covariates in regression analyses allow us to understand how independent variables of interest impact our dependent outcome variable. Often, we consider fixed effects covariates (e.g., gender or diabetes status) for which we examine subjects at each value of the covariate. We examine both men and women and, within each gender, examine both diabetic and nondiabetic patients. Occasionally, however, we consider random effects covariates for which we do not examine subjects at every value. For example, we examine patients from only a sample of hospitals and, within each hospital, examine both diabetic and nondiabetic patients. The random sampling of hospitals is in contrast to the complete coverage of all genders. In this column I explore the differences in meaning and analysis when thinking about fixed and random effects variables. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

The Transfer of Cognitive Speed of Processing Training to Older Adults' Driving Mobility Across 5 Years.

PubMed

Ross, Lesley A; Edwards, Jerri D; O'Connor, Melissa L; Ball, Karlene K; Wadley, Virginia G; Vance, David E

2016-01-01

Multilevel models assessed the effects of cognitive speed of processing training (SPT) on older adults' self-reported driving using intention-to-treat (ITT, randomization to training or control conditions) and dosage (treatment-received via number of training sessions) analyses across 5 years. Participants randomized to SPT (n = 598) were compared with those randomized to either the no-contact control (n = 598) or memory training, which served as an active control (n = 610). Driving mobility (frequency, exposure, and space) was assessed over time. No significant effects were found within the ITT analyses. However, number of SPT sessions did affect driving mobility outcomes. In the full sample (N = 1,806), higher SPT doses were associated with maintained driving frequency as compared with both control groups, but no effects were found for driving exposure or space. Subsample analyses (n = 315) revealed that persons at-risk for mobility declines (i.e., poor initial processing speed) who received additional booster SPT sessions reported greater maintenance of both driving frequency and exposure over time as compared with the no-contact and active control groups. These results and prior research indicate that cognitive SPT transfers to prolonged driving mobility among older adults. Future research should investigate the mechanisms behind transfer effects to real-world activities, such as driving. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Random regression analyses using B-spline functions to model growth of Nellore cattle.

PubMed

Boligon, A A; Mercadante, M E Z; Lôbo, R B; Baldi, F; Albuquerque, L G

2012-02-01

The objective of this study was to estimate (co)variance components using random regression on B-spline functions to weight records obtained from birth to adulthood. A total of 82 064 weight records of 8145 females obtained from the data bank of the Nellore Breeding Program (PMGRN/Nellore Brazil) which started in 1987, were used. The models included direct additive and maternal genetic effects and animal and maternal permanent environmental effects as random. Contemporary group and dam age at calving (linear and quadratic effect) were included as fixed effects, and orthogonal Legendre polynomials of age (cubic regression) were considered as random covariate. The random effects were modeled using B-spline functions considering linear, quadratic and cubic polynomials for each individual segment. Residual variances were grouped in five age classes. Direct additive genetic and animal permanent environmental effects were modeled using up to seven knots (six segments). A single segment with two knots at the end points of the curve was used for the estimation of maternal genetic and maternal permanent environmental effects. A total of 15 models were studied, with the number of parameters ranging from 17 to 81. The models that used B-splines were compared with multi-trait analyses with nine weight traits and to a random regression model that used orthogonal Legendre polynomials. A model fitting quadratic B-splines, with four knots or three segments for direct additive genetic effect and animal permanent environmental effect and two knots for maternal additive genetic effect and maternal permanent environmental effect, was the most appropriate and parsimonious model to describe the covariance structure of the data. Selection for higher weight, such as at young ages, should be performed taking into account an increase in mature cow weight. Particularly, this is important in most of Nellore beef cattle production systems, where the cow herd is maintained on range conditions. There is limited modification of the growth curve of Nellore cattle with respect to the aim of selecting them for rapid growth at young ages while maintaining constant adult weight.

Peritoneal Dialysate Glucose Load and Systemic Glucose Metabolism in Non-Diabetics: Results from the GLOBAL Fluid Cohort Study

PubMed Central

Chess, James; Do, Jun-Young; Noh, Hyunjin; Lee, Hi-Bahl; Kim, Yong-Lim; Summers, Angela; Williams, Paul Ford; Davison, Sara; Dorval, Marc

2016-01-01

Background and Objectives Glucose control is a significant predictor of mortality in diabetic peritoneal dialysis (PD) patients. During PD, the local toxic effects of intra-peritoneal glucose are well recognized, but despite large amounts of glucose being absorbed, the systemic effects of this in non-diabetic patients are not clear. We sought to clarify whether dialysate glucose has an effect upon systemic glucose metabolism. Methods and Materials We analysed the Global Fluid Study cohort, a prospective, observational cohort study initiated in 2002. A subset of 10 centres from 3 countries with high data quality were selected (368 incident and 272 prevalent non-diabetic patients), with multilevel, multivariable analysis of the reciprocal of random glucose levels, and a stratified-by-centre Cox survival analysis. Results The median follow up was 5.6 and 6.4 years respectively in incident and prevalent patients. On multivariate analysis, serum glucose increased with age (β = -0.007, 95%CI -0.010, -0.004) and decreased with higher serum sodium (β = 0.002, 95%CI 0.0005, 0.003) in incident patients and increased with dialysate glucose (β = -0.0002, 95%CI -0.0004, -0.00006) in prevalent patients. Levels suggested undiagnosed diabetes in 5.4% of prevalent patients. Glucose levels predicted death in unadjusted analyses of both incident and prevalent groups but in an adjusted survival analysis they did not (for random glucose 6–10 compared with <6, Incident group HR 0.92, 95%CI 0.58, 1.46, Prevalent group HR 1.42, 95%CI 0.86, 2.34). Conclusions In prevalent non-diabetic patients, random glucose levels at a diabetic level are under-recognised and increase with dialysate glucose load. Random glucose levels predict mortality in unadjusted analyses, but this association has not been proven in adjusted analyses. PMID:27249020

Examination of Individual Differences in Outcomes from a Randomized Controlled Clinical Trial Comparing Formal and Informal Individual Auditory Training Programs

ERIC Educational Resources Information Center

Smith, Sherri L.; Saunders, Gabrielle H.; Chisolm, Theresa H.; Frederick, Melissa; Bailey, Beth A.

2016-01-01

Purpose: The purpose of this study was to determine if patient characteristics or clinical variables could predict who benefits from individual auditory training. Method: A retrospective series of analyses were performed using a data set from a large, multisite, randomized controlled clinical trial that compared the treatment effects of at-home…

Practical Effects of Classwide Mathematics Intervention

ERIC Educational Resources Information Center

VanDerHeyden, Amanda M.; Codding, Robin S.

2015-01-01

The current article presents additional analyses of a classwide mathematics intervention, from a previously reported randomized controlled trial, to offer new information about the treatment and to demonstrate the utility of different types of effect sizes. Multilevel modeling was used to examine treatment effects by race, sex, socioeconomic…

Modeling stimulus variation in three common implicit attitude tasks.

PubMed

Wolsiefer, Katie; Westfall, Jacob; Judd, Charles M

2017-08-01

We explored the consequences of ignoring the sampling variation due to stimuli in the domain of implicit attitudes. A large literature in psycholinguistics has examined the statistical treatment of random stimulus materials, but the recommendations from this literature have not been applied to the social psychological literature on implicit attitudes. This is partly because of inherent complications in applying crossed random-effect models to some of the most common implicit attitude tasks, and partly because no work to date has demonstrated that random stimulus variation is in fact consequential in implicit attitude measurement. We addressed this problem by laying out statistically appropriate and practically feasible crossed random-effect models for three of the most commonly used implicit attitude measures-the Implicit Association Test, affect misattribution procedure, and evaluative priming task-and then applying these models to large datasets (average N = 3,206) that assess participants' implicit attitudes toward race, politics, and self-esteem. We showed that the test statistics from the traditional analyses are substantially (about 60 %) inflated relative to the more-appropriate analyses that incorporate stimulus variation. Because all three tasks used the same stimulus words and faces, we could also meaningfully compare the relative contributions of stimulus variation across the tasks. In an appendix, we give syntax in R, SAS, and SPSS for fitting the recommended crossed random-effects models to data from all three tasks, as well as instructions on how to structure the data file.

Effects of atypical antipsychotic drugs on QT interval in patients with mental disorders

PubMed Central

Aronow, Wilbert S.

2018-01-01

Background Drug-induced QT prolongation is associated with higher risk of cardiac arrhythmias and cardiovascular mortality. We investigated the effects of atypical antipsychotic drugs on QT interval in children and adults with mental disorders. Methods We conducted random-effects direct frequentist meta-analyses of aggregate data from randomized controlled trials (RCT) and appraised the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Our search in PubMed, EMBASE, the Cochrane Library, clinicaltrials.gov, and PharmaPendium up to October 2017 identified studies that examined aripiprazole, quetiapine, risperidone, olanzapine, ziprasidone and brexpiprazole. Results Low quality evidence suggests that aripiprazole (four meta-analyses and twelve RCTs), brexpiprazole (one systematic review and four RCTs) or olanzapine (five meta-analyses and twenty RCTs) do not increase QT interval. Low quality evidence suggests that ziprasidone (five meta-analyses and 11 RCTs) increases QT interval and the rates of QT prolongation while risperidone (four meta-analyses, 70 RCTs) and quetiapine (two meta-analyses and seven RCTs) are associated with QT prolongation and greater odds of torsades de pointes ventricular tachycardia especially in cases of drug overdose. Conclusions The main conclusion of our study is that in people with mental disorders and under treatment with atypical antipsychotic drugs, in order to avoid QT prolongation and reduce the risk of ventricular tachycardia clinicians may recommend aripiprazole, brexpiprazole or olanzapine in licensed doses. Long-term comparative safety needs to be established. PMID:29862236

The hemodynamic effects of intravenous paracetamol (acetaminophen) vs normal saline in cardiac surgery patients: A single center placebo controlled randomized study

PubMed Central

Churilov, Leonid

2018-01-01

The hemodynamic effects of intravenous (IV) paracetamol in patients undergoing cardiac surgery are unknown. We performed a prospective single center placebo controlled randomized study with parallel group design in adult patients undergoing elective cardiac surgery. Participants received paracetamol (1 gram) IV or placebo (an equal volume of 0.9% saline) preoperatively followed by two postoperative doses 6 hours apart. The primary endpoint was the absolute change in systolic (SBP) 30 minutes after the preoperative infusion, analysed using an ANCOVA model. Secondary endpoints included absolute changes in mean arterial pressure (MAP) and diastolic blood pressure (DPB), and other key hemodynamic variables after each infusion. All other endpoints were analysed using random-effect generalized least squares regression modelling with individual patients treated as random effects. Fifty participants were randomly assigned to receive paracetamol (n = 25) or placebo (n = 25). Post preoperative infusion, paracetamol decreased SBP by a mean (SD) of 13 (18) mmHg, p = 0.02, compared to a mean (SD) of 1 (11) mmHg with saline. Paracetamol decreased MAP and DBP by a mean (SD) of 9 (12) mmHg and 8 (9) mmHg (p = 0.01 and 0.02), respectively, compared to a mean (SD) of 1 (8) mmHg and 0 (6) mmHg with placebo. Postoperatively, there were no significant differences in pressure or flow based hemodynamic parameters in both groups. This study provides high quality evidence that the administration of IV paracetamol in patients undergoing cardiac surgery causes a transient decrease in preoperative blood pressure when administered before surgery but no adverse hemodynamic effects when administered in the postoperative setting. PMID:29659631

The hemodynamic effects of intravenous paracetamol (acetaminophen) vs normal saline in cardiac surgery patients: A single center placebo controlled randomized study.

PubMed

Chiam, Elizabeth; Bellomo, Rinaldo; Churilov, Leonid; Weinberg, Laurence

2018-01-01

The hemodynamic effects of intravenous (IV) paracetamol in patients undergoing cardiac surgery are unknown. We performed a prospective single center placebo controlled randomized study with parallel group design in adult patients undergoing elective cardiac surgery. Participants received paracetamol (1 gram) IV or placebo (an equal volume of 0.9% saline) preoperatively followed by two postoperative doses 6 hours apart. The primary endpoint was the absolute change in systolic (SBP) 30 minutes after the preoperative infusion, analysed using an ANCOVA model. Secondary endpoints included absolute changes in mean arterial pressure (MAP) and diastolic blood pressure (DPB), and other key hemodynamic variables after each infusion. All other endpoints were analysed using random-effect generalized least squares regression modelling with individual patients treated as random effects. Fifty participants were randomly assigned to receive paracetamol (n = 25) or placebo (n = 25). Post preoperative infusion, paracetamol decreased SBP by a mean (SD) of 13 (18) mmHg, p = 0.02, compared to a mean (SD) of 1 (11) mmHg with saline. Paracetamol decreased MAP and DBP by a mean (SD) of 9 (12) mmHg and 8 (9) mmHg (p = 0.01 and 0.02), respectively, compared to a mean (SD) of 1 (8) mmHg and 0 (6) mmHg with placebo. Postoperatively, there were no significant differences in pressure or flow based hemodynamic parameters in both groups. This study provides high quality evidence that the administration of IV paracetamol in patients undergoing cardiac surgery causes a transient decrease in preoperative blood pressure when administered before surgery but no adverse hemodynamic effects when administered in the postoperative setting.

A Randomized Clinical Trial of Cognitive Enhancement Therapy for Adults with Autism Spectrum Disorders

DTIC Science & Technology

2015-10-01

This project is focused on conducting the first randomized-controlled trial of Cognitive Enhancement Therapy (CET) in 54 verbal adults with autism ...of the neuroplastic effects of CET on brain function in support of cognitive enhancement in adult autism . Analyses of treatment effects to date...the need and potential for CET to be a significant treatment advance for verbal adults with autism . Importantly, improvements were found in daily life function and in brain circuitry supporting core abilities.

The response of an airplane to random atmospheric disturbances

NASA Technical Reports Server (NTRS)

Diederich, Franklin W

1957-01-01

The statistical approach to the gust-load problem which consists in considering flight through turbulent air to be a stationary random process is extended by including the effect of lateral variation of the instantaneous gust intensity on the aerodynamic forces. The forces obtained in this manner are used in dynamic analyses of rigid and flexible airplanes free to move vertically, in pitch, and in roll. The effect of the interaction of longitudinal, vertical, and lateral gusts on the wing stresses is also considered.

A Randomized Controlled Trial of Two Syntactic Treatment Procedures With Cantonese-Speaking, School-Age Children With Language Disorders.

PubMed

To, Carol K S; Lui, Hoi Ming; Li, Xin Xin; Lam, Gary Y H

2015-08-01

In this study, we aimed to evaluate the efficacy of sentence-combining (SC) and narrative-based (NAR) intervention approaches to syntax intervention using a randomized-controlled-trial design. Fifty-two Cantonese-speaking, school-age children with language impairment were assigned randomly to either the SC or the NAR treatment arm. Seven children did not receive treatment as assigned. Intervention in both arms targeted the same complex syntactical structures. The SC group focused on sentence combination training, whereas the NAR group made use of narratives in which the target structures were embedded. Pretest and posttest performances measured using a standardized language assessment were subjected to analyses of covariance mixed-effect-model analyses of variance. Children in both treatment arms demonstrated significant growth after 4 months of intervention. The main effect between treatment arms and time was not significant after controlling the pretest performance, suggesting that both treatment approaches showed similar effects. The main effect of time was significant. This study provided evidence to support language intervention in the school years in Cantonese-speaking children. However, neither approach was shown to be more efficacious than the other. Future researchers could examine the effects of a longer treatment period and include functional outcome measures.

Meta-analyses on intra-aortic balloon pump in cardiogenic shock complicating acute myocardial infarction may provide biased results.

PubMed

Acconcia, M C; Caretta, Q; Romeo, F; Borzi, M; Perrone, M A; Sergi, D; Chiarotti, F; Calabrese, C M; Sili Scavalli, A; Gaudio, C

2018-04-01

Intra-aortic balloon pump (IABP) is the device most commonly investigated in patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI). Recently meta-analyses on this topic showed opposite results: some complied with the actual guideline recommendations, while others did not, due to the presence of bias. We investigated the reasons for the discrepancy among meta-analyses and strategies employed to avoid the potential source of bias. Scientific databases were searched for meta-analyses of IABP support in AMI complicated by CS. The presence of clinical diversity, methodological diversity and statistical heterogeneity were analyzed. When we found clinical or methodological diversity, we reanalyzed the data by comparing the patients selected for homogeneous groups. When the fixed effect model was employed despite the presence of statistical heterogeneity, the meta-analysis was repeated adopting the random effect model, with the same estimator used in the original meta-analysis. Twelve meta-analysis were selected. Six meta-analyses of randomized controlled trials (RCTs) were inconclusive because underpowered to detect the IABP effect. Five included RCTs and observational studies (Obs) and one only Obs. Some meta-analyses on RCTs and Obs had biased results due to presence of clinical and/or methodological diversity. The reanalysis of data reallocated for homogeneous groups was no more in contrast with guidelines recommendations. Meta-analyses performed without controlling for clinical and/or methodological diversity, represent a confounding message against a good clinical practice. The reanalysis of data demonstrates the validity of the current guidelines recommendations in addressing clinical decision making in providing IABP support in AMI complicated by CS.

Understanding Frame-of-Reference Training Success: A Social Learning Theory Perspective

ERIC Educational Resources Information Center

Sulsky, Lorne M.; Kline, Theresa J. B.

2007-01-01

Employing the social learning theory (SLT) perspective on training, we analysed the effects of alternative frame-of-reference (FOR) training protocols on various criteria of training effectiveness. Undergraduate participants (N = 65) were randomly assigned to one of four FOR training conditions and a control condition. Training effectiveness was…

PROSPERA: a randomized, controlled trial evaluating rasagiline in progressive supranuclear palsy.

PubMed

Nuebling, Georg; Hensler, Mira; Paul, Sabine; Zwergal, Andreas; Crispin, Alexander; Lorenzl, Stefan

2016-08-01

To date, pharmacological treatment options for progressive supranuclear palsy (PSP), a neurodegenerative tauopathy, are limited. The MAO-B inhibitor rasagiline has shown neuroprotective effects in preclinical models of neurodegeneration. To evaluate the safety, tolerability and therapeutic effect of rasagiline on symptom progression in PSP. In this 1-year randomized, double-blind, placebo-controlled trial, 44 patients fulfilling the NINDS-PSP criteria were randomized to 1 mg/d rasagiline or placebo. The combined primary endpoint included symptom progression as measured by the PSP rating scale (PSP-RS) and the requirement of L-dopa rescue medication. Secondary endpoints included Schwab and England Activities of Daily Living (SEADL), Montgomery-Åsberg Depression Rating Scale, Mini Mental State Examination, Frontal Assessment Battery and posturographic measurements. Of the 44 patients randomized, 26 completed the trial per protocol. Rasagiline was well tolerated, with a slight increase of known side effects (hallucinations, ventricular extrasystoles). No effect on the primary endpoint (p = 0.496) was detected. Symptom progression averaged at 11.2 (rasagiline) and 10.8 (placebo) points per year (ΔPSP-RS). No difference was seen in SEADL, depression, cognitive function, frontal executive function and posturographic measurements. Post hoc analyses of PSP-RS subdomains indicate a potential beneficial effect in the "limb motor" subdomain, whereas performance appeared lower in the "mentation" and "history" subdomains in the treatment group. While rasagiline is well tolerated in PSP, a beneficial effect on overall symptom progression was not detected. Post hoc analyses suggest the implementation of more specific endpoints in future studies.

Effect of Expanding Medicaid for Parents on Children’s Health Insurance Coverage

PubMed Central

DeVoe, Jennifer E.; Marino, Miguel; Angier, Heather; O’Malley, Jean P.; Crawford, Courtney; Nelson, Christine; Tillotson, Carrie J.; Bailey, Steffani R.; Gallia, Charles; Gold, Rachel

2016-01-01

IMPORTANCE In the United States, health insurance is not universal. Observational studies show an association between uninsured parents and children. This association persisted even after expansions in child-only public health insurance. Oregon’s randomized Medicaid expansion for adults, known as the Oregon Experiment, created a rare opportunity to assess causality between parent and child coverage. OBJECTIVE To estimate the effect on a child’s health insurance coverage status when (1) a parent randomly gains access to health insurance and (2) a parent obtains coverage. DESIGN, SETTING, AND PARTICIPANTS Oregon Experiment randomized natural experiment assessing the results of Oregon’s 2008 Medicaid expansion. We used generalized estimating equation models to examine the longitudinal effect of a parent randomly selected to apply for Medicaid on their child’s Medicaid or Children’s Health Insurance Program (CHIP) coverage (intent-to-treat analyses). We used per-protocol analyses to understand the impact on children’s coverage when a parent was randomly selected to apply for and obtained Medicaid. Participants included 14 409 children aged 2 to 18 years whose parents participated in the Oregon Experiment. EXPOSURES For intent-to-treat analyses, the date a parent was selected to apply for Medicaid was considered the date the child was exposed to the intervention. In per-protocol analyses, exposure was defined as whether a selected parent obtained Medicaid. MAIN OUTCOMES AND MEASURES Children’s Medicaid or CHIP coverage, assessed monthly and in 6-month intervals relative to their parent’s selection date. RESULTS In the immediate period after selection, children whose parents were selected to apply significantly increased from 3830 (61.4%) to 4152 (66.6%) compared with a nonsignificant change from 5049 (61.8%) to 5044 (61.7%) for children whose parents were not selected to apply. Children whose parents were randomly selected to apply for Medicaid had 18% higher odds of being covered in the first 6 months after parent’s selection compared with children whose parents were not selected (adjusted odds ratio [AOR] = 1.18; 95% CI, 1.10–1.27). The effect remained significant during months 7 to 12 (AOR = 1.11; 95% CI, 1.03–1.19); months 13 to 18 showed a positive but not significant effect (AOR = 1.07; 95% CI, 0.99–1.14). Children whose parents were selected and obtained coverage had more than double the odds of having coverage compared with children whose parents were not selected and did not gain coverage (AOR = 2.37; 95% CI, 2.14–2.64). CONCLUSIONS AND RELEVANCE Children’s odds of having Medicaid or CHIP coverage increased when their parents were randomly selected to apply for Medicaid. Children whose parents were selected and subsequently obtained coverage benefited most. This study demonstrates a causal link between parents’ access to Medicaid coverage and their children’s coverage. PMID:25561041

Effectiveness of a novel integrative online treatment for depression (Deprexis): randomized controlled trial.

PubMed

Meyer, Björn; Berger, Thomas; Caspar, Franz; Beevers, Christopher G; Andersson, Gerhard; Weiss, Mario

2009-05-11

Depression is associated with immense suffering and costs, and many patients receive inadequate care, often because of the limited availability of treatment. Web-based treatments may play an increasingly important role in closing this gap between demand and supply. We developed the integrative, Web-based program Deprexis, which covers therapeutic approaches such as behavioral activation, cognitive restructuring, mindfulness/acceptance exercises, and social skills training. To evaluate the effectiveness of the Web-based intervention in a randomized controlled trial. There were 396 adults recruited via Internet depression forums in Germany, and they were randomly assigned in an 80:20 weighted randomization sequence to either 9 weeks of immediate-program-access as an add-on to treatment-as-usual (N = 320), or to a 9-week delayed-access plus treatment-as-usual condition (N = 76). At pre- and post-treatment and 6-month follow-up, we measured depression (Beck Depression Inventory) as the primary outcome measure and social functioning (Work and Social Adjustment Scale) as the secondary outcome measure. Complete analyses and intention-to-treat analyses were performed. Of 396 participants, 216 (55%) completed the post-measurement 9 weeks later. Available case analyses revealed a significant reduction in depression severity (BDI), Cohen's d = .64 (CI 95% = 0.33 - 0.94), and significant improvement in social functioning (WSA), Cohen's d = .64, 95% (CI 95% = 0.33 - 0.95). These improvements were maintained at 6-month follow-up. Intention-to-treat analyses confirmed significant effects on depression and social functioning improvements (BDI: Cohen's d = .30, CI 95% = 0.05 - 0.55; WSA: Cohen's d = .36, CI 95% = 0.10 - 0.61). Moreover, a much higher percentage of patients in the intervention group experienced a significant reduction of depression symptoms (BDI: odds ratio [OR] = 6.8, CI 95% = 2.90 - 18.19) and recovered more often (OR = 17.3, 95% CI 2.3 - 130). More than 80% of the users felt subjectively that the program had been helpful. This integrative, Web-based intervention was effective in reducing symptoms of depression and in improving social functioning. Findings suggest that the program could serve as an adjunctive or stand-alone treatment tool for patients suffering from symptoms of depression.

Revisiting sample size: are big trials the answer?

PubMed

Lurati Buse, Giovanna A L; Botto, Fernando; Devereaux, P J

2012-07-18

The superiority of the evidence generated in randomized controlled trials over observational data is not only conditional to randomization. Randomized controlled trials require proper design and implementation to provide a reliable effect estimate. Adequate random sequence generation, allocation implementation, analyses based on the intention-to-treat principle, and sufficient power are crucial to the quality of a randomized controlled trial. Power, or the probability of the trial to detect a difference when a real difference between treatments exists, strongly depends on sample size. The quality of orthopaedic randomized controlled trials is frequently threatened by a limited sample size. This paper reviews basic concepts and pitfalls in sample-size estimation and focuses on the importance of large trials in the generation of valid evidence.

The Efficacy of Mindfulness-Based Interventions in Primary Care: A Meta-Analytic Review.

PubMed

Demarzo, Marcelo M P; Montero-Marin, Jesús; Cuijpers, Pim; Zabaleta-del-Olmo, Edurne; Mahtani, Kamal R; Vellinga, Akke; Vicens, Caterina; López-del-Hoyo, Yolanda; García-Campayo, Javier

2015-11-01

Positive effects have been reported after mindfulness-based interventions (MBIs) in diverse clinical and nonclinical populations. Primary care is a key health care setting for addressing common chronic conditions, and an effective MBI designed for this setting could benefit countless people worldwide. Meta-analyses of MBIs have become popular, but little is known about their efficacy in primary care. Our aim was to investigate the application and efficacy of MBIs that address primary care patients. We performed a meta-analytic review of randomized controlled trials addressing the effect of MBIs in adult patients recruited from primary care settings. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane guidelines were followed. Effect sizes were calculated with the Hedges g in random effects models. The meta-analyses were based on 6 trials having a total of 553 patients. The overall effect size of MBI compared with a control condition for improving general health was moderate (g = 0.48; P = .002), with moderate heterogeneity (I(2) = 59; P <.05). We found no indication of publication bias in the overall estimates. MBIs were efficacious for improving mental health (g = 0.56; P = .007), with a high heterogeneity (I(2) = 78; P <.01), and for improving quality of life (g = 0.29; P = .002), with a low heterogeneity (I(2) = 0; P >.05). Although the number of randomized controlled trials applying MBIs in primary care is still limited, our results suggest that these interventions are promising for the mental health and quality of life of primary care patients. We discuss innovative approaches for implementing MBIs, such as complex intervention and stepped care. © 2015 Annals of Family Medicine, Inc.

A Meta-Analysis of Cognitive Behavior Therapy and Medication for Child Obsessive Compulsive Disorder: Moderators of Treatment Efficacy, Response, and Remission

PubMed Central

McGuire, Joseph F.; Piacentini, John; Lewin, Adam B.; Brennan, Erin A; Murphy, Tanya K.; Storch, Eric A.

2015-01-01

Background Individual randomized controlled trials (RCTs) have demonstrated the efficacy of cognitive behavioral therapy (CBT) and serotonin reuptake inhibitors (SRIs) for the treatment of youth with obsessive-compulsive disorder (OCD). While meta-analyses have confirmed these results, there has been minimal examination of treatment moderators or an examination of treatment response and symptom/diagnostic remission for these two treatment types. The present report examined the treatment efficacy, treatment response, and symptom/diagnostic remission for youth with OCD receiving either CBT or SRIs relative to comparison conditions, and examined treatment moderators. Method A comprehensive literature search identified 20 RCTs that met inclusion criteria, and produced a sample size of 507 CBT participants and 789 SRI participants. Results Random effects meta-analyses of CBT trials found large treatment effects for treatment efficacy (g=1.21), treatment response [relative risk (RR)=3.93], and symptom/diagnostic remission (RR=5.40). Greater co-occurring anxiety disorders, therapeutic contact, and lower treatment attrition were associated with greater CBT effects. The number needed to treat (NNT) was three for treatment response and symptom/diagnostic remission. Random effects meta-analyses of SRI trials found a moderate treatment effect for treatment efficacy (g=0.50), treatment response (RR=1.80), and symptom/diagnostic remission (RR=2.06). Greater methodological quality was associated with a lower treatment response for SRI trials. The NNT was five for treatment response and symptom/diagnostic remission. Conclusions Findings demonstrate the treatment effects for CBT and SRIs across three important outcome metrics, and provide evidence for moderators of CBT across trials. PMID:26130211

The Efficacy of Mindfulness-Based Interventions in Primary Care: A Meta-Analytic Review

PubMed Central

Demarzo, Marcelo M.P.; Montero-Marin, Jesús; Cuijpers, Pim; Zabaleta-del-Olmo, Edurne; Mahtani, Kamal R.; Vellinga, Akke; Vicens, Caterina; López-del-Hoyo, Yolanda; García-Campayo, Javier

2015-01-01

PURPOSE Positive effects have been reported after mindfulness-based interventions (MBIs) in diverse clinical and nonclinical populations. Primary care is a key health care setting for addressing common chronic conditions, and an effective MBI designed for this setting could benefit countless people worldwide. Meta-analyses of MBIs have become popular, but little is known about their efficacy in primary care. Our aim was to investigate the application and efficacy of MBIs that address primary care patients. METHODS We performed a meta-analytic review of randomized controlled trials addressing the effect of MBIs in adult patients recruited from primary care settings. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane guidelines were followed. Effect sizes were calculated with the Hedges g in random effects models. RESULTS The meta-analyses were based on 6 trials having a total of 553 patients. The overall effect size of MBI compared with a control condition for improving general health was moderate (g = 0.48; P = .002), with moderate heterogeneity (I2 = 59; P <.05). We found no indication of publication bias in the overall estimates. MBIs were efficacious for improving mental health (g = 0.56; P = .007), with a high heterogeneity (I2 = 78; P <.01), and for improving quality of life (g = 0.29; P = .002), with a low heterogeneity (I2 = 0; P >.05). CONCLUSIONS Although the number of randomized controlled trials applying MBIs in primary care is still limited, our results suggest that these interventions are promising for the mental health and quality of life of primary care patients. We discuss innovative approaches for implementing MBIs, such as complex intervention and stepped care. PMID:26553897

Missing data in trial-based cost-effectiveness analysis: An incomplete journey.

PubMed

Leurent, Baptiste; Gomes, Manuel; Carpenter, James R

2018-06-01

Cost-effectiveness analyses (CEA) conducted alongside randomised trials provide key evidence for informing healthcare decision making, but missing data pose substantive challenges. Recently, there have been a number of developments in methods and guidelines addressing missing data in trials. However, it is unclear whether these developments have permeated CEA practice. This paper critically reviews the extent of and methods used to address missing data in recently published trial-based CEA. Issues of the Health Technology Assessment journal from 2013 to 2015 were searched. Fifty-two eligible studies were identified. Missing data were very common; the median proportion of trial participants with complete cost-effectiveness data was 63% (interquartile range: 47%-81%). The most common approach for the primary analysis was to restrict analysis to those with complete data (43%), followed by multiple imputation (30%). Half of the studies conducted some sort of sensitivity analyses, but only 2 (4%) considered possible departures from the missing-at-random assumption. Further improvements are needed to address missing data in cost-effectiveness analyses conducted alongside randomised trials. These should focus on limiting the extent of missing data, choosing an appropriate method for the primary analysis that is valid under contextually plausible assumptions, and conducting sensitivity analyses to departures from the missing-at-random assumption. © 2018 The Authors Health Economics published by John Wiley & Sons Ltd.

Effects of calcium on the incidence of recurrent colorectal adenomas

PubMed Central

Veettil, Sajesh K.; Ching, Siew Mooi; Lim, Kean Ghee; Saokaew, Surasak; Phisalprapa, Pochamana; Chaiyakunapruk, Nathorn

2017-01-01

Abstract Background: Protective effects of calcium supplementation against colorectal adenomas have been documented in systematic reviews; however, the results have not been conclusive. Our objective was to update and systematically evaluate the evidence for calcium supplementation taking into consideration the risks of systematic and random error and to GRADE the evidence. Methods: The study comprised a systematic review with meta-analysis and trial sequential analysis (TSA) of randomized controlled trials (RCTs). We searched for RCTs published up until September 2016. Retrieved trials were evaluated using risk of bias. Primary outcome measures were the incidences of any recurrent adenomas and of advanced adenomas. Meta-analytic estimates were calculated with the random-effects model and random errors were evaluated with trial sequential analyses (TSAs). Results: Five randomized trials (2234 patients with a history of adenomas) were included. Two of the 5 trials showed either unclear or high risks of bias in most criteria. Meta-analysis of good quality RCTs suggest a moderate protective effect of calcium supplementation on recurrence of adenomas (relative risk [RR], 0.88 [95% CI 0.79–0.99]); however, its effects on advanced adenomas did not show statistical significance (RR, 1.02 [95% CI 0.67–1.55]). Subgroup analyses demonstrated a greater protective effect on recurrence of adenomas with elemental calcium dose ≥1600 mg/day (RR, 0.74 [95% CI 0.56–0.97]) compared to ≤1200 mg/day (RR, 0.84 [95% CI 0.73–0.97]). No major serious adverse events were associated with the use of calcium, but there was an increase in the incidence of hypercalcemia (P = .0095). TSA indicated a lack of firm evidence for a beneficial effect. Concerns with directness and imprecision rated down the quality of the evidence to “low.” Conclusion: The available good quality RCTs suggests a possible beneficial effect of calcium supplementation on the recurrence of adenomas; however, TSA indicated that the accumulated evidence is still inconclusive. Using GRADE-methodology, we conclude that the quality of evidence is low. Large well-designed randomized trials with low risk of bias are needed. PMID:28796047

Blood Pressure Reduction and Secondary Stroke Prevention: A Systematic Review and Metaregression Analysis of Randomized Clinical Trials.

PubMed

Katsanos, Aristeidis H; Filippatou, Angeliki; Manios, Efstathios; Deftereos, Spyridon; Parissis, John; Frogoudaki, Alexandra; Vrettou, Agathi-Rosa; Ikonomidis, Ignatios; Pikilidou, Maria; Kargiotis, Odysseas; Voumvourakis, Konstantinos; Alexandrov, Anne W; Alexandrov, Andrei V; Tsivgoulis, Georgios

2017-01-01

Current recommendations do not specifically address the optimal blood pressure (BP) reduction for secondary stroke prevention in patients with previous cerebrovascular events. We conducted a systematic review and metaregression analysis on the association of BP reduction with recurrent stroke and cardiovascular events using data from randomized controlled clinical trials of secondary stroke prevention. For all reported events during each eligible study period, we calculated the corresponding risk ratios to express the comparison of event occurrence risk between patients randomized to antihypertensive treatment and those randomized to placebo. On the basis of the reported BP values, we performed univariate metaregression analyses according to the achieved BP values under the random-effects model (Method of Moments) for those adverse events reported in ≥10 total subgroups of included randomized controlled clinical trials. In pairwise meta-analyses, antihypertensive treatment lowered the risk for recurrent stroke (risk ratio, 0.73; 95% confidence interval, 0.62-0.87; P<0.001), disabling or fatal stroke (risk ratio, 0.71; 95% confidence interval, 0.59-0.85; P<0.001), and cardiovascular death (risk ratio, 0.85; 95% confidence interval, 0.75-0.96; P=0.01). In metaregression analyses, systolic BP reduction was linearly related to the lower risk of recurrent stroke (P=0.049), myocardial infarction (P=0.024), death from any cause (P=0.001), and cardiovascular death (P<0.001). Similarly, diastolic BP reduction was linearly related to a lower risk of recurrent stroke (P=0.026) and all-cause mortality (P=0.009). Funnel plot inspection and Egger statistical test revealed no evidence of publication bias. The extent of BP reduction is linearly associated with the magnitude of risk reduction in recurrent cerebrovascular and cardiovascular events. Strict and aggressive BP control seems to be essential for effective secondary stroke prevention. © 2016 American Heart Association, Inc.

[Study protocol on the effect of the economic crisis on mortality and reproductive health and health inequalities in Spain].

PubMed

Pérez, Glòria; Gotsens, Mercè; Palència, Laia; Marí-Dell'Olmo, Marc; Domínguez-Berjón, M Felicitas; Rodríguez-Sanz, Maica; Puig, Vanessa; Bartoll, Xavier; Gandarillas, Ana; Martín, Unai; Bacigalupe, Amaia; Díez, Elia; Ruiz, Miguel; Esnaola, Santiago; Calvo, Montserrat; Sánchez, Pablo; Luque Fernández, Miguel Ángel; Borrell, Carme

The aim is to present the protocol of the two sub-studies on the effect of the economic crisis on mortality and reproductive health and health inequalities in Spain. Substudy 1: describe the evolution of mortality and reproductive health between 1990 and 2013 through a longitudinal ecological study in the Autonomous Communities. This study will identify changes caused by the economic crisis in trends or reproductive health and mortality indicators using panel data (17 Autonomous Communities per study year) and adjusting Poisson models with random effects variance. Substudy 2: analyse inequalities by socioeconomic deprivation in mortality and reproductive health in several areas of Spain. An ecological study analysing trends in the pre-crisis (1999-2003 and 2004-2008) and crisis (2009-2013) periods will be performed. Random effects models Besag York and Mollié will be adjusted to estimate mortality indicators softened in reproductive health and census tracts. Copyright © 2016 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

Effects of oncological care pathways in primary and secondary care on patient, professional, and health systems outcomes: protocol for a systematic review and meta-analysis.

PubMed

van Hoeve, Jolanda C; Vernooij, Robin W M; Lawal, Adegboyega K; Fiander, Michelle; Nieboer, Peter; Siesling, Sabine; Rotter, Thomas

2018-03-27

The high impact of a cancer diagnosis on patients and their families and the increasing costs of cancer treatment call for optimal and efficient oncological care. To improve the quality of care and to minimize healthcare costs and its economic burden, many healthcare organizations introduce care pathways to improve efficiency across the continuum of cancer care. However, there is limited research on the effects of cancer care pathways in different settings. The aim of this systematic review and meta-analysis described in this protocol is to synthesize existing literature on the effects of oncological care pathways. We will conduct a systematic search strategy to identify all relevant literature in several biomedical databases, including Cochrane library, MEDLINE, Embase, and CINAHL. We will follow the methodology of Cochrane Effective Practice and Organisation of Care (EPOC), and we will include randomized trials, non-randomized trials, controlled before-after studies, and interrupted time series studies. In addition, we will include full economic evaluations (cost-effectiveness analyses, cost-utility analyses, and cost-benefit analyses), cost analyses, and comparative resource utilization studies, if available. Two reviewers will independently screen all studies and evaluate those included for risk of bias. From these studies, we will extract data regarding patient, professional, and health systems outcomes. Our systematic review will follow the PRISMA set of items for reporting in systematic reviews and meta-analyses. Following the protocol outlined in this article, we aim to identify, assess, and synthesize all available evidence in order to provide an evidence base on the effects of oncological care pathways as reported in the literature. PROSPERO CRD42017057592 .

The effect of statins on erectile dysfunction: a meta-analysis of randomized trials.

PubMed

Kostis, John B; Dobrzynski, Jeanne M

2014-07-01

Erectile dysfunction (ED) is common in older men, especially those with comorbidities such as diabetes and atherosclerotic disease, conditions where statins are frequently prescribed. To examine the effect of statin therapy on ED using the five-item version of the International Inventory of Erectile Function (IIEF). We performed a random-effects meta-analysis of studies identified by a systematic search of MEDLINE, Web of Knowledge, the Cochrane Database, and ClinicalTrials.gov. Examination of the 186 retrieved citations resulted in the selection of 11 randomized trials for inclusion in the meta-analysis. Change in the IIEF score. IIEF increased by 3.4 points (95% CI 1.7-5.0, P = 0.0001) with statins compared to control. This effect remained statistically significant after multiple sensitivity analyses, including analysis for publication bias, a cumulative meta-analysis, and 11 repeated analyses with each study omitted sequentially. The increase in IIEF with statins was approximately one-third to one-half of that previously reported with phosphodiesterase-5 inhibitors and larger than the effect of lifestyle modification. Metaregression showed an increase in benefit with decreasing lipophilicity. The average age of participants and the degree of LDL cholesterol lowering did not alter the effect on IIEF. Statins cause a clinically relevant improvement of erectile function as measured by the five-item version of the IIEF. © 2014 International Society for Sexual Medicine.

MendelianRandomization: an R package for performing Mendelian randomization analyses using summarized data.

PubMed

Yavorska, Olena O; Burgess, Stephen

2017-12-01

MendelianRandomization is a software package for the R open-source software environment that performs Mendelian randomization analyses using summarized data. The core functionality is to implement the inverse-variance weighted, MR-Egger and weighted median methods for multiple genetic variants. Several options are available to the user, such as the use of robust regression, fixed- or random-effects models and the penalization of weights for genetic variants with heterogeneous causal estimates. Extensions to these methods, such as allowing for variants to be correlated, can be chosen if appropriate. Graphical commands allow summarized data to be displayed in an interactive graph, or the plotting of causal estimates from multiple methods, for comparison. Although the main method of data entry is directly by the user, there is also an option for allowing summarized data to be incorporated from the PhenoScanner database of genotype-phenotype associations. We hope to develop this feature in future versions of the package. The R software environment is available for download from [https://www.r-project.org/]. The MendelianRandomization package can be downloaded from the Comprehensive R Archive Network (CRAN) within R, or directly from [https://cran.r-project.org/web/packages/MendelianRandomization/]. Both R and the MendelianRandomization package are released under GNU General Public Licenses (GPL-2|GPL-3). © The Author 2017. Published by Oxford University Press on behalf of the International Epidemiological Association.

Complementary therapies for peripheral arterial disease: systematic review.

PubMed

Pittler, Max H; Ernst, Edzard

2005-07-01

While peripheral arterial disease (PAD) affects a considerable proportion of patients in the primary care setting, there is a high level of use of complementary treatment options. The aim was to assess the effectiveness of any type of complementary therapy for peripheral arterial disease. A systematic review was performed. Literature searches were conducted on Medline, Embase, Amed, and the Cochrane Library until December 2004. Hand-searches of medical journals and bibliographies were conducted. There were no restrictions regarding the language of publication. The screening of studies, selection, data extraction, the assessment of methodologic quality and validation were performed independently by the two reviewers. Data from randomized controlled trials, and systematic reviews and meta-analyses, which based their findings on the results of randomized controlled trials were included. Seven systematic reviews and meta-analyses and three additional randomized controlled trials met the inclusion criteria and were reviewed. The evidence relates to acupuncture, biofeedback, chelation therapy, CO(2)-applications and the dietary supplements Allium sativum (garlic), Ginkgo biloba (ginkgo), omega-3 fatty acids, padma 28 and Vitamin E. Most studies included only patients with peripheral arterial disease in Fontaine stage II (intermittent claudication). The reviewed RCTs, systematic reviews and meta-analyses which based their findings on the results of RCTs suggest that G. biloba is effective compared with placebo for patients with intermittent claudication. Evidence also suggests that padma 28 is effective for intermittent claudication, although more data are required to confirm these findings. For all other complementary treatment options there is no evidence beyond reasonable doubt to suggest effectiveness for patients with peripheral arterial disease.

Reporting of Positive Results in Randomized Controlled Trials of Mindfulness-Based Mental Health Interventions.

PubMed

Coronado-Montoya, Stephanie; Levis, Alexander W; Kwakkenbos, Linda; Steele, Russell J; Turner, Erick H; Thombs, Brett D

2016-01-01

A large proportion of mindfulness-based therapy trials report statistically significant results, even in the context of very low statistical power. The objective of the present study was to characterize the reporting of "positive" results in randomized controlled trials of mindfulness-based therapy. We also assessed mindfulness-based therapy trial registrations for indications of possible reporting bias and reviewed recent systematic reviews and meta-analyses to determine whether reporting biases were identified. CINAHL, Cochrane CENTRAL, EMBASE, ISI, MEDLINE, PsycInfo, and SCOPUS databases were searched for randomized controlled trials of mindfulness-based therapy. The number of positive trials was described and compared to the number that might be expected if mindfulness-based therapy were similarly effective compared to individual therapy for depression. Trial registries were searched for mindfulness-based therapy registrations. CINAHL, Cochrane CENTRAL, EMBASE, ISI, MEDLINE, PsycInfo, and SCOPUS were also searched for mindfulness-based therapy systematic reviews and meta-analyses. 108 (87%) of 124 published trials reported ≥1 positive outcome in the abstract, and 109 (88%) concluded that mindfulness-based therapy was effective, 1.6 times greater than the expected number of positive trials based on effect size d = 0.55 (expected number positive trials = 65.7). Of 21 trial registrations, 13 (62%) remained unpublished 30 months post-trial completion. No trial registrations adequately specified a single primary outcome measure with time of assessment. None of 36 systematic reviews and meta-analyses concluded that effect estimates were overestimated due to reporting biases. The proportion of mindfulness-based therapy trials with statistically significant results may overstate what would occur in practice.

Investigating causal associations between use of nicotine, alcohol, caffeine and cannabis: a two-sample bidirectional Mendelian randomization study.

PubMed

Verweij, Karin J H; Treur, Jorien L; Vink, Jacqueline M

2018-07-01

Epidemiological studies consistently show co-occurrence of use of different addictive substances. Whether these associations are causal or due to overlapping underlying influences remains an important question in addiction research. Methodological advances have made it possible to use published genetic associations to infer causal relationships between phenotypes. In this exploratory study, we used Mendelian randomization (MR) to examine the causality of well-established associations between nicotine, alcohol, caffeine and cannabis use. Two-sample MR was employed to estimate bidirectional causal effects between four addictive substances: nicotine (smoking initiation and cigarettes smoked per day), caffeine (cups of coffee per day), alcohol (units per week) and cannabis (initiation). Based on existing genome-wide association results we selected genetic variants associated with the exposure measure as an instrument to estimate causal effects. Where possible we applied sensitivity analyses (MR-Egger and weighted median) more robust to horizontal pleiotropy. Most MR tests did not reveal causal associations. There was some weak evidence for a causal positive effect of genetically instrumented alcohol use on smoking initiation and of cigarettes per day on caffeine use, but these were not supported by the sensitivity analyses. There was also some suggestive evidence for a positive effect of alcohol use on caffeine use (only with MR-Egger) and smoking initiation on cannabis initiation (only with weighted median). None of the suggestive causal associations survived corrections for multiple testing. Two-sample Mendelian randomization analyses found little evidence for causal relationships between nicotine, alcohol, caffeine and cannabis use. © 2018 Society for the Study of Addiction.

Iodine and mental development of children 5 years old and under: a systematic review and meta-analysis.

PubMed

Bougma, Karim; Aboud, Frances E; Harding, Kimberly B; Marquis, Grace S

2013-04-22

Several reviews and meta-analyses have examined the effects of iodine on mental development. None focused on young children, so they were incomplete in summarizing the effects on this important age group. The current systematic review therefore examined the relationship between iodine and mental development of children 5 years old and under. A systematic review of articles using Medline (1980-November 2011) was carried out. We organized studies according to four designs: (1) randomized controlled trial with iodine supplementation of mothers; (2) non-randomized trial with iodine supplementation of mothers and/or infants; (3) prospective cohort study stratified by pregnant women's iodine status; (4) prospective cohort study stratified by newborn iodine status. Average effect sizes for these four designs were 0.68 (2 RCT studies), 0.46 (8 non-RCT studies), 0.52 (9 cohort stratified by mothers' iodine status), and 0.54 (4 cohort stratified by infants' iodine status). This translates into 6.9 to 10.2 IQ points lower in iodine deficient children compared with iodine replete children. Thus, regardless of study design, iodine deficiency had a substantial impact on mental development. Methodological concerns included weak study designs, the omission of important confounders, small sample sizes, the lack of cluster analyses, and the lack of separate analyses of verbal and non-verbal subtests. Quantifying more precisely the contribution of iodine deficiency to delayed mental development in young children requires more well-designed randomized controlled trials, including ones on the role of iodized salt.

Anxiety Outcomes after Physical Activity Interventions: Meta-Analysis Findings

PubMed Central

Conn, Vicki S.

2011-01-01

Background Although numerous primary studies have documented the mental health benefits of physical activity (PA), no previous quantitative synthesis has examined anxiety outcomes of interventions to increase PA. Objectives This meta-analysis integrates extant research about anxiety outcomes from interventions to increase PA among healthy adults. Method Extensive literature searching located published and unpublished PA intervention studies with anxiety outcomes. Eligible studies reported findings from interventions designed to increase PA delivered to healthy adults without anxiety disorders. Data were coded from primary studies. Random-effects meta-analytic procedures were completed. Exploratory moderator analyses using meta-analysis ANOVA and regression analogues were conducted to determine if report, methods, sample, or intervention characteristics were associated with differences in anxiety outcomes. Results Data were synthesized across 3,289 subjects from 19 eligible reports. The overall mean anxiety effect size (d-index) for two-group comparisons was 0.22 with significant heterogeneity (Q = 32.15). Exploratory moderator analyses found larger anxiety improvement effect sizes among studies that included larger samples, used random allocation of subjects to treatment and control conditions, targeted only PA behavior instead of multiple health behaviors, included supervised exercise (vs. home-based PA), used moderate or high-intensity instead of low-intensity PA, and suggested subjects exercise at a fitness facility (vs. home) following interventions. Discussion These findings document that some interventions can decrease anxiety symptoms among healthy adults. Exploratory moderator analyses suggest possible directions for future primary research to compare interventions in randomized trials to confirm causal relationships. PMID:20410849

Mindfulness-Based Cognitive Therapy in Advanced Prostate Cancer: A Randomized Controlled Trial.

PubMed

Chambers, Suzanne K; Occhipinti, Stefano; Foley, Elizabeth; Clutton, Samantha; Legg, Melissa; Berry, Martin; Stockler, Martin R; Frydenberg, Mark; Gardiner, Robert A; Lepore, Stephen J; Davis, Ian D; Smith, David P

2017-01-20

Purpose Advanced prostate cancer (PC) is associated with substantial psychosocial morbidity. We sought to determine whether mindfulness-based cognitive therapy (MBCT) reduces distress in men with advanced PC. Methods Men with advanced PC (proven metastatic and/or castration-resistant biochemical progression) were randomly assigned to an 8-week, group-based MBCT intervention delivered by telephone (n = 94) or to minimally enhanced usual care (n = 95). Primary intervention outcomes were psychological distress, cancer-specific distress, and prostate-specific antigen anxiety. Mindfulness skills were assessed as potential mediators of effect. Participants were assessed at baseline and were followed up at 3, 6, and 9 months. Main statistical analyses were conducted on the basis of intention to treat. Results Fourteen MBCT groups were conducted in the intervention arm. Facilitator adherence ratings were high (> 93%). Using random-effects mixed-regression models, intention-to-treat analyses indicated no significant changes in intervention outcomes or in engagement with mindfulness for men in MBCT compared with those receiving minimally enhanced usual care. Per-protocol analyses also found no differences between arms in outcomes or engagement, with the exception of the mindfulness skill of observing, which increased over time for men in MBCT compared with usual care ( P = .032). Conclusion MBCT in this format was not more effective than minimally enhanced usual care in reducing distress in men with advanced PC. Future intervention research for these men should consider approaches that map more closely to masculinity.

A Family-Based Randomized Controlled Trial of Pain Intervention for Adolescents with Sickle Cell Disease

PubMed Central

Barakat, Lamia P.; Schwartz, Lisa A.; Salamon, Katherine S.; Radcliffe, Jerilynn

2010-01-01

The study had two aims--to determine the efficacy of a family-based cognitive-behavioral pain management intervention for adolescents with sickle cell disease (SCD) in (1) reducing pain and improving health-related variables and (2) improving psychosocial outcomes. Each adolescent and a family support person were randomly assigned to receive a brief pain intervention (PAIN) (n = 27) or a disease education attention control intervention (DISEASE ED) (n = 26) delivered at home. Assessment of primary pain and health-related variables (health service use, pain coping, pain-related hindrance of goals) and secondary psychosocial outcomes (disease knowledge, disease self-efficacy, and family communication) occurred at baseline (prior to randomization), post-intervention, and one-year follow-up. Change on outcomes did not differ significantly by group at either time point. When groups were combined in exploratory analyses, there was evidence of small to medium effects of intervention on health-related and psychosocial variables. Efforts to address barriers to participation and improve feasibility of psychosocial interventions for pediatric SCD are critical to advancing development of effective treatments for pain. Sample size was insufficient to adequately test efficacy, and analyses did not support this focused cognitive-behavioral pain management intervention in this sample of adolescents with SCD. Exploratory analyses suggest that comprehensive interventions, that address a broad range of skills related to disease management and adolescent health concerns, may be more effective in supporting teens during healthcare transition. PMID:20686425

Estimating causal contrasts involving intermediate variables in the presence of selection bias.

PubMed

Valeri, Linda; Coull, Brent A

2016-11-20

An important goal across the biomedical and social sciences is the quantification of the role of intermediate factors in explaining how an exposure exerts an effect on an outcome. Selection bias has the potential to severely undermine the validity of inferences on direct and indirect causal effects in observational as well as in randomized studies. The phenomenon of selection may arise through several mechanisms, and we here focus on instances of missing data. We study the sign and magnitude of selection bias in the estimates of direct and indirect effects when data on any of the factors involved in the analysis is either missing at random or not missing at random. Under some simplifying assumptions, the bias formulae can lead to nonparametric sensitivity analyses. These sensitivity analyses can be applied to causal effects on the risk difference and risk-ratio scales irrespectively of the estimation approach employed. To incorporate parametric assumptions, we also develop a sensitivity analysis for selection bias in mediation analysis in the spirit of the expectation-maximization algorithm. The approaches are applied to data from a health disparities study investigating the role of stage at diagnosis on racial disparities in colorectal cancer survival. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Lingual vs. labial fixed orthodontic appliances: systematic review and meta-analysis of treatment effects.

PubMed

Papageorgiou, Spyridon N; Gölz, Lina; Jäger, Andreas; Eliades, Theodore; Bourauel, Christoph

2016-04-01

The aim of this systematic review was to compare the therapeutic and adverse effects of lingual and labial orthodontic fixed appliances from clinical trials on human patients in an evidence-based manner. Randomized and prospective non-randomized clinical trials comparing lingual and labial appliances were included. Risk of bias within and across studies was assessed using the Cochrane tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Random-effects meta-analyses were conducted, followed by subgroup and sensitivity analyses. Six electronic databases were searched from inception to July 2015, without limitations. A total of 13 papers pertaining to 11 clinical trials were included with a total of 407 (34% male/66% female) patients. Compared with labial appliances, lingual appliances were associated with increased overall oral discomfort, increased speech impediment (measured using auditory analysis), worse speech performance assessed by laypersons, increased eating difficulty, and decreased intermolar width. On the other hand, lingual appliances were associated with increased intercanine width and significantly decreased anchorage loss of the maxillary first molar during space closure. Based on existing trials, there is insufficient evidence to make robust recommendations for lingual fixed orthodontic appliances regarding their therapeutic or adverse effects, as the quality of evidence was low. © 2016 Eur J Oral Sci.

Online Alcohol Assessment and Feedback for Hazardous and Harmful Drinkers: Findings From the AMADEUS-2 Randomized Controlled Trial of Routine Practice in Swedish Universities.

PubMed

Bendtsen, Preben; Bendtsen, Marcus; Karlsson, Nadine; White, Ian R; McCambridge, Jim

2015-07-09

Previous research on the effectiveness of online alcohol interventions for college students has shown mixed results. Small benefits have been found in some studies and because online interventions are inexpensive and possible to implement on a large scale, there is a need for further study. This study evaluated the effectiveness of national provision of a brief online alcohol intervention for students in Sweden. Risky drinkers at 9 colleges and universities in Sweden were invited by mail and identified using a single screening question. These students (N=1605) gave consent and were randomized into a 2-arm parallel group randomized controlled trial consisting of immediate or delayed access to a fully automated online assessment and intervention with personalized feedback. After 2 months, there was no strong evidence of effectiveness with no statistically significant differences in the planned analyses, although there were some indication of possible benefit in sensitivity analyses suggesting an intervention effect of a 10% reduction (95% CI -30% to 10%) in total weekly alcohol consumption. Also, differences in effect sizes between universities were seen with participants from a major university (n=365) reducing their weekly alcohol consumption by 14% (95% CI -23% to -4%). However, lower recruitment than planned and differential attrition in the intervention and control group (49% vs 68%) complicated interpretation of the outcome data. Any effects of current national provision are likely to be small and further research and development work is needed to enhance effectiveness. International Standard Randomized Controlled Trial Number (ISRCTN): 02335307; http://www.isrctn.com/ISRCTN02335307 (Archived by WebCite at http://www.webcitation.org/6ZdPUh0R4).

Comparison of Estimates between Cohort and Case-Control Studies in Meta-Analyses of Therapeutic Interventions: A Meta-Epidemiological Study.

PubMed

Lanza, Amy; Ravaud, Philippe; Riveros, Carolina; Dechartres, Agnes

2016-01-01

Observational studies are increasingly being used for assessing therapeutic interventions. Case-control studies are generally considered to have greater risk of bias than cohort studies, but we lack evidence of differences in effect estimates between the 2 study types. We aimed to compare estimates between cohort and case-control studies in meta-analyses of observational studies of therapeutic interventions by using a meta-epidemiological study. We used a random sample of meta-analyses of therapeutic interventions published in 2013 that included both cohort and case-control studies assessing a binary outcome. For each meta-analysis, the ratio of estimates (RE) was calculated by comparing the estimate in case-control studies to that in cohort studies. Then, we used random-effects meta-analysis to estimate a combined RE across meta-analyses. An RE < 1 indicated that case-control studies yielded larger estimates than cohort studies. The final analysis included 23 meta-analyses: 138 cohort and 133 case-control studies. Treatment effect estimates did not significantly differ between case-control and cohort studies (combined RE 0.97 [95% CI 0.86-1.09]). Heterogeneity was low, with between-meta-analysis variance τ2 = 0.0049. Estimates did not differ between case-control and prospective or retrospective cohort studies (RE = 1.05 [95% CI 0.96-1.15] and RE = 0.99 [95% CI, 0.83-1.19], respectively). Sensitivity analysis of studies reporting adjusted estimates also revealed no significant difference (RE = 1.03 [95% CI 0.91-1.16]). Heterogeneity was also low for these analyses. We found no significant difference in treatment effect estimates between case-control and cohort studies assessing therapeutic interventions.

Effects of Interventions on Survival in Acute Respiratory Distress Syndrome: an Umbrella Review of 159 Published Randomized Trials and 29 Meta-analyses

PubMed Central

Tonelli, Adriano R.; Zein, Joe; Adams, Jacob; Ioannidis, John P.A.

2014-01-01

Purpose Multiple interventions have been tested in acute respiratory distress syndrome (ARDS). We examined the entire agenda of published randomized controlled trials (RCTs) in ARDS that reported on mortality and of respective meta-analyses. Methods We searched PubMed, the Cochrane Library and Web of Knowledge until July 2013. We included RCTs in ARDS published in English. We excluded trials of newborns and children; and those on short-term interventions, ARDS prevention or post-traumatic lung injury. We also reviewed all meta-analyses of RCTs in this field that addressed mortality. Treatment modalities were grouped in five categories: mechanical ventilation strategies and respiratory care, enteral or parenteral therapies, inhaled / intratracheal medications, nutritional support and hemodynamic monitoring. Results We identified 159 published RCTs of which 93 had overall mortality reported (n= 20,671 patients) - 44 trials (14,426 patients) reported mortality as a primary outcome. A statistically significant survival benefit was observed in 8 trials (7 interventions) and two trials reported an adverse effect on survival. Among RTCs with >50 deaths in at least 1 treatment arm (n=21), 2 showed a statistically significant mortality benefit of the intervention (lower tidal volumes and prone positioning), 1 showed a statistically significant mortality benefit only in adjusted analyses (cisatracurium) and 1 (high-frequency oscillatory ventilation) showed a significant detrimental effect. Across 29 meta-analyses, the most consistent evidence was seen for low tidal volumes and prone positioning in severe ARDS. Conclusions There is limited supportive evidence that specific interventions can decrease mortality in ARDS. While low tidal volumes and prone positioning in severe ARDS seem effective, most sporadic findings of interventions suggesting reduced mortality are not corroborated consistently in large-scale evidence including meta-analyses. PMID:24667919

Global mean-field phase diagram of the spin-1 Ising ferromagnet in a random crystal field

NASA Astrophysics Data System (ADS)

Borelli, M. E. S.; Carneiro, C. E. I.

1996-02-01

We study the phase diagram of the mean-field spin-1 Ising ferromagnet in a uniform magnetic field H and a random crystal field Δi, with probability distribution P( Δi) = pδ( Δi - Δ) + (1 - p) δ( Δi). We analyse the effects of randomness on the first-order surfaces of the Δ- T- H phase diagram for different values of the concentration p and show how these surfaces are affected by the dilution of the crystal field.

Nicotine Replacement: Effects on Postcessation Weight Gain.

ERIC Educational Resources Information Center

Gross, Janet; And Others

1989-01-01

Examined nicotine replacement effects on postcessation weight gain in smoking cessation volunteers. Randomly assigned abstinent subjects to active nicotine or placebo gum conditions for 10 weeks. Analyses revealed strong evidence for gum effect on weight gain, with active gum users gaining mean total of 3.8 pounds compared with 7.8 pounds for…

A Comparison of Four Approaches to Account for Method Effects in Latent State-Trait Analyses

ERIC Educational Resources Information Center

Geiser, Christian; Lockhart, Ginger

2012-01-01

Latent state-trait (LST) analysis is frequently applied in psychological research to determine the degree to which observed scores reflect stable person-specific effects, effects of situations and/or person-situation interactions, and random measurement error. Most LST applications use multiple repeatedly measured observed variables as indicators…

Effect of texture randomization on the slip and interfacial robustness in turbulent flows over superhydrophobic surfaces

NASA Astrophysics Data System (ADS)

Seo, Jongmin; Mani, Ali

2018-04-01

Superhydrophobic surfaces demonstrate promising potential for skin friction reduction in naval and hydrodynamic applications. Recent developments of superhydrophobic surfaces aiming for scalable applications use random distribution of roughness, such as spray coating and etched process. However, most previous analyses of the interaction between flows and superhydrophobic surfaces studied periodic geometries that are economically feasible only in laboratory-scale experiments. In order to assess the drag reduction effectiveness as well as interfacial robustness of superhydrophobic surfaces with randomly distributed textures, we conduct direct numerical simulations of turbulent flows over randomly patterned interfaces considering a range of texture widths w+≈4 -26 , and solid fractions ϕs=11 %-25 % . Slip and no-slip boundary conditions are implemented in a pattern, modeling the presence of gas-liquid interfaces and solid elements. Our results indicate that slip of randomly distributed textures under turbulent flows is about 30 % less than those of surfaces with aligned features of the same size. In the small texture size limit w+≈4 , the slip length of the randomly distributed textures in turbulent flows is well described by a previously introduced Stokes flow solution of randomly distributed shear-free holes. By comparing DNS results for patterned slip and no-slip boundary against the corresponding homogenized slip length boundary conditions, we show that turbulent flows over randomly distributed posts can be represented by an isotropic slip length in streamwise and spanwise direction. The average pressure fluctuation on a gas pocket is similar to that of the aligned features with the same texture size and gas fraction, but the maximum interface deformation at the leading edge of the roughness element is about twice as large when the textures are randomly distributed. The presented analyses provide insights on implications of texture randomness on drag reduction performance and robustness of superhydrophobic surfaces.

Continuing or Temporarily Stopping Prestroke Antihypertensive Medication in Acute Stroke: An Individual Patient Data Meta-Analysis.

PubMed

Woodhouse, Lisa J; Manning, Lisa; Potter, John F; Berge, Eivind; Sprigg, Nikola; Wardlaw, Joanna; Lees, Kennedy R; Bath, Philip M; Robinson, Thompson G

2017-05-01

Over 50% of patients are already taking blood pressure-lowering therapy on hospital admission for acute stroke. An individual patient data meta-analysis from randomized controlled trials was undertaken to determine the effect of continuation versus temporarily stopping preexisting antihypertensive medication in acute stroke. Key databases were searched for trials against the following inclusion criteria: randomized design; stroke onset ≤48 hours; investigating the effect of continuation versus stopping prestroke antihypertensive medication; and follow-up of ≥2 weeks. Two randomized controlled trials were identified and included in this meta-analysis of individual patient data from 2860 patients with ≤48 hours of acute stroke. Risk of bias in each study was low. In adjusted logistic regression and multiple regression analyses (using random effects), we found no significant association between continuation of prestroke antihypertensive therapy (versus stopping) and risk of death or dependency at final follow-up: odds ratio 0.96 (95% confidence interval, 0.80-1.14). No significant associations were found between continuation (versus stopping) of therapy and secondary outcomes at final follow-up. Analyses for death and dependency in prespecified subgroups revealed no significant associations with continuation versus temporarily stopping therapy, with the exception of patients randomized ≤12 hours, in whom a difference favoring stopping treatment met statistical significance. We found no significant benefit with continuation of antihypertensive treatment in the acute stroke period. Therefore, there is no urgency to administer preexisting antihypertensive therapy in the first few hours or days after stroke, unless indicated for other comorbid conditions. © 2017 American Heart Association, Inc.

A Poisson approach to the validation of failure time surrogate endpoints in individual patient data meta-analyses.

PubMed

Rotolo, Federico; Paoletti, Xavier; Burzykowski, Tomasz; Buyse, Marc; Michiels, Stefan

2017-01-01

Surrogate endpoints are often used in clinical trials instead of well-established hard endpoints for practical convenience. The meta-analytic approach relies on two measures of surrogacy: one at the individual level and one at the trial level. In the survival data setting, a two-step model based on copulas is commonly used. We present a new approach which employs a bivariate survival model with an individual random effect shared between the two endpoints and correlated treatment-by-trial interactions. We fit this model using auxiliary mixed Poisson models. We study via simulations the operating characteristics of this mixed Poisson approach as compared to the two-step copula approach. We illustrate the application of the methods on two individual patient data meta-analyses in gastric cancer, in the advanced setting (4069 patients from 20 randomized trials) and in the adjuvant setting (3288 patients from 14 randomized trials).

Adaptive adjustment of the randomization ratio using historical control data

PubMed Central

Hobbs, Brian P.; Carlin, Bradley P.; Sargent, Daniel J.

2013-01-01

Background Prospective trial design often occurs in the presence of “acceptable” [1] historical control data. Typically this data is only utilized for treatment comparison in a posteriori retrospective analysis to estimate population-averaged effects in a random-effects meta-analysis. Purpose We propose and investigate an adaptive trial design in the context of an actual randomized controlled colorectal cancer trial. This trial, originally reported by Goldberg et al. [2], succeeded a similar trial reported by Saltz et al. [3], and used a control therapy identical to that tested (and found beneficial) in the Saltz trial. Methods The proposed trial implements an adaptive randomization procedure for allocating patients aimed at balancing total information (concurrent and historical) among the study arms. This is accomplished by assigning more patients to receive the novel therapy in the absence of strong evidence for heterogeneity among the concurrent and historical controls. Allocation probabilities adapt as a function of the effective historical sample size (EHSS) characterizing relative informativeness defined in the context of a piecewise exponential model for evaluating time to disease progression. Commensurate priors [4] are utilized to assess historical and concurrent heterogeneity at interim analyses and to borrow strength from the historical data in the final analysis. The adaptive trial’s frequentist properties are simulated using the actual patient-level historical control data from the Saltz trial and the actual enrollment dates for patients enrolled into the Goldberg trial. Results Assessing concurrent and historical heterogeneity at interim analyses and balancing total information with the adaptive randomization procedure leads to trials that on average assign more new patients to the novel treatment when the historical controls are unbiased or slightly biased compared to the concurrent controls. Large magnitudes of bias lead to approximately equal allocation of patients among the treatment arms. Using the proposed commensurate prior model to borrow strength from the historical data, after balancing total information with the adaptive randomization procedure, provides admissible estimators of the novel treatment effect with desirable bias-variance trade-offs. Limitations Adaptive randomization methods in general are sensitive to population drift and more suitable for trials that initiate with gradual enrollment. Balancing information among study arms in time-to-event analyses is difficult in the presence of informative right-censoring. Conclusions The proposed design could prove important in trials that follow recent evaluations of a control therapy. Efficient use of the historical controls is especially important in contexts where reliance on pre-existing information is unavoidable because the control therapy is exceptionally hazardous, expensive, or the disease is rare. PMID:23690095

Adaptive adjustment of the randomization ratio using historical control data.

PubMed

Hobbs, Brian P; Carlin, Bradley P; Sargent, Daniel J

2013-01-01

Prospective trial design often occurs in the presence of 'acceptable' historical control data. Typically, these data are only utilized for treatment comparison in a posteriori retrospective analysis to estimate population-averaged effects in a random-effects meta-analysis. We propose and investigate an adaptive trial design in the context of an actual randomized controlled colorectal cancer trial. This trial, originally reported by Goldberg et al., succeeded a similar trial reported by Saltz et al., and used a control therapy identical to that tested (and found beneficial) in the Saltz trial. The proposed trial implements an adaptive randomization procedure for allocating patients aimed at balancing total information (concurrent and historical) among the study arms. This is accomplished by assigning more patients to receive the novel therapy in the absence of strong evidence for heterogeneity among the concurrent and historical controls. Allocation probabilities adapt as a function of the effective historical sample size (EHSS), characterizing relative informativeness defined in the context of a piecewise exponential model for evaluating time to disease progression. Commensurate priors are utilized to assess historical and concurrent heterogeneity at interim analyses and to borrow strength from the historical data in the final analysis. The adaptive trial's frequentist properties are simulated using the actual patient-level historical control data from the Saltz trial and the actual enrollment dates for patients enrolled into the Goldberg trial. Assessing concurrent and historical heterogeneity at interim analyses and balancing total information with the adaptive randomization procedure lead to trials that on average assign more new patients to the novel treatment when the historical controls are unbiased or slightly biased compared to the concurrent controls. Large magnitudes of bias lead to approximately equal allocation of patients among the treatment arms. Using the proposed commensurate prior model to borrow strength from the historical data, after balancing total information with the adaptive randomization procedure, provides admissible estimators of the novel treatment effect with desirable bias-variance trade-offs. Adaptive randomization methods in general are sensitive to population drift and more suitable for trials that initiate with gradual enrollment. Balancing information among study arms in time-to-event analyses is difficult in the presence of informative right-censoring. The proposed design could prove important in trials that follow recent evaluations of a control therapy. Efficient use of the historical controls is especially important in contexts where reliance on preexisting information is unavoidable because the control therapy is exceptionally hazardous, expensive, or the disease is rare.

Perioperative ketorolac in high risk breast cancer patients. Rationale, feasibility and methodology of a prospective randomized placebo-controlled trial.

PubMed

Forget, Patrice; Berlière, Martine; van Maanen, Aline; Duhoux, Francois P; Machiels, Jean-Pascal; Coulie, Pierre G; Bouche, Gauthier; De Kock, Marc

2013-10-01

Ketorolac, a NSAID routinely used during surgery proposed to have anticancer effects, is a promising way to improve postoperative oncological outcome. This effect may be particularly prominent in patients with elevated preoperative inflammatory scores, like the neutrophil:lymphocyte ratio. In this paper, we describe the rationale, the preliminary analyses in our patients, the feasibility and the methodology of a prospective randomized trial called "Ketorolac in Breast Cancer trial" (KBCt) (NCT01806259). Copyright © 2013 Elsevier Ltd. All rights reserved.

From Protocols to Publications: A Study in Selective Reporting of Outcomes in Randomized Trials in Oncology

PubMed Central

Raghav, Kanwal Pratap Singh; Mahajan, Sminil; Yao, James C.; Hobbs, Brian P.; Berry, Donald A.; Pentz, Rebecca D.; Tam, Alda; Hong, Waun K.; Ellis, Lee M.; Abbruzzese, James; Overman, Michael J.

2015-01-01

Purpose The decision by journals to append protocols to published reports of randomized trials was a landmark event in clinical trial reporting. However, limited information is available on how this initiative effected transparency and selective reporting of clinical trial data. Methods We analyzed 74 oncology-based randomized trials published in Journal of Clinical Oncology, the New England Journal of Medicine, and The Lancet in 2012. To ascertain integrity of reporting, we compared published reports with their respective appended protocols with regard to primary end points, nonprimary end points, unplanned end points, and unplanned analyses. Results A total of 86 primary end points were reported in 74 randomized trials; nine trials had greater than one primary end point. Nine trials (12.2%) had some discrepancy between their planned and published primary end points. A total of 579 nonprimary end points (median, seven per trial) were planned, of which 373 (64.4%; median, five per trial) were reported. A significant positive correlation was found between the number of planned and nonreported nonprimary end points (Spearman r = 0.66; P < .001). Twenty-eight studies (37.8%) reported a total of 65 unplanned end points; 52 (80.0%) of which were not identified as unplanned. Thirty-one (41.9%) and 19 (25.7%) of 74 trials reported a total of 52 unplanned analyses involving primary end points and 33 unplanned analyses involving nonprimary end points, respectively. Studies reported positive unplanned end points and unplanned analyses more frequently than negative outcomes in abstracts (unplanned end points odds ratio, 6.8; P = .002; unplanned analyses odd ratio, 8.4; P = .007). Conclusion Despite public and reviewer access to protocols, selective outcome reporting persists and is a major concern in the reporting of randomized clinical trials. To foster credible evidence-based medicine, additional initiatives are needed to minimize selective reporting. PMID:26304898

Assessing the treatment effect in a randomized controlled trial with extensive non-adherence: the EVOLVE trial.

PubMed

Kubo, Yumi; Sterling, Lulu Ren; Parfrey, Patrick S; Gill, Karminder; Mahaffey, Kenneth W; Gioni, Ioanna; Trotman, Marie-Louise; Dehmel, Bastian; Chertow, Glenn M

2015-01-01

Intention-to-treat (ITT) analysis is widely used to establish efficacy in randomized clinical trials. However, in a long-term outcomes study where non-adherence to study drug is substantial, the on-treatment effect of the study drug may be underestimated using the ITT analysis. The analyses presented herein are from the EVOLVE trial, a double-blind, placebo-controlled, event-driven cardiovascular outcomes study conducted to assess whether a treatment regimen including cinacalcet compared with placebo in addition to other conventional therapies reduces the risk of mortality and major cardiovascular events in patients receiving hemodialysis with secondary hyperparathyroidism. Pre-specified sensitivity analyses were performed to assess the impact of non-adherence on the estimated effect of cinacalcet. These analyses included lag-censoring, inverse probability of censoring weights (IPCW), rank preserving structural failure time model (RPSFTM) and iterative parameter estimation (IPE). The relative hazard (cinacalcet versus placebo) of mortality and major cardiovascular events was 0.93 (95% confidence interval 0.85, 1.02) using the ITT analysis; 0.85 (0.76, 0.95) using lag-censoring analysis; 0.81 (0.70, 0.92) using IPCW; 0.85 (0.66, 1.04) using RPSFTM and 0.85 (0.75, 0.96) using IPE. These analyses, while not providing definitive evidence, suggest that the intervention may have an effect while subjects are receiving treatment. The ITT method remains the established method to evaluate efficacy of a new treatment; however, additional analyses should be considered to assess the on-treatment effect when substantial non-adherence to study drug is expected or observed. Copyright © 2015 John Wiley & Sons, Ltd.

Evaluation of Evidence of Statistical Support and Corroboration of Subgroup Claims in Randomized Clinical Trials.

PubMed

Wallach, Joshua D; Sullivan, Patrick G; Trepanowski, John F; Sainani, Kristin L; Steyerberg, Ewout W; Ioannidis, John P A

2017-04-01

Many published randomized clinical trials (RCTs) make claims for subgroup differences. To evaluate how often subgroup claims reported in the abstracts of RCTs are actually supported by statistical evidence (P < .05 from an interaction test) and corroborated by subsequent RCTs and meta-analyses. This meta-epidemiological survey examines data sets of trials with at least 1 subgroup claim, including Subgroup Analysis of Trials Is Rarely Easy (SATIRE) articles and Discontinuation of Randomized Trials (DISCO) articles. We used Scopus (updated July 2016) to search for English-language articles citing each of the eligible index articles with at least 1 subgroup finding in the abstract. Articles with a subgroup claim in the abstract with or without evidence of statistical heterogeneity (P < .05 from an interaction test) in the text and articles attempting to corroborate the subgroup findings. Study characteristics of trials with at least 1 subgroup claim in the abstract were recorded. Two reviewers extracted the data necessary to calculate subgroup-level effect sizes, standard errors, and the P values for interaction. For individual RCTs and meta-analyses that attempted to corroborate the subgroup findings from the index articles, trial characteristics were extracted. Cochran Q test was used to reevaluate heterogeneity with the data from all available trials. The number of subgroup claims in the abstracts of RCTs, the number of subgroup claims in the abstracts of RCTs with statistical support (subgroup findings), and the number of subgroup findings corroborated by subsequent RCTs and meta-analyses. Sixty-four eligible RCTs made a total of 117 subgroup claims in their abstracts. Of these 117 claims, only 46 (39.3%) in 33 articles had evidence of statistically significant heterogeneity from a test for interaction. In addition, out of these 46 subgroup findings, only 16 (34.8%) ensured balance between randomization groups within the subgroups (eg, through stratified randomization), 13 (28.3%) entailed a prespecified subgroup analysis, and 1 (2.2%) was adjusted for multiple testing. Only 5 (10.9%) of the 46 subgroup findings had at least 1 subsequent pure corroboration attempt by a meta-analysis or an RCT. In all 5 cases, the corroboration attempts found no evidence of a statistically significant subgroup effect. In addition, all effect sizes from meta-analyses were attenuated toward the null. A minority of subgroup claims made in the abstracts of RCTs are supported by their own data (ie, a significant interaction effect). For those that have statistical support (P < .05 from an interaction test), most fail to meet other best practices for subgroup tests, including prespecification, stratified randomization, and adjustment for multiple testing. Attempts to corroborate statistically significant subgroup differences are rare; when done, the initially observed subgroup differences are not reproduced.

Does the use of consumer health information technology improve outcomes in the patient self-management of diabetes? A meta-analysis and narrative review of randomized controlled trials.

PubMed

Or, Calvin K L; Tao, Da

2014-05-01

To assess whether the use of consumer health information technologies (CHITs) improves outcomes in the patient self-management of diabetes. The evidence from randomized controlled trials (RCTs) on the effects of CHITs on patient outcomes was analyzed using either meta-analysis or a narrative synthesis approach. A systematic search of seven electronic databases was conducted to identify relevant reports of RCTs for the analysis. In the meta-analyses, standardized mean differences in patient outcomes were calculated and random-effects models were applied in cases where the heterogeneity of the results was moderate or high, otherwise fixed-effects models were used. Sixty-two studies, representing 67 RCTs, met the inclusion criteria. The results of the meta-analyses showed that the use of CHITs was associated with significant reductions in HbA1c, blood pressure, total cholesterol, and triglycerides levels when compared with the usual care. The findings from the narrative synthesis indicated that only a small proportion of the trials reported positive effects of CHITs on patient outcomes. The use of CHITs in supporting diabetes self-management appears to have potential benefits for patients' self-management of diabetes. However, the effectiveness of the technologies in improving patient outcomes still awaits confirmation in future studies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A systematic review and meta-analysis: Effectiveness of internet empowerment-based self-management interventions on adults with metabolic diseases.

PubMed

Kuo, Chia-Chi; Su, Yu-Jen; Lin, Chiu-Chu

2018-03-25

To synthesize the effects of Internet empowerment-based self-management interventions on adults with metabolic diseases. Metabolic diseases are prevalent and burden healthcare systems; they have become a major health problem worldwide. The effects of IESMIs on lifestyle changes have been shown to improve adults' physiological and psychological conditions. However, we found no systematic review evaluating these effects. Systematic review and meta-analysis of randomized and non-randomized controlled trials, conducted according to the Cochrane handbook. A literature search was conducted using the Airiti Library, Association for Computing Machinery, CINAHL, Cochrane Library, Embase, ProQuest, PubMed/MEDLINE and Index of the Taiwan Periodical Literature System databases (earliest-June 2016). Two reviewers used the Cochrane Collaboration bias assessment tool to assess the methodological quality of included studies. Extracted data were entered and analysed using RevMan 5.3.5 software. Inverse variance was used to estimate effect sizes. Weighted and standardized mean differences with 95% confidence intervals were calculated using a random effects model. Subgroup and sensitivity analyses were performed. Twenty-one randomized controlled trials were reviewed. Meta-analysis showed that the intervention significantly improved adults' exercise habits, glycated haemoglobin (HbA1c) levels, body weight, empowerment levels and quality of life. The intervention significantly improve the health status of adults with metabolic diseases, in particular their exercise habits, HbA1c levels, body weight, empowerment and quality of life. The intervention provides more convenient and faster access to healthcare for busy individuals with time constraints. These results suggest that healthcare professionals could develop accessible and friendly interactive online interfaces for patients to expand the use of these interventions in the clinical setting. © 2018 John Wiley & Sons Ltd.

Acupuncture and related therapies used as add-on or alternative to prokinetics for functional dyspepsia: overview of systematic reviews and network meta-analysis.

PubMed

Ho, Robin S T; Chung, Vincent C H; Wong, Charlene H L; Wu, Justin C Y; Wong, Samuel Y S; Wu, Irene X Y

2017-09-04

Prokinetics for functional dyspepsia (FD) have relatively higher number needed to treat values. Acupuncture and related therapies could be used as add-on or alternative. An overview of systematic reviews (SRs) and network meta-analyses (NMA) were performed to evaluate the comparative effectiveness of different acupuncture and related therapies. We conducted a comprehensive literature search for SRs of randomized controlled trials (RCTs) in eight international and Chinese databases. Data from eligible RCTs were extracted for random effect pairwise meta-analyses. NMA was used to explore the most effective treatment among acupuncture and related therapies used alone or as add-on to prokinetics, compared to prokinetics alone. From five SRs, 22 RCTs assessing various acupuncture and related therapies were included. No serious adverse events were reported. Two pairwise meta-analyses showed manual acupuncture has marginally stronger effect in alleviating global FD symptoms, compared to domperidone or itopride. Results from NMA showed combination of manual acupuncture and clebopride has the highest probability in alleviating patient reported global FD symptom. Combination of manual acupuncture and clebopride has the highest probability of being the most effective treatment for FD symptoms. Patients who are contraindicated for prokinetics may use manual acupuncture or moxibustion as alternative. Future confirmatory comparative effectiveness trials should compare clebopride add-on manual acupuncture with domperidone add-on manual acupuncture and moxibustion.

Juvenile Diversion: An Experimental Analysis of Effectiveness.

ERIC Educational Resources Information Center

Severy, Lawrence J.; Whitaker, J. Michael

1982-01-01

The desirability of combining tests of theory with evaluations of treatment modalities is argued in an investigation of the effectiveness of a juvenile diversion program. Using a true experimental design (with randomization), recidivism analyses dependent on court record data failed to demonstrate the relative superiority of any of three treatment…

An evidence-based review of pregabalin for the treatment of fibromyalgia.

PubMed

Arnold, Lesley M; Choy, Ernest; Clauw, Daniel J; Oka, Hiroshi; Whalen, Ed; Semel, David; Pauer, Lynne; Knapp, Lloyd

2018-04-16

Pregabalin, an α2-δ agonist, is approved for the treatment of fibromyalgia (FM) in the United States, Japan, and 37 other countries. The purpose of this article was to provide an in-depth, evidence-based summary of pregabalin for FM as demonstrated in randomized, placebo-controlled clinical studies, including open-label extensions, meta-analyses, combination studies and post-hoc analyses of clinical study data. PubMed was searched using the term "pregabalin AND fibromyalgia" and the Cochrane Library with the term "pregabalin". Both searches were conducted on 2 March 2017 with no other date limits set. Eleven randomized, double-blind, placebo-controlled clinical studies were identified including parallel group, two-way crossover and randomized withdrawal designs. One was a neuroimaging study. Five open-label extensions were also identified. Evidence of efficacy was demonstrated across the studies identified with significant and clinically relevant improvements in pain, sleep quality and patient status. The safety and tolerability profile of pregabalin is consistent across all the studies identified, including in adolescents, with dizziness and somnolence the most common adverse events reported. These efficacy and safety data are supported by meta-analyses (13 studies). Pregabalin in combination with other pharmacotherapies (7 studies) is also efficacious. Post-hoc analyses have demonstrated the onset of pregabalin efficacy as early as 1-2 days after starting treatment, examined the effect of pregabalin on other aspects of sleep beyond quality, and shown it is effective irrespective of the presence of a wide variety of patient demographic and clinical characteristics. Pregabalin is a treatment option for FM; its clinical utility has been comprehensively demonstrated.

Early outcome of early-goal directed therapy for patients with sepsis or septic shock: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Chen, Xiaofan; Zhu, Weifeng; Tan, Jing; Nie, Heyun; Liu, Liangming; Yan, Dongmei; Zhou, Xu; Sun, Xin

2017-04-18

Various trials and meta-analyses have reported conflicting results concerning the application of early goal-directed therapy (EGDT) for sepsis and septic shock. The aim of this study was to update the evidence by performing a systematic review and meta-analysis. Multiple databases were searched from initial through August, 2016 for randomized controlled trials (RCTs) which investigated the associations between the use of EGDT and mortality in patients with sepsis or septic shock. Meta-analysis was performed using random-effects model and heterogeneity was examined through subgroup analyses. The primary outcome of interest was patient all-cause mortality including hospital or ICU mortality. Seventeen RCTs including 6207 participants with 3234 in the EGDT group and 2973 in the control group were eligible for this study. Meta-analysis showed that EGDT did not significantly reduce hospital or intensive care unit (ICU) mortality (relative risk [RR] 0.89, 95% CI 0.78 to 1.02) compared with control group for patients with sepsis or septic shock. The findings of subgroup analyses stratified by study region, number of research center, year of enrollment, clinical setting, sample size, timing of EGDT almost remained constant with that of the primary analysis. Our findings provide evidence that EGDT offers neutral survival effects for patients with sepsis or septic shock. Further meta-analyses based on larger well-designed RCTs or individual patient data meta-analysis are required to explore the survival benefits of EDGT in patients with sepsis or septic shock.

Cost-Effectiveness of a Biodegradable Compared to a Titanium Fixation System in Maxillofacial Surgery: A Multicenter Randomized Controlled Trial

PubMed Central

van Bakelen, N. B.; Vermeulen, K. M.; Buijs, G. J.; Jansma, J.; de Visscher, J. G. A. M.; Hoppenreijs, Th. J. M.; Bergsma, J. E.; Stegenga, B.; Bos, R. R. M.

2015-01-01

Background Biodegradable fixation systems could reduce/delete the problems associated with titanium plate removal. This means less surgical discomfort, and a reduction in costs. Aim The aim of the present study was to compare the cost-effectiveness between a biodegradable and a titanium system in Maxillofacial surgery. Materials and Methods This multicenter RCT was performed in the Netherlands from December 2006 to July 2009. Included were 230 patients who underwent a bilateral sagittal split osteotomy (BSSO), a Le Fort-I osteotomy, or a bi-maxillary osteotomy and those treated for fractures of the mandible, maxilla, or zygoma. The patients were randomly assigned to a titanium group (KLS Martin) or to a biodegradable group (Inion CPS). Costs were assessed from a societal perspective. Health outcomes in the incremental cost-effectiveness ratio (ICER) were bone healing (8 weeks) and plate removal (2 years). Results In 25 out of the 117 patients who were randomized to the biodegradable group, the maxillofacial surgeon made the decision to switch to the titanium system intra-operatively. This resulted in an Intention-To-Treat (ITT-)analysis and a Treatment-Received (TR-) analysis. Both analyses indicated that operations performed with titanium plates and screws had better health outcomes. In the TR-analysis the costs were lower in the biodegradable group, in the ITT-analysis costs were lower in the titanium group. Conclusion and Discussion The difference in costs between the ITT and the TR analyses can be explained by the intra-operative switches: In the TR-analysis the switches were analysed in the titanium group. In the ITT-analysis they were analysed in the biodegradable group. Considering the cost-effectiveness the titanium system is preferable to the biodegradable system in the regular treatment spectrum of mandibular, Le Fort-I, and zygomatic fractures, and BSSO’s, Le Fort-I osteotomies and bimaxillary osteotomies. Trial Registration Controlled-Trials.com ISRCTN 44212338 PMID:26192813

What affects response rates in primary healthcare-based programmes? An analysis of individual and unit-related factors associated with increased odds of non-response based on HCV screening in the general population in Poland

PubMed Central

Parda, Natalia; Stępień, Małgorzata; Zakrzewska, Karolina; Madaliński, Kazimierz; Kołakowska, Agnieszka; Godzik, Paulina; Rosińska, Magdalena

2016-01-01

Objectives Response rate in public health programmes may be a limiting factor. It is important to first consider their delivery and acceptability for the target. This study aimed at determining individual and unit-related factors associated with increased odds of non-response based on hepatitis C virus screening in primary healthcare. Design Primary healthcare units (PHCUs) were extracted from the Register of Health Care Centres. Each of the PHCUs was to enrol adult patients selected on a random basis. Data on the recruitment of PHCUs and patients were analysed. Multilevel modelling was applied to investigate individual and unit-related factors associated with non-response. Multilevel logistic model was developed with fixed effects and only a random intercept for the unit. Preliminary analysis included a random effect for unit and each of the individual or PHCU covariates separately. For each of the PHCU covariates, we applied a two-level model with individual covariates, unit random effect and a single fixed effect of this unit covariate. Setting This study was conducted in primary care units in selected provinces in Poland. Participants A total of 242 PHCUs and 24 480 adults were invited. Of them, 44 PHCUs and 20 939 patients agreed to participate. Both PHCUs and patients were randomly selected. Results Data on 44 PHCUs and 24 480 patients were analysed. PHCU-level factors and recruitment strategies were important predictors of non-response. Unit random effect was significant in all models. Larger and private units reported higher non-response rates, while for those with a history of running public health programmes the odds of non-response was lower. Proactive recruitment, more working hours devoted to the project and patient resulted in higher acceptance of the project. Higher number of personnel had no such effect. Conclusions Prior to the implementation of public health programme, several factors that could hinder its execution should be addressed. PMID:27927665

What affects response rates in primary healthcare-based programmes? An analysis of individual and unit-related factors associated with increased odds of non-response based on HCV screening in the general population in Poland.

PubMed

Parda, Natalia; Stępień, Małgorzata; Zakrzewska, Karolina; Madaliński, Kazimierz; Kołakowska, Agnieszka; Godzik, Paulina; Rosińska, Magdalena

2016-12-07

Response rate in public health programmes may be a limiting factor. It is important to first consider their delivery and acceptability for the target. This study aimed at determining individual and unit-related factors associated with increased odds of non-response based on hepatitis C virus screening in primary healthcare. Primary healthcare units (PHCUs) were extracted from the Register of Health Care Centres. Each of the PHCUs was to enrol adult patients selected on a random basis. Data on the recruitment of PHCUs and patients were analysed. Multilevel modelling was applied to investigate individual and unit-related factors associated with non-response. Multilevel logistic model was developed with fixed effects and only a random intercept for the unit. Preliminary analysis included a random effect for unit and each of the individual or PHCU covariates separately. For each of the PHCU covariates, we applied a two-level model with individual covariates, unit random effect and a single fixed effect of this unit covariate. This study was conducted in primary care units in selected provinces in Poland. A total of 242 PHCUs and 24 480 adults were invited. Of them, 44 PHCUs and 20 939 patients agreed to participate. Both PHCUs and patients were randomly selected. Data on 44 PHCUs and 24 480 patients were analysed. PHCU-level factors and recruitment strategies were important predictors of non-response. Unit random effect was significant in all models. Larger and private units reported higher non-response rates, while for those with a history of running public health programmes the odds of non-response was lower. Proactive recruitment, more working hours devoted to the project and patient resulted in higher acceptance of the project. Higher number of personnel had no such effect. Prior to the implementation of public health programme, several factors that could hinder its execution should be addressed. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Statistical parameters of random heterogeneity estimated by analysing coda waves based on finite difference method

NASA Astrophysics Data System (ADS)

Emoto, K.; Saito, T.; Shiomi, K.

2017-12-01

Short-period (<1 s) seismograms are strongly affected by small-scale (<10 km) heterogeneities in the lithosphere. In general, short-period seismograms are analysed based on the statistical method by considering the interaction between seismic waves and randomly distributed small-scale heterogeneities. Statistical properties of the random heterogeneities have been estimated by analysing short-period seismograms. However, generally, the small-scale random heterogeneity is not taken into account for the modelling of long-period (>2 s) seismograms. We found that the energy of the coda of long-period seismograms shows a spatially flat distribution. This phenomenon is well known in short-period seismograms and results from the scattering by small-scale heterogeneities. We estimate the statistical parameters that characterize the small-scale random heterogeneity by modelling the spatiotemporal energy distribution of long-period seismograms. We analyse three moderate-size earthquakes that occurred in southwest Japan. We calculate the spatial distribution of the energy density recorded by a dense seismograph network in Japan at the period bands of 8-16 s, 4-8 s and 2-4 s and model them by using 3-D finite difference (FD) simulations. Compared to conventional methods based on statistical theories, we can calculate more realistic synthetics by using the FD simulation. It is not necessary to assume a uniform background velocity, body or surface waves and scattering properties considered in general scattering theories. By taking the ratio of the energy of the coda area to that of the entire area, we can separately estimate the scattering and the intrinsic absorption effects. Our result reveals the spectrum of the random inhomogeneity in a wide wavenumber range including the intensity around the corner wavenumber as P(m) = 8πε2a3/(1 + a2m2)2, where ε = 0.05 and a = 3.1 km, even though past studies analysing higher-frequency records could not detect the corner. Finally, we estimate the intrinsic attenuation by modelling the decay rate of the energy. The method proposed in this study is suitable for quantifying the statistical properties of long-wavelength subsurface random inhomogeneity, which leads the way to characterizing a wider wavenumber range of spectra, including the corner wavenumber.

Using Audit Information to Adjust Parameter Estimates for Data Errors in Clinical Trials

PubMed Central

Shepherd, Bryan E.; Shaw, Pamela A.; Dodd, Lori E.

2013-01-01

Background Audits are often performed to assess the quality of clinical trial data, but beyond detecting fraud or sloppiness, the audit data is generally ignored. In earlier work using data from a non-randomized study, Shepherd and Yu (2011) developed statistical methods to incorporate audit results into study estimates, and demonstrated that audit data could be used to eliminate bias. Purpose In this manuscript we examine the usefulness of audit-based error-correction methods in clinical trial settings where a continuous outcome is of primary interest. Methods We demonstrate the bias of multiple linear regression estimates in general settings with an outcome that may have errors and a set of covariates for which some may have errors and others, including treatment assignment, are recorded correctly for all subjects. We study this bias under different assumptions including independence between treatment assignment, covariates, and data errors (conceivable in a double-blinded randomized trial) and independence between treatment assignment and covariates but not data errors (possible in an unblinded randomized trial). We review moment-based estimators to incorporate the audit data and propose new multiple imputation estimators. The performance of estimators is studied in simulations. Results When treatment is randomized and unrelated to data errors, estimates of the treatment effect using the original error-prone data (i.e., ignoring the audit results) are unbiased. In this setting, both moment and multiple imputation estimators incorporating audit data are more variable than standard analyses using the original data. In contrast, in settings where treatment is randomized but correlated with data errors and in settings where treatment is not randomized, standard treatment effect estimates will be biased. And in all settings, parameter estimates for the original, error-prone covariates will be biased. Treatment and covariate effect estimates can be corrected by incorporating audit data using either the multiple imputation or moment-based approaches. Bias, precision, and coverage of confidence intervals improve as the audit size increases. Limitations The extent of bias and the performance of methods depend on the extent and nature of the error as well as the size of the audit. This work only considers methods for the linear model. Settings much different than those considered here need further study. Conclusions In randomized trials with continuous outcomes and treatment assignment independent of data errors, standard analyses of treatment effects will be unbiased and are recommended. However, if treatment assignment is correlated with data errors or other covariates, naive analyses may be biased. In these settings, and when covariate effects are of interest, approaches for incorporating audit results should be considered. PMID:22848072

Male circumcision and HIV infection risk.

PubMed

Krieger, John N

2012-02-01

Male circumcision is being promoted to reduce human immunodeficiency virus type 1 (HIV) infection rates. This review evaluates the scientific evidence suggesting that male circumcision reduces HIV infection risk in high-risk heterosexual populations. We followed the updated International Consultation on Urological Diseases evidence-based medicine recommendations to critically review the scientific evidence on male circumcision and HIV infection risk. Level 1 evidence supports the concept that male circumcision substantially reduces the risk of HIV infection. Three major lines of evidence support this conclusion: biological data suggesting that this concept is plausible, data from observational studies supported by high-quality meta-analyses, and three randomized clinical trials supported by high-quality meta-analyses. The evidence from these biological studies, observational studies, randomized controlled clinical trials, meta-analyses, and cost-effectiveness studies is conclusive. The challenges to implementation of male circumcision as a public health measure in high-risk populations must now be faced.

The Effects of Schema-Broadening Instruction on Second Graders’ Word-Problem Performance and Their Ability to Represent Word Problems with Algebraic Equations: A Randomized Control Study

PubMed Central

Fuchs, Lynn S.; Zumeta, Rebecca O.; Schumacher, Robin Finelli; Powell, Sarah R.; Seethaler, Pamela M.; Hamlett, Carol L.; Fuchs, Douglas

2010-01-01

The purpose of this study was to assess the effects of schema-broadening instruction (SBI) on second graders’ word-problem-solving skills and their ability to represent the structure of word problems using algebraic equations. Teachers (n = 18) were randomly assigned to conventional word-problem instruction or SBI word-problem instruction, which taught students to represent the structural, defining features of word problems with overarching equations. Intervention lasted 16 weeks. We pretested and posttested 270 students on measures of word-problem skill; analyses that accounted for the nested structure of the data indicated superior word-problem learning for SBI students. Descriptive analyses of students’ word-problem work indicated that SBI helped students represent the structure of word problems with algebraic equations, suggesting that SBI promoted this aspect of students’ emerging algebraic reasoning. PMID:20539822

How Efficacious is Danshen (Salvia miltiorrhiza) Dripping Pill in Treating Angina Pectoris? Evidence Assessment for Meta-Analysis of Randomized Controlled Trials.

PubMed

Jia, Yongliang; Leung, Siu-Wai

2017-09-01

More than 230 randomized controlled trials (RCTs) of danshen dripping pill (DSP) and isosorbide dinitrate (ISDN) in treating angina pectoris after the first preferred reporting items for systematic reviews and meta-analyses-compliant comprehensive meta-analysis were published in 2010. Other meta-analyses had flaws in study selection, statistical meta-analysis, and evidence assessment. This study completed the meta-analysis with an extensive assessment of the evidence. RCTs published from 1994 to 2016 on DSP and ISDN in treating angina pectoris for at least 4 weeks were included. The risk of bias (RoB) of included RCTs was assessed with the Cochrane's tool for assessing RoB. Meta-analyses based on a random-effects model were performed on two outcome measures: symptomatic (SYM) and electrocardiography (ECG) improvements. Subgroup analysis, sensitivity analysis, metaregression, and publication bias analysis were also conducted. The evidence strength was evaluated with the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) method. Among the included 109 RCTs with 11,973 participants, 49 RCTs and 5042 participants were new (after 2010). The RoB of included RCTs was high in randomization and blinding. Overall effect sizes in odds ratios for DSP over ISDN were 2.94 (95% confidence interval [CI]: 2.53-3.41) on SYM (n = 108) and 2.37 (95% CI: 2.08-2.69) by ECG (n = 81) with significant heterogeneities (I 2  = 41%, p < 0.0001 on SYM and I 2  = 44%, p < 0.0001 on ECG). Subgroup, sensitivity, and metaregression analyses showed consistent results without publication bias. However, the evidence strength was low in GRADE. The efficacy of DSP was still better than ISDN in treating angina pectoris, but the confidence decreased due to high RoB and heterogeneities.

Supplemental oxygen therapy does not affect the systemic inflammatory response to acute myocardial infarction.

PubMed

Hofmann, R; Tornvall, P; Witt, N; Alfredsson, J; Svensson, L; Jonasson, L; Nilsson, L

2018-04-01

Oxygen therapy has been used routinely in normoxemic patients with suspected acute myocardial infarction (AMI) despite limited evidence supporting a beneficial effect. AMI is associated with a systemic inflammation. Here, we hypothesized that the inflammatory response to AMI is potentiated by oxygen therapy. The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) multicentre trial randomized patients with suspected AMI to receive oxygen at 6 L min -1 for 6-12 h or ambient air. For this prespecified subgroup analysis, we recruited patients with confirmed AMI from two sites for evaluation of inflammatory biomarkers at randomization and 5-7 h later. Ninety-two inflammatory biomarkers were analysed using proximity extension assay technology, to evaluate the effect of oxygen on the systemic inflammatory response to AMI. Plasma from 144 AMI patients was analysed whereof 76 (53%) were randomized to oxygen and 68 (47%) to air. Eight biomarkers showed a significant increase, whereas 13 were decreased 5-7 h after randomization. The inflammatory response did not differ between the two treatment groups neither did plasma troponin T levels. After adjustment for increase in troponin T over time, age and sex, the release of inflammation-related biomarkers was still similar in the groups. In a randomized controlled setting of normoxemic patients with AMI, the use of supplemental oxygen did not have any significant impact on the early release of systemic inflammatory markers. © 2017 The Association for the Publication of the Journal of Internal Medicine.

Association of residential dampness and mold with respiratory tract infections and bronchitis: a meta-analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fisk, William J.; Eliseeva, Ekaterina A.; Mendell, Mark J.

Dampness and mold have been shown in qualitative reviews to be associated with a variety of adverse respiratory health effects, including respiratory tract infections. Several published meta-analyses have provided quantitative summaries for some of these associations, but not for respiratory infections. Demonstrating a causal relationship between dampness-related agents, which are preventable exposures, and respiratory tract infections would suggest important new public health strategies. We report the results of quantitative meta-analyses of published studies that examined the association of dampness or mold in homes with respiratory infections and bronchitis. For primary studies meeting eligibility criteria, we transformed reported odds ratios (ORs)more » and confidence intervals (CIs) to the log scale. Both fixed and random effects models were applied to the log ORs and their variances. Most studies contained multiple estimated ORs. Models accounted for the correlation between multiple results within the studies analyzed. One set of analyses was performed with all eligible studies, and another set restricted to studies that controlled for age, gender, smoking, and socioeconomic status. Subgroups of studies were assessed to explore heterogeneity. Funnel plots were used to assess publication bias. The resulting summary estimates of ORs from random effects models based on all studies ranged from 1.38 to 1.50, with 95% CIs excluding the null in all cases. Use of different analysis models and restricting analyses based on control of multiple confounding variables changed findings only slightly. ORs (95% CIs) from random effects models using studies adjusting for major confounding variables were, for bronchitis, 1.45 (1.32-1.59); for respiratory infections, 1.44 (1.31-1.59); for respiratory infections excluding nonspecific upper respiratory infections, 1.50 (1.32-1.70), and for respiratory infections in children or infants, 1.48 (1.33-1.65). Little effect of publication bias was evident. Estimated attributable risk proportions ranged from 8% to 20%. Residential dampness and mold are associated with substantial and statistically significant increases in both respiratory infections and bronchitis. If these associations were confirmed as causal, effective control of dampness and mold in buildings would prevent a substantial proportion of respiratory infections.« less

Raloxifene for women with Alzheimer disease: A randomized controlled pilot trial.

PubMed

Henderson, Victor W; Ala, Tom; Sainani, Kristin L; Bernstein, Allan L; Stephenson, B Sue; Rosen, Allyson C; Farlow, Martin R

2015-12-01

To determine whether raloxifene, a selective estrogen receptor modulator, improves cognitive function compared with placebo in women with Alzheimer disease (AD) and to provide an estimate of cognitive effect. This pilot study was conducted as a randomized, double-blind, placebo-controlled trial, with a planned treatment of 12 months. Women with late-onset AD of mild to moderate severity were randomly allocated to high-dose (120 mg) oral raloxifene or identical placebo provided once daily. The primary outcome compared between treatment groups at 12 months was change in the Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS-cog). Forty-two women randomized to raloxifene or placebo were included in intent-to-treat analyses (mean age 76 years, range 68-84), and 39 women contributed 12-month outcomes. ADAS-cog change scores at 12 months did not differ significantly between treatment groups (standardized difference 0.03, 95% confidence interval -0.39 to 0.44, 2-tailed p = 0.89). Raloxifene and placebo groups did not differ significantly on secondary analyses of dementia rating, activities of daily living, behavior, or a global cognition composite score. Caregiver burden and caregiver distress were similar in both groups. Results on the primary outcome showed no cognitive benefits in the raloxifene-treated group. This study provides Class I evidence that for women with AD, raloxifene does not have a significant cognitive effect. The study lacked the precision to exclude a small effect. © 2015 American Academy of Neurology.

Randomized trial of parent training to prevent adolescent problem behaviors during the high school transition.

PubMed

Mason, W Alex; Fleming, Charles B; Gross, Thomas J; Thompson, Ronald W; Parra, Gilbert R; Haggerty, Kevin P; Snyder, James J

2016-12-01

This randomized controlled trial tested a widely used general parent training program, Common Sense Parenting (CSP), with low-income 8th graders and their families to support a positive transition to high school. The program was tested in its original 6-session format and in a modified format (CSP-Plus), which added 2 sessions that included adolescents. Over 2 annual cohorts, 321 families were enrolled and randomly assigned to either the CSP, CSP-Plus, or minimal-contact control condition. Pretest, posttest, 1-year follow-up, and 2-year follow-up survey data on parenting as well as youth school bonding, social skills, and problem behaviors were collected from parents and youth (94% retention). Extending prior examinations of posttest outcomes, intent-to-treat regression analyses tested for intervention effects at the 2 follow-up assessments, and growth curve analyses examined experimental condition differences in yearly change across time. Separate exploratory tests of moderation by youth gender, youth conduct problems, and family economic hardship also were conducted. Out of 52 regression models predicting 1- and 2-year follow-up outcomes, only 2 out of 104 possible intervention effects were statistically significant. No statistically significant intervention effects were found in the growth curve analyses. Tests of moderation also showed few statistically significant effects. Because CSP already is in widespread use, findings have direct implications for practice. Specifically, findings suggest that the program may not be efficacious with parents of adolescents in a selective prevention context and may reveal the limits of brief, general parent training for achieving outcomes with parents of adolescents. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Daily potassium intake and sodium-to-potassium ratio in the reduction of blood pressure: a meta-analysis of randomized controlled trials.

PubMed

Binia, Aristea; Jaeger, Jonathan; Hu, Youyou; Singh, Anurag; Zimmermann, Diane

2015-08-01

To evaluate the efficacy of daily potassium intake on decreasing blood pressure in non-medicated normotensive or hypertensive patients, and to determine the relationship between potassium intake, sodium-to-potassium ratio and reduction in blood pressure. Mixed-effect meta-analyses and meta-regression models. Medline and the references of previous meta-analyses. Randomized controlled trials with potassium supplementation, with blood pressure as the primary outcome, in non-medicated patients. Fifteen randomized controlled trials of potassium supplementation in patients without antihypertensive medication were selected for the meta-analyses (917 patients). Potassium supplementation resulted in reduction of SBP by 4.7 mmHg [95% confidence interval (CI) 2.4-7.0] and DBP by 3.5 mmHg (95% CI 1.3-5.7) in all patients. The effect was found to be greater in hypertensive patients, with a reduction of SBP by 6.8 mmHg (95% CI 4.3-9.3) and DBP by 4.6 mmHg (95% CI 1.8-7.5). Meta-regression analysis showed that both increased daily potassium excretion and decreased sodium-to-potassium ratio were associated with blood pressure reduction (P < 0.05). Increased total daily potassium urinary excretion from 60 to 100 mmol/day and decrease of sodium-to-potassium ratio were shown to be necessary to explain the estimated effect. Potassium supplementation is associated with reduction of blood pressure in patients who are not on antihypertensive medication, and the effect is significant in hypertensive patients. The reduction in blood pressure significantly correlates with decreased daily urinary sodium-to-potassium ratio and increased urinary potassium. Patients with elevated blood pressure may benefit from increased potassium intake along with controlled or decreased sodium intake.

Point process analyses of variations in smoking rate by setting, mood, gender, and dependence

PubMed Central

Shiffman, Saul; Rathbun, Stephen L.

2010-01-01

The immediate emotional and situational antecedents of ad libitum smoking are still not well understood. We re-analyzed data from Ecological Momentary Assessment using novel point-process analyses, to assess how craving, mood, and social setting influence smoking rate, as well as assessing the moderating effects of gender and nicotine dependence. 304 smokers recorded craving, mood, and social setting using electronic diaries when smoking and at random nonsmoking times over 16 days of smoking. Point-process analysis, which makes use of the known random sampling scheme for momentary variables, examined main effects of setting and interactions with gender and dependence. Increased craving was associated with higher rates of smoking, particularly among women. Negative affect was not associated with smoking rate, even in interaction with arousal, but restlessness was associated with substantially higher smoking rates. Women's smoking tended to be less affected by negative affect. Nicotine dependence had little moderating effect on situational influences. Smoking rates were higher when smokers were alone or with others smoking, and smoking restrictions reduced smoking rates. However, the presence of others smoking undermined the effects of restrictions. The more sensitive point-process analyses confirmed earlier findings, including the surprising conclusion that negative affect by itself was not related to smoking rates. Contrary to hypothesis, men's and not women's smoking was influenced by negative affect. Both smoking restrictions and the presence of others who are not smoking suppress smoking, but others’ smoking undermines the effects of restrictions. Point-process analyses of EMA data can bring out even small influences on smoking rate. PMID:21480683

A mixture model for bovine abortion and foetal survival.

PubMed

Hanson, Timothy; Bedrick, Edward J; Johnson, Wesley O; Thurmond, Mark C

2003-05-30

The effect of spontaneous abortion on the dairy industry is substantial, costing the industry on the order of US dollars 200 million per year in California alone. We analyse data from a cohort study of nine dairy herds in Central California. A key feature of the analysis is the observation that only a relatively small proportion of cows will abort (around 10;15 per cent), so that it is inappropriate to analyse the time-to-abortion (TTA) data as if it were standard censored survival data, with cows that fail to abort by the end of the study treated as censored observations. We thus broaden the scope to consider the analysis of foetal lifetime distribution (FLD) data for the cows, with the dual goals of characterizing the effects of various risk factors on (i). the likelihood of abortion and, conditional on abortion status, on (ii). the risk of early versus late abortion. A single model is developed to accomplish both goals with two sets of specific herd effects modelled as random effects. Because multimodal foetal hazard functions are expected for the TTA data, both a parametric mixture model and a non-parametric model are developed. Furthermore, the two sets of analyses are linked because of anticipated dependence between the random herd effects. All modelling and inferences are accomplished using modern Bayesian methods. Copyright 2003 John Wiley & Sons, Ltd.

Garlic and Heart Disease.

PubMed

Varshney, Ravi; Budoff, Matthew J

2016-02-01

Thousands of studies have been published based on animal and human studies evaluating garlic's effects and safety. We reviewed the available literature investigating the effects of garlic supplements on hypertension, hypercholesterolemia, C-reactive protein (CRP), pulse wave velocity (PWV), and coronary artery calcium (CAC), as well as available data on side effects. We searched PubMed for all human studies using medical subject heading words through 30 May 2013 and assessed relevant review articles and original studies. Only double-blind, randomized, controlled trials and meta-analyses of double-blind, randomized, controlled trials were included. The review of articles and data extraction were performed by 2 independent authors, with any disagreements resolved by consensus. Garlic supplementation reduced blood pressure by 7-16 mm Hg (systolic) and 5-9 mm Hg (diastolic) (4 meta-analyses and 2 original studies). It reduced total cholesterol by 7.4-29.8 mg/dL (8 meta-analyses). The most consistent benefits were shown in studies that used aged garlic extract (AGE). A few small studies that used AGE also showed favorable effects on CAC, CRP, and PWV. Although garlic is generally safe, rare adverse reactions have been documented with limited causality established. We conclude that garlic supplementation has the potential for cardiovascular protection based on risk factor reduction (hypertension and total cholesterol) and surrogate markers (CRP, PWV, and CAC) of atherosclerosis. Larger studies are warranted to evaluate these effects further. © 2016 American Society for Nutrition.

Factors associated with differential response to online cognitive behavioural therapy.

PubMed

Button, Katherine S; Wiles, Nicola J; Lewis, Glyn; Peters, Tim J; Kessler, David

2012-05-01

Patients differ in their response to treatments. There is obvious clinical utility in establishing patient characteristics that are associated with differential treatment responses (i.e., are effect modifiers or moderators of treatment response). Factors that moderate response to cognitive behavioural therapy (CBT) remain unclear. This study investigates whether factors prognostic of general depression outcome generally are also moderators of response to online CBT in a sample of depressed patients recruited through U.K. general practices. Secondary analysis of a randomised controlled trial, internet-based psychotherapy for depression. A total of 297 patients referred from 55 U.K. general practices and suffering from depression were randomly allocated to receive either online CBT or waiting list control. Treatment effect was measured by comparing depression score at 4 months between randomization groups. Treatment effect modification was assessed using regression analyses focusing on interactions between treatment effect and putative moderator variables. Pretreatment severity and marital status moderated treatment response. More severe patients, and patients who were separated, widowed, or divorced, benefited most from the intervention. Weak evidence suggested that treatment effectiveness diminished with increasing recent adverse life events. No evidence was found to suggest that educational attainment, age, and history of depression-moderated treatment response. Secondary analyses of trials comparing two or more treatments allow factors that may moderate treatment response to be distinguished from more general prognostic indicators, although caution is needed in interpreting such exploratory analyses.

Analyzing social experiments as implemented: A reexamination of the evidence from the HighScope Perry Preschool Program

PubMed Central

Heckman, James; Moon, Seong Hyeok; Pinto, Rodrigo; Savelyev, Peter; Yavitz, Adam

2012-01-01

Social experiments are powerful sources of information about the effectiveness of interventions. In practice, initial randomization plans are almost always compromised. Multiple hypotheses are frequently tested. “Significant” effects are often reported with p-values that do not account for preliminary screening from a large candidate pool of possible effects. This paper develops tools for analyzing data from experiments as they are actually implemented. We apply these tools to analyze the influential HighScope Perry Preschool Program. The Perry program was a social experiment that provided preschool education and home visits to disadvantaged children during their preschool years. It was evaluated by the method of random assignment. Both treatments and controls have been followed from age 3 through age 40. Previous analyses of the Perry data assume that the planned randomization protocol was implemented. In fact, as in many social experiments, the intended randomization protocol was compromised. Accounting for compromised randomization, multiple-hypothesis testing, and small sample sizes, we find statistically significant and economically important program effects for both males and females. We also examine the representativeness of the Perry study. PMID:23255883

Simulation of wave propagation in three-dimensional random media

NASA Astrophysics Data System (ADS)

Coles, Wm. A.; Filice, J. P.; Frehlich, R. G.; Yadlowsky, M.

1995-04-01

Quantitative error analyses for the simulation of wave propagation in three-dimensional random media, when narrow angular scattering is assumed, are presented for plane-wave and spherical-wave geometry. This includes the errors that result from finite grid size, finite simulation dimensions, and the separation of the two-dimensional screens along the propagation direction. Simple error scalings are determined for power-law spectra of the random refractive indices of the media. The effects of a finite inner scale are also considered. The spatial spectra of the intensity errors are calculated and compared with the spatial spectra of

Novel image encryption algorithm based on multiple-parameter discrete fractional random transform

NASA Astrophysics Data System (ADS)

Zhou, Nanrun; Dong, Taiji; Wu, Jianhua

2010-08-01

A new method of digital image encryption is presented by utilizing a new multiple-parameter discrete fractional random transform. Image encryption and decryption are performed based on the index additivity and multiple parameters of the multiple-parameter fractional random transform. The plaintext and ciphertext are respectively in the spatial domain and in the fractional domain determined by the encryption keys. The proposed algorithm can resist statistic analyses effectively. The computer simulation results show that the proposed encryption algorithm is sensitive to the multiple keys, and that it has considerable robustness, noise immunity and security.

Peer Inclusion in Interventions for Children with ADHD: A Systematic Review and Meta-Analysis

PubMed Central

Vilaysack, Brandon; Doma, Kenji; Wilkes-Gillan, Sarah; Speyer, Renée

2018-01-01

Objective To assess the effectiveness of peer inclusion in interventions to improve the social functioning of children with ADHD. Methods We searched four electronic databases for randomized controlled trials and controlled quasi-experimental studies that investigated peer inclusion interventions alone or combined with pharmacological treatment. Data were collected from the included studies and methodologically assessed. Meta-analyses were conducted using a random-effects model. Results Seventeen studies met eligibility criteria. Studies investigated interventions consisting of peer involvement and peer proximity; no study included peer mediation. Most included studies had an unclear or high risk of bias regarding inadequate reporting of randomization, blinding, and control for confounders. Meta-analyses indicated improvements in pre-post measures of social functioning for participants in peer-inclusive treatment groups. Peer inclusion was advantageous compared to treatment as usual. The benefits of peer inclusion over other therapies or medication only could not be determined. Using parents as raters for outcome measurement significantly mediated the intervention effect. Conclusions The evidence to support or contest the efficacy of peer inclusion interventions for children with ADHD is lacking. Future studies need to reduce risks of bias, use appropriate sample sizes, and provide detailed results to investigate the efficacy of peer inclusion interventions for children with ADHD. PMID:29744363

Effect of motivational interviewing on rates of early childhood caries: a randomized trial.

PubMed

Harrison, Rosamund; Benton, Tonya; Everson-Stewart, Siobhan; Weinstein, Phil

2007-01-01

The purposes of this randomized controlled trial were to: (1) test motivational interviewing (MI) to prevent early childhood caries; and (2) use Poisson regression for data analysis. A total of 240 South Asian children 6 to 18 months old were enrolled and randomly assigned to either the MI or control condition. Children had a dental exam, and their mothers completed pretested instruments at baseline and 1 and 2 years postintervention. Other covariates that might explain outcomes over and above treatment differences were modeled using Poisson regression. Hazard ratios were produced. Analyses included all participants whenever possible. Poisson regression supported a protective effect of MI (hazard ratio [HR]=0.54 (95%CI=035-0.84)-that is, the M/ group had about a 46% lower rate of dmfs at 2 years than did control children. Similar treatment effect estimates were obtained from models that included, as alternative outcomes, ds, dms, and dmfs, including "white spot lesions." Exploratory analyses revealed that rates of dmfs were higher in children whose mothers had: (1) prechewed their food; (2) been raised in a rural environment; and (3) a higher family income (P<.05). A motivational interviewing-style intervention shows promise to promote preventive behaviors in mothers of young children at high risk for caries.

Efficacy of cognitive behavioral internet-based therapy in parents after the loss of a child during pregnancy: pilot data from a randomized controlled trial.

PubMed

Kersting, Anette; Kroker, Kristin; Schlicht, Sarah; Baust, Katja; Wagner, Birgit

2011-12-01

The loss of a child during pregnancy can be a traumatic event associated with long-lasting grief and psychological distress. This study examined the efficacy of an internet-based cognitive behavioral therapy program for mothers after pregnancy loss. In a randomized controlled trial with a waiting list control group, 83 participants who had lost a child during pregnancy were randomly allocated either to 5 weeks of internet therapy or to a 5-week waiting condition. Within a manualized cognitive behavioral treatment program, participants wrote ten essays on loss-specific topics. Posttraumatic stress, grief, and general psychopathology, especially depression, were assessed pretreatment, posttreatment, and at 3-month follow-up. Intention-to-treat analyses and completer analyses were performed. Relative to controls, participants in the treatment group showed significant improvements in posttraumatic stress, grief, depression, and overall mental health, but not in anxiety or somatization. Medium to large effect sizes were observed, and the improvement was maintained at 3-month follow-up. This internet-based cognitive behavioral therapy program represents an effective treatment approach with stable effects for women after pregnancy loss. Implementation of the program can thus help to improve the health care provision for mothers in this traumatic loss situation.

A Two-Step Approach for Analysis of Nonignorable Missing Outcomes in Longitudinal Regression: an Application to Upstate KIDS Study.

PubMed

Liu, Danping; Yeung, Edwina H; McLain, Alexander C; Xie, Yunlong; Buck Louis, Germaine M; Sundaram, Rajeshwari

2017-09-01

Imperfect follow-up in longitudinal studies commonly leads to missing outcome data that can potentially bias the inference when the missingness is nonignorable; that is, the propensity of missingness depends on missing values in the data. In the Upstate KIDS Study, we seek to determine if the missingness of child development outcomes is nonignorable, and how a simple model assuming ignorable missingness would compare with more complicated models for a nonignorable mechanism. To correct for nonignorable missingness, the shared random effects model (SREM) jointly models the outcome and the missing mechanism. However, the computational complexity and lack of software packages has limited its practical applications. This paper proposes a novel two-step approach to handle nonignorable missing outcomes in generalized linear mixed models. We first analyse the missing mechanism with a generalized linear mixed model and predict values of the random effects; then, the outcome model is fitted adjusting for the predicted random effects to account for heterogeneity in the missingness propensity. Extensive simulation studies suggest that the proposed method is a reliable approximation to SREM, with a much faster computation. The nonignorability of missing data in the Upstate KIDS Study is estimated to be mild to moderate, and the analyses using the two-step approach or SREM are similar to the model assuming ignorable missingness. The two-step approach is a computationally straightforward method that can be conducted as sensitivity analyses in longitudinal studies to examine violations to the ignorable missingness assumption and the implications relative to health outcomes. © 2017 John Wiley & Sons Ltd.

Bias and inference from misspecified mixed-effect models in stepped wedge trial analysis.

PubMed

Thompson, Jennifer A; Fielding, Katherine L; Davey, Calum; Aiken, Alexander M; Hargreaves, James R; Hayes, Richard J

2017-10-15

Many stepped wedge trials (SWTs) are analysed by using a mixed-effect model with a random intercept and fixed effects for the intervention and time periods (referred to here as the standard model). However, it is not known whether this model is robust to misspecification. We simulated SWTs with three groups of clusters and two time periods; one group received the intervention during the first period and two groups in the second period. We simulated period and intervention effects that were either common-to-all or varied-between clusters. Data were analysed with the standard model or with additional random effects for period effect or intervention effect. In a second simulation study, we explored the weight given to within-cluster comparisons by simulating a larger intervention effect in the group of the trial that experienced both the control and intervention conditions and applying the three analysis models described previously. Across 500 simulations, we computed bias and confidence interval coverage of the estimated intervention effect. We found up to 50% bias in intervention effect estimates when period or intervention effects varied between clusters and were treated as fixed effects in the analysis. All misspecified models showed undercoverage of 95% confidence intervals, particularly the standard model. A large weight was given to within-cluster comparisons in the standard model. In the SWTs simulated here, mixed-effect models were highly sensitive to departures from the model assumptions, which can be explained by the high dependence on within-cluster comparisons. Trialists should consider including a random effect for time period in their SWT analysis model. © 2017 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. © 2017 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.

Bias and inference from misspecified mixed‐effect models in stepped wedge trial analysis

PubMed Central

Fielding, Katherine L.; Davey, Calum; Aiken, Alexander M.; Hargreaves, James R.; Hayes, Richard J.

2017-01-01

Many stepped wedge trials (SWTs) are analysed by using a mixed‐effect model with a random intercept and fixed effects for the intervention and time periods (referred to here as the standard model). However, it is not known whether this model is robust to misspecification. We simulated SWTs with three groups of clusters and two time periods; one group received the intervention during the first period and two groups in the second period. We simulated period and intervention effects that were either common‐to‐all or varied‐between clusters. Data were analysed with the standard model or with additional random effects for period effect or intervention effect. In a second simulation study, we explored the weight given to within‐cluster comparisons by simulating a larger intervention effect in the group of the trial that experienced both the control and intervention conditions and applying the three analysis models described previously. Across 500 simulations, we computed bias and confidence interval coverage of the estimated intervention effect. We found up to 50% bias in intervention effect estimates when period or intervention effects varied between clusters and were treated as fixed effects in the analysis. All misspecified models showed undercoverage of 95% confidence intervals, particularly the standard model. A large weight was given to within‐cluster comparisons in the standard model. In the SWTs simulated here, mixed‐effect models were highly sensitive to departures from the model assumptions, which can be explained by the high dependence on within‐cluster comparisons. Trialists should consider including a random effect for time period in their SWT analysis model. © 2017 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. PMID:28556355

Effectiveness of a Web-Based Screening and Fully Automated Brief Motivational Intervention for Adolescent Substance Use: A Randomized Controlled Trial.

PubMed

Arnaud, Nicolas; Baldus, Christiane; Elgán, Tobias H; De Paepe, Nina; Tønnesen, Hanne; Csémy, Ladislav; Thomasius, Rainer

2016-05-24

Mid-to-late adolescence is a critical period for initiation of alcohol and drug problems, which can be reduced by targeted brief motivational interventions. Web-based brief interventions have advantages in terms of acceptability and accessibility and have shown significant reductions of substance use among college students. However, the evidence is sparse among adolescents with at-risk use of alcohol and other drugs. This study evaluated the effectiveness of a targeted and fully automated Web-based brief motivational intervention with no face-to-face components on substance use among adolescents screened for at-risk substance use in four European countries. In an open-access, purely Web-based randomized controlled trial, a convenience sample of adolescents aged 16-18 years from Sweden, Germany, Belgium, and the Czech Republic was recruited using online and offline methods and screened online for at-risk substance use using the CRAFFT (Car, Relax, Alone, Forget, Friends, Trouble) screening instrument. Participants were randomized to a single session brief motivational intervention group or an assessment-only control group but not blinded. Primary outcome was differences in past month drinking measured by a self-reported AUDIT-C-based index score for drinking frequency, quantity, and frequency of binge drinking with measures collected online at baseline and after 3 months. Secondary outcomes were the AUDIT-C-based separate drinking indicators, illegal drug use, and polydrug use. All outcome analyses were conducted with and without Expectation Maximization (EM) imputation of missing follow-up data. In total, 2673 adolescents were screened and 1449 (54.2%) participants were randomized to the intervention or control group. After 3 months, 211 adolescents (14.5%) provided follow-up data. Compared to the control group, results from linear mixed models revealed significant reductions in self-reported past-month drinking in favor of the intervention group in both the non-imputed (P=.010) and the EM-imputed sample (P=.022). Secondary analyses revealed a significant effect on drinking frequency (P=.037) and frequency of binge drinking (P=.044) in the non-imputation-based analyses and drinking quantity (P=.021) when missing data were imputed. Analyses for illegal drug use and polydrug use revealed no significant differences between the study groups (Ps>.05). Although the study is limited by a large drop-out, significant between-group effects for alcohol use indicate that targeted brief motivational intervention in a fully automated Web-based format can be effective to reduce drinking and lessen existing substance use service barriers for at-risk drinking European adolescents. International Standard Randomized Controlled Trial Registry: ISRCTN95538913; http://www.isrctn.com/ISRCTN95538913 (Archived by WebCite at http://www.webcitation.org/6XkuUEwBx).

Perspective: NutriGrade: A Scoring System to Assess and Judge the Meta-Evidence of Randomized Controlled Trials and Cohort Studies in Nutrition Research.

PubMed

Schwingshackl, Lukas; Knüppel, Sven; Schwedhelm, Carolina; Hoffmann, Georg; Missbach, Benjamin; Stelmach-Mardas, Marta; Dietrich, Stefan; Eichelmann, Fabian; Kontopantelis, Evangelos; Iqbal, Khalid; Aleksandrova, Krasimira; Lorkowski, Stefan; Leitzmann, Michael F; Kroke, Anja; Boeing, Heiner

2016-11-01

The objective of this study was to develop a scoring system (NutriGrade) to evaluate the quality of evidence of randomized controlled trial (RCT) and cohort study meta-analyses in nutrition research, building upon previous tools and expert recommendations. NutriGrade aims to assess the meta-evidence of an association or effect between different nutrition factors and outcomes, taking into account nutrition research-specific requirements not considered by other tools. In a pretest study, 6 randomly selected meta-analyses investigating diet-disease relations were evaluated with NutriGrade by 5 independent raters. After revision, NutriGrade was applied by the same raters to 30 randomly selected meta-analyses in the same thematic area. The reliability of ratings of NutriGrade items was calculated with the use of a multirater κ, and reliability of the total (summed scores) was calculated with the use of intraclass correlation coefficients (ICCs). The following categories for meta-evidence evaluation were established: high (8-10), moderate (6-7.99), low (4-5.99), and very low (0-3.99). The NutriGrade scoring system (maximum of 10 points) comprises the following items: 1) risk of bias, study quality, and study limitations, 2) precision, 3) heterogeneity, 4) directness, 5) publication bias, 6) funding bias, 7) study design, 8) effect size, and 9) dose-response. The NutriGrade score varied between 2.9 (very low meta-evidence) and 8.8 (high meta-evidence) for meta-analyses of RCTs, and it ranged between 3.1 and 8.8 for meta-analyses of cohort studies. The κ value of the ratings for each scoring item varied from 0.32 (95% CI: 0.22, 0.42) for risk of bias for cohort studies and 0.95 (95% CI: 0.91, 0.99) for study design, with a mean κ of 0.66 (95% CI: 0.53, 0.79). The ICC of the total score was 0.81 (95% CI: 0.69, 0.90). The NutriGrade scoring system showed good agreement and reliability. The initial findings regarding the performance of this newly established scoring system need further evaluation in independent analyses. © 2016 American Society for Nutrition.

Perspective: NutriGrade: A Scoring System to Assess and Judge the Meta-Evidence of Randomized Controlled Trials and Cohort Studies in Nutrition Research123

PubMed Central

Knüppel, Sven; Schwedhelm, Carolina; Hoffmann, Georg; Missbach, Benjamin; Stelmach-Mardas, Marta; Dietrich, Stefan; Eichelmann, Fabian; Kontopanteils, Evangelos; Iqbal, Khalid; Aleksandrova, Krasimira; Lorkowski, Stefan; Leitzmann, Michael F; Kroke, Anja; Boeing, Heiner

2016-01-01

The objective of this study was to develop a scoring system (NutriGrade) to evaluate the quality of evidence of randomized controlled trial (RCT) and cohort study meta-analyses in nutrition research, building upon previous tools and expert recommendations. NutriGrade aims to assess the meta-evidence of an association or effect between different nutrition factors and outcomes, taking into account nutrition research–specific requirements not considered by other tools. In a pretest study, 6 randomly selected meta-analyses investigating diet–disease relations were evaluated with NutriGrade by 5 independent raters. After revision, NutriGrade was applied by the same raters to 30 randomly selected meta-analyses in the same thematic area. The reliability of ratings of NutriGrade items was calculated with the use of a multirater κ, and reliability of the total (summed scores) was calculated with the use of intraclass correlation coefficients (ICCs). The following categories for meta-evidence evaluation were established: high (8–10), moderate (6–7.99), low (4–5.99), and very low (0–3.99). The NutriGrade scoring system (maximum of 10 points) comprises the following items: 1) risk of bias, study quality, and study limitations, 2) precision, 3) heterogeneity, 4) directness, 5) publication bias, 6) funding bias, 7) study design, 8) effect size, and 9) dose-response. The NutriGrade score varied between 2.9 (very low meta-evidence) and 8.8 (high meta-evidence) for meta-analyses of RCTs, and it ranged between 3.1 and 8.8 for meta-analyses of cohort studies. The κ value of the ratings for each scoring item varied from 0.32 (95% CI: 0.22, 0.42) for risk of bias for cohort studies and 0.95 (95% CI: 0.91, 0.99) for study design, with a mean κ of 0.66 (95% CI: 0.53, 0.79). The ICC of the total score was 0.81 (95% CI: 0.69, 0.90). The NutriGrade scoring system showed good agreement and reliability. The initial findings regarding the performance of this newly established scoring system need further evaluation in independent analyses. PMID:28140319

Effect of cinnamon on glucose control and lipid parameters.

PubMed

Baker, William L; Gutierrez-Williams, Gabriela; White, C Michael; Kluger, Jeffrey; Coleman, Craig I

2008-01-01

To perform a meta-analysis of randomized controlled trials of cinnamon to better characterize its impact on glucose and plasma lipids. A systematic literature search through July 2007 was conducted to identify randomized placebo-controlled trials of cinnamon that reported data on A1C, fasting blood glucose (FBG), or lipid parameters. The mean change in each study end point from baseline was treated as a continuous variable, and the weighted mean difference was calculated as the difference between the mean value in the treatment and control groups. A random-effects model was used. Five prospective randomized controlled trials (n = 282) were identified. Upon meta-analysis, the use of cinnamon did not significantly alter A1C, FBG, or lipid parameters. Subgroup and sensitivity analyses did not significantly change the results. Cinnamon does not appear to improve A1C, FBG, or lipid parameters in patients with type 1 or type 2 diabetes.

Protein Diet Restriction Slows Chronic Kidney Disease Progression in Non-Diabetic and in Type 1 Diabetic Patients, but Not in Type 2 Diabetic Patients: A Meta-Analysis of Randomized Controlled Trials Using Glomerular Filtration Rate as a Surrogate

PubMed Central

Rughooputh, Mahesh Shumsher; Zeng, Rui; Yao, Ying

2015-01-01

Background/ Objective Studies, including various meta-analyses, on the effect of Protein Diet Restriction on Glomerular Filtration Rate (GFR) in Chronic Kidney Disease (CKD) have reported conflicting results. In this paper, we have provided an update on the evidence available on this topic. We have investigated the reasons why the effect has been inconsistent across studies. We have also compared the effect on GFR in various subgroups including type 1 diabetics, type 2 diabetics and non-diabetics. Method We searched for Randomized Controlled Trials on this intervention from MEDLINE, EMBASE, and other information sources. The PRISMA guidelines, as well as recommended meta-analysis practices were followed in the selection process, analysis and reporting of our findings. The effect estimate used was the change in mean GFR. Heterogeneity across the considered studies was explored using both subgroup analyses and meta-regression. Quality assessment was done using the Cochrane risk of bias tool and sensitivity analyses. Results 15 randomized controlled trials, including 1965 subjects, were analyzed. The pooled effect size, as assessed using random-effects model, for all the 15 studies was -0.95 ml/min/1.73m2/year (95% CI: -1.79, -0.11), with a significant p value of 0.03. The combined effect estimate for the non-diabetic and type 1 diabetic studies was -1.50 ml/min/1.73m2/year (95% CI: -2.73, -0.26) with p value of 0.02. The effect estimate for the type 2 diabetic group was -0.17 ml/min/1.73m2/year (95% CI: -1.88, 1.55) with p value of 0.85. There was significant heterogeneity across the included studies (I2 = 74%, p value for Q < 0.0001), explained by major variations in the percentage of type 2 diabetic subjects, the number of subjects and overall compliance level to diet prescribed. Conclusion Our findings suggest that protein diet restriction slows chronic renal disease progression in non-diabetic and in type 1 diabetic patients, but not in type 2 diabetic patients. PMID:26710078

Incidence and effects of endemic populations of forest pests in young mixed-conifer forests of the Sierra Nevada

Treesearch

Carroll B. Williams; David L. Azuma; George T. Ferrell

1992-01-01

Approximately 3.200 trees in young mixed-conifer stands were examined for pest activity and human-caused or mechanical injuries, and approximately 25 percent of these trees were randomly selected for stem analyses. The examination of trees felled for stem analyses showed that 409 (47 percent) were free of pests and 466 (53 percent) had one or more pest categories....

Valid randomization-based p-values for partially post hoc subgroup analyses.

PubMed

Lee, Joseph J; Rubin, Donald B

2015-10-30

By 'partially post-hoc' subgroup analyses, we mean analyses that compare existing data from a randomized experiment-from which a subgroup specification is derived-to new, subgroup-only experimental data. We describe a motivating example in which partially post hoc subgroup analyses instigated statistical debate about a medical device's efficacy. We clarify the source of such analyses' invalidity and then propose a randomization-based approach for generating valid posterior predictive p-values for such partially post hoc subgroups. Lastly, we investigate the approach's operating characteristics in a simple illustrative setting through a series of simulations, showing that it can have desirable properties under both null and alternative hypotheses. Copyright © 2015 John Wiley & Sons, Ltd.

Improving Adherence to Smoking Cessation Treatment: Smoking Outcomes in a Web-based Randomized Trial.

PubMed

Graham, Amanda L; Papandonatos, George D; Cha, Sarah; Erar, Bahar; Amato, Michael S

2018-03-15

Partial adherence in Internet smoking cessation interventions presents treatment and evaluation challenges. Increasing adherence may improve outcomes. To present smoking outcomes from an Internet randomized trial of two strategies to encourage adherence to tobacco dependence treatment components: (i) a social network (SN) strategy to integrate smokers into an online community and (ii) free nicotine replacement therapy (NRT). In addition to intent-to-treat analyses, we used novel statistical methods to distinguish the impact of treatment assignment from treatment utilization. A total of 5,290 current smokers on a cessation website (WEB) were randomized to WEB, WEB + SN, WEB + NRT, or WEB + SN + NRT. The main outcome was 30-day point prevalence abstinence at 3 and 9 months post-randomization. Adherence measures included self-reported medication use (meds), and website metrics of skills training (sk) and community use (comm). Inverse Probability of Retention Weighting and Inverse Probability of Treatment Weighting jointly addressed dropout and treatment selection. Propensity weights were used to calculate Average Treatment effects on the Treated. Treatment assignment analyses showed no effects on abstinence for either adherence strategy. Abstinence rates were 25.7%-32.2% among participants that used all three treatment components (sk+comm +meds).Treatment utilization analyses revealed that among such participants, sk+comm+meds yielded large percentage point increases in 3-month abstinence rates over sk alone across arms: WEB = 20.6 (95% CI = 10.8, 30.4), WEB + SN = 19.2 (95% CI = 11.1, 27.3), WEB + NRT = 13.1 (95% CI = 4.1, 22.0), and WEB + SN + NRT = 20.0 (95% CI = 12.2, 27.7). Novel propensity weighting approaches can serve as a model for establishing efficacy of Internet interventions and yield important insights about mechanisms. NCT01544153.

Effects of exercise on depressive symptoms in adults with arthritis and other rheumatic disease: a systematic review of meta-analyses

PubMed Central

2014-01-01

Background Depression is a major public health problem among adults with arthritis and other rheumatic disease. The purpose of this study was to conduct a systematic review of previous meta-analyses addressing the effects of exercise (aerobic, strength or both) on depressive symptoms in adults with osteoarthritis, rheumatoid arthritis, fibromyalgia and systemic lupus erythematous. Methods Previous meta-analyses of randomized controlled trials were included by searching nine electronic databases and cross-referencing. Methodological quality was assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) Instrument. Random-effects models that included the standardized mean difference (SMD) and 95% confidence intervals (CIs) were reported. The alpha value for statistical significance was set at p ≤ 0.05. The U3 index, number needed to treat (NNT) and number of US people who could benefit were also calculated. Results Of the 95 citations initially identified, two aggregate data meta-analyses representing 6 and 19 effect sizes in as many as 870 fibromyalgia participants were included. Methodological quality was 91% and 82%, respectively. Exercise minus control group reductions in depressive symptoms were found for both meta-analyses (SMD, -0.61, 95% CI, -0.99 to -0.23, p = 0.002; SMD, -0.32, 95% CI, -0.53 to -0.12, p = 0.002). Percentile improvements (U3) were equivalent to 22.9 and 12.6. The number needed to treat was 6 and 9 with an estimated 0.83 and 0.56 million US people with fibromyalgia potentially benefitting. Conclusions Exercise improves depressive symptoms in adults with fibromyalgia. However, a need exists for additional meta-analytic work on this topic. PMID:24708605

Avoiding Boundary Estimates in Hierarchical Linear Models through Weakly Informative Priors

ERIC Educational Resources Information Center

Chung, Yeojin; Rabe-Hesketh, Sophia; Gelman, Andrew; Dorie, Vincent; Liu, Jinchen

2012-01-01

Hierarchical or multilevel linear models are widely used for longitudinal or cross-sectional data on students nested in classes and schools, and are particularly important for estimating treatment effects in cluster-randomized trials, multi-site trials, and meta-analyses. The models can allow for variation in treatment effects, as well as…

Distributional Analysis in Educational Evaluation: A Case Study from the New York City Voucher Program

ERIC Educational Resources Information Center

Bitler, Marianne; Domina, Thurston; Penner, Emily; Hoynes, Hilary

2015-01-01

We use quantile treatment effects estimation to examine the consequences of the random-assignment New York City School Choice Scholarship Program across the distribution of student achievement. Our analyses suggest that the program had negligible and statistically insignificant effects across the skill distribution. In addition to contributing to…

Baseline adjustments for binary data in repeated cross-sectional cluster randomized trials.

PubMed

Nixon, R M; Thompson, S G

2003-09-15

Analysis of covariance models, which adjust for a baseline covariate, are often used to compare treatment groups in a controlled trial in which individuals are randomized. Such analysis adjusts for any baseline imbalance and usually increases the precision of the treatment effect estimate. We assess the value of such adjustments in the context of a cluster randomized trial with repeated cross-sectional design and a binary outcome. In such a design, a new sample of individuals is taken from the clusters at each measurement occasion, so that baseline adjustment has to be at the cluster level. Logistic regression models are used to analyse the data, with cluster level random effects to allow for different outcome probabilities in each cluster. We compare the estimated treatment effect and its precision in models that incorporate a covariate measuring the cluster level probabilities at baseline and those that do not. In two data sets, taken from a cluster randomized trial in the treatment of menorrhagia, the value of baseline adjustment is only evident when the number of subjects per cluster is large. We assess the generalizability of these findings by undertaking a simulation study, and find that increased precision of the treatment effect requires both large cluster sizes and substantial heterogeneity between clusters at baseline, but baseline imbalance arising by chance in a randomized study can always be effectively adjusted for. Copyright 2003 John Wiley & Sons, Ltd.

Non-invasive brain stimulation to investigate language production in healthy speakers: A meta-analysis.

PubMed

Klaus, Jana; Schutter, Dennis J L G

2018-06-01

Non-invasive brain stimulation (NIBS) has become a common method to study the interrelations between the brain and language functioning. This meta-analysis examined the efficacy of transcranial magnetic stimulation (TMS) and direct current stimulation (tDCS) in the study of language production in healthy volunteers. Forty-five effect sizes from 30 studies which investigated the effects of NIBS on picture naming or verbal fluency in healthy participants were meta-analysed. Further sub-analyses investigated potential influences of stimulation type, control, target site, task, online vs. offline application, and current density of the target electrode. Random effects modelling showed a small, but reliable effect of NIBS on language production. Subsequent analyses indicated larger weighted mean effect sizes for TMS as compared to tDCS studies. No statistical differences for the other sub-analyses were observed. We conclude that NIBS is a useful method for neuroscientific studies on language production in healthy volunteers. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Bias from historical control groups used in orthodontic research: a meta-epidemiological study.

PubMed

Papageorgiou, Spyridon N; Koretsi, Vasiliki; Jäger, Andreas

2017-02-01

The validity of meta-analysis is dependent upon the quality of included studies. Here, we investigated whether the design of untreated control groups (i.e. source and timing of data collection) influences the results of clinical trials in orthodontic research. This meta-epidemiological study used unrestricted literature searching for meta-analyses in orthodontics including clinical trials with untreated control groups. Differences in standardized mean differences (ΔSMD) and their 95% confidence intervals (CIs) were calculated according to the untreated control group through multivariable random-effects meta-regression controlling for nature of the interventional group and study sample size. Effects were pooled with random-effects synthesis, followed by mixed-effect subgroup and sensitivity analyses. Studies with historical control groups reported deflated treatment effects compared to studies with concurrent control groups (13 meta-analyses; ΔSMD = -0.31; 95% CI = -0.53, -0.10; P = 0.004). Significant differences were found according to the type of historical control group (based either on growth study or clinical archive; 11 meta-analyses; ΔSMD = 0.40; 95% CI = 0.21, 0.59; P < 0.001). The use of historical control groups in orthodontic clinical research was associated with deflation of treatment effects, which was independent from whether the interventional group was prospective or retrospective and from the study's sample size. Caution is warranted when interpreting clinical studies with historical untreated control groups or when interpreting systematic reviews that include such studies. PROSPERO (CRD42015024179). None. © The Author 2016. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Binaural comodulation masking release: Effects of masker interaural correlation

PubMed Central

Hall, Joseph W.; Buss, Emily; Grose, John H.

2007-01-01

Binaural detection was examined for a signal presented in a narrow band of noise centered on the on-signal masking band (OSB) or in the presence of flanking noise bands that were random or comodulated with respect to the OSB. The noise had an interaural correlation of 1.0 (No), 0.99 or 0.95. In No noise, random flanking bands worsened Sπ detection and comodulated bands improved Sπ detection for some listeners but had no effect for other listeners. For the 0.99 or 0.95 interaural correlation conditions, random flanking bands were less detrimental to Sπ detection and comodulated flanking bands improved Sπ detection for all listeners. Analyses based on signal detection theory indicated that the improvement in Sπ thresholds obtained with comodulated bands was not compatible with an optimal combination of monaural and binaural cues or to across-frequency analyses of dynamic interaural phase differences. Two accounts consistent with the improvement in Sπ thresholds in comodulated noise were (1) envelope information carried by the flanking bands improves the weighting of binaural cues associated with the signal; (2) the auditory system is sensitive to across-frequency differences in ongoing interaural correlation. PMID:17225415

Design of trials for interrupting the transmission of endemic pathogens.

PubMed

Silkey, Mariabeth; Homan, Tobias; Maire, Nicolas; Hiscox, Alexandra; Mukabana, Richard; Takken, Willem; Smith, Thomas A

2016-06-06

Many interventions against infectious diseases have geographically diffuse effects. This leads to contamination between arms in cluster-randomized trials (CRTs). Pathogen elimination is the goal of many intervention programs against infectious agents, but contamination means that standard CRT designs and analyses do not provide inferences about the potential of interventions to interrupt pathogen transmission at maximum scale-up. A generic model of disease transmission was used to simulate infections in stepped wedge cluster-randomized trials (SWCRTs) of a transmission-reducing intervention, where the intervention has spatially diffuse effects. Simulations of such trials were then used to examine the potential of such designs for providing generalizable causal inferences about the impact of such interventions, including measurements of the contamination effects. The simulations were applied to the geography of Rusinga Island, Lake Victoria, Kenya, the site of the SolarMal trial on the use of odor-baited mosquito traps to eliminate Plasmodium falciparum malaria. These were used to compare variants in the proposed SWCRT designs for the SolarMal trial. Measures of contamination effects were found that could be assessed in the simulated trials. Inspired by analyses of trials of insecticide-treated nets against malaria when applied to the geography of the SolarMal trial, these measures were found to be robust to different variants of SWCRT design. Analyses of the likely extent of contamination effects supported the choice of cluster size for the trial. The SWCRT is an appropriate design for trials that assess the feasibility of local elimination of a pathogen. The effects of incomplete coverage can be estimated by analyzing the extent of contamination between arms in such trials, and the estimates also support inferences about causality. The SolarMal example illustrates how generic transmission models incorporating spatial smoothing can be used to simulate such trials for a power calculation and optimization of cluster size and randomization strategies. The approach is applicable to a range of infectious diseases transmitted via environmental reservoirs or via arthropod vectors.

The Effects of Cognitive Therapy Versus ‘Treatment as Usual’ in Patients with Major Depressive Disorder

PubMed Central

Jakobsen, Janus Christian; Lindschou Hansen, Jane; Storebø, Ole Jakob; Simonsen, Erik; Gluud, Christian

2011-01-01

Background Major depressive disorder afflicts an estimated 17% of individuals during their lifetimes at tremendous suffering and costs. Cognitive therapy may be an effective treatment option for major depressive disorder, but the effects have only had limited assessment in systematic reviews. Methods/Principal Findings Cochrane systematic review methodology, with meta-analyses and trial sequential analyses of randomized trials, are comparing the effects of cognitive therapy versus ‘treatment as usual’ for major depressive disorder. To be included the participants had to be older than 17 years with a primary diagnosis of major depressive disorder. Altogether, we included eight trials randomizing a total of 719 participants. All eight trials had high risk of bias. Four trials reported data on the 17-item Hamilton Rating Scale for Depression and four trials reported data on the Beck Depression Inventory. Meta-analysis on the data from the Hamilton Rating Scale for Depression showed that cognitive therapy compared with ‘treatment as usual’ significantly reduced depressive symptoms (mean difference −2.15 (95% confidence interval −3.70 to −0.60; P<0.007, no heterogeneity)). However, meta-analysis with both fixed-effect and random-effects model on the data from the Beck Depression Inventory (mean difference with both models −1.57 (95% CL −4.30 to 1.16; P = 0.26, I2 = 0) could not confirm the Hamilton Rating Scale for Depression results. Furthermore, trial sequential analysis on both the data from Hamilton Rating Scale for Depression and Becks Depression Inventory showed that insufficient data have been obtained. Discussion Cognitive therapy might not be an effective treatment for major depressive disorder compared with ‘treatment as usual’. The possible treatment effect measured on the Hamilton Rating Scale for Depression is relatively small. More randomized trials with low risk of bias, increased sample sizes, and broader more clinically relevant outcomes are needed. PMID:21829664

Grey literature in meta-analyses of randomized trials of health care interventions.

PubMed

Hopewell, S; McDonald, S; Clarke, M; Egger, M

2007-04-18

The inclusion of grey literature (i.e. literature that has not been formally published) in systematic reviews may help to overcome some of the problems of publication bias, which can arise due to the selective availability of data. To review systematically research studies, which have investigated the impact of grey literature in meta-analyses of randomized trials of health care interventions. We searched the Cochrane Methodology Register (The Cochrane Library Issue 3, 2005), MEDLINE (1966 to 20 May 2005), the Science Citation Index (June 2005) and contacted researchers who may have carried out relevant studies. A study was considered eligible for this review if it compared the effect of the inclusion and exclusion of grey literature on the results of a cohort of meta-analyses of randomized trials. Data were extracted from each report independently by two reviewers. The main outcome measure was an estimate of the impact of trials from the grey literature on the pooled effect estimates of the meta-analyses. Information was also collected on the area of health care, the number of meta-analyses, the number of trials, the number of trial participants, the year of publication of the trials, the language and country of publication of the trials, the number and type of grey and published literature, and methodological quality. Five studies met the inclusion criteria. All five studies showed that published trials showed an overall greater treatment effect than grey trials. This difference was statistically significant in one of the five studies. Data could be combined for three of the five studies. This showed that, on average, published trials showed a 9% greater treatment effect than grey trials (ratio of odds ratios for grey versus published trials 1.09; 95% CI 1.03-1.16). Overall there were more published trials included in the meta-analyses than grey trials (median 224 (IQR 108-365) versus 45(IQR 40-102)). Published trials had more participants on average. The most common types of grey literature were abstracts (55%) and unpublished data (30%). There is limited evidence to show whether grey trials are of poorer methodological quality than published trials. This review shows that published trials tend to be larger and show an overall greater treatment effect than grey trials. This has important implications for reviewers who need to ensure they identify grey trials, in order to minimise the risk of introducing bias into their review.

Pragmatically Applied Cervical and Thoracic Nonthrust Manipulation Versus Thrust Manipulation for Patients With Mechanical Neck Pain: A Multicenter Randomized Clinical Trial.

PubMed

Griswold, David; Learman, Ken; Kolber, Morey J; O'Halloran, Bryan; Cleland, Joshua A

2018-03-01

Study Design Randomized clinical trial. Background The comparative effectiveness between nonthrust manipulation (NTM) and thrust manipulation (TM) for mechanical neck pain has been investigated, with inconsistent results. Objective To compare the clinical effectiveness of concordant cervical and thoracic NTM and TM for patients with mechanical neck pain. Methods The Neck Disability Index (NDI) was the primary outcome. Secondary outcomes included the Patient-Specific Functional Scale (PSFS), numeric pain-rating scale (NPRS), deep cervical flexion endurance (DCF), global rating of change (GROC), number of visits, and duration of care. The covariate was clinical equipoise for intervention. Outcomes were collected at baseline, visit 2, and discharge. Patients were randomly assigned to receive either NTM or TM directed at the cervical and thoracic spines. Techniques and dosages were selected pragmatically and applied to the most symptomatic level. Two-way mixed-model analyses of covariance were used to assess clinical outcomes at 3 time points. Analyses of covariance were used to assess between-group differences for the GROC, number of visits, and duration of care at discharge. Results One hundred three patients were included in the analyses (NTM, n = 55 and TM, n = 48). The between-group analyses revealed no differences in outcomes on the NDI (P = .67), PSFS (P = .26), NPRS (P = .25), DCF (P = .98), GROC (P = .77), number of visits (P = .21), and duration of care (P = .61) for patients with mechanical neck pain who received either NTM or TM. Conclusion NTM and TM produce equivalent outcomes for patients with mechanical neck pain. The trial was registered with ClinicalTrials.gov (NCT02619500). Level of Evidence Therapy, level 1b. J Orthop Sports Phys Ther 2018;48(3):137-145. Epub 6 Feb 2018. doi:10.2519/jospt.2018.7738.

Recruitment techniques for alcohol pharmacotherapy clinical trials: A cost-benefit analysis.

PubMed

Tompkins, D Andrew; Sides, Jessica A; Harrison, Joseph A; Strain, Eric C

2015-12-01

Alcohol use disorders (AUDs) represent a large public health burden with relatively few efficacious pharmacotherapies. Randomized controlled trials (RCTs) for new AUD therapies can be hampered by ineffective recruitment, leading to increased trial costs. The current analyses examined the effectiveness of recruitment efforts during two consecutive outpatient RCTs of novel AUD pharmacotherapies conducted between 2009 and 2012. During an initial phone screen, participants identified an ad source for learning about the study. Qualified persons were then scheduled for in-person screens. The present analyses examined demographic differences amongst the eight ad sources utilized. Recruitment effectiveness was determined by dividing the number of persons meeting criteria for an in-person screen by the total number of callers from each ad source. Cost-effectiveness was determined by dividing total ad source cost by number of screens, participants randomized, and completers. 1,813 calls resulted in 1,005 completed phone screens. The most common ad source was TV (34%), followed by print (29%), word-of-mouth (11%), flyer (8%), internet (5%), radio (5%), bus ad (2%), and billboard (1%). Participants reporting bus ads (46%), billboard (44%), or print ads (34%) were significantly more likely than the other sources to meet criteria to be scheduled for in-person screens. The most cost-effective ad source was print ($2,506 per completer), while bus ad was the least cost-effective ($13,376 per completer). Recruitment in AUD RCTs can be successful using diverse advertising methods. The present analyses favored use of print ads as most cost-effective.

The Baltimore Experience Corps Trial: Enhancing Generativity via Intergenerational Activity Engagement in Later Life

PubMed Central

Tanner, Elizabeth K.; Fried, Linda P.; Carlson, Michelle C.; Xue, Qian-Li; Parisi, Jeanine M.; Rebok, George W.; Yarnell, Lisa M.; Seeman, Teresa E.

2016-01-01

Objectives: Being and feeling generative, defined as exhibiting concern and behavior to benefit others, is an important developmental goal of midlife and beyond. Although a growing body of evidence suggests mental and physical health benefits of feeling generative in later life, little information exists as to the modifiability of generativity perceptions. The present study examines whether participation in the intergenerational civic engagement program, Experience Corps (EC), benefits older adults’ self-perceptions of generativity. Method: Levels of generativity were compared in older adults randomized to serve as EC volunteers or controls (usual volunteer opportunities) in the Baltimore Experience Corps Trial at 4-, 12-, and 24-month evaluation points over the 2-year trial. Analyses utilized intention-to-treat and complier average causal effects (CACE) analyses which incorporate degree of intervention exposure in analytic models. Results: Participants randomized to the EC group had significantly higher levels of generative desire and perceptions of generative achievement than controls at each follow-up point; CACE analyses indicate a dose–response effect with a greater magnitude of intervention effect with greater exposure to the EC program. Discussion: Results provide the first-ever, large-scale experimental demonstration that participation in an intergenerational civic engagement program can positively alter self-perceptions of generativity in older adulthood. PMID:25721053

'Scared Straight' and other juvenile awareness programs for preventing juvenile delinquency.

PubMed

Petrosino, Anthony; Turpin-Petrosino, Carolyn; Hollis-Peel, Meghan E; Lavenberg, Julia G

2013-04-30

'Scared Straight' and other similar programs involve organized visits to prison by juvenile delinquents or children at risk for criminal behavior. Programs are designed to deter participants from future offending through first hand observation of prison life and interaction with adult inmates. These programs remain in use despite research questioning their effectiveness. This is an update of a 2002 review. To assess the effects of programs comprising organized visits to prisons by juvenile delinquents (officially adjudicated, that is, convicted by a juvenile court) or pre-delinquents (children in trouble but not officially adjudicated as delinquents), aimed at deterring them from delinquency. To update this review, we searched 22 electronic databases, including CENTRAL, MEDLINE, PsycINFO, and Criminal Justice Abstracts, in December 2011. In addition, we searched clinical trials registries, consulted experts, conducted Google Scholar searches,and followed up on all relevant citations. We included studies that tested programs involving the organized visits of delinquents or children at risk for delinquency to penal institutions such as prisons or re formatives. Studies that had overlapping samples of juvenile and young adults (for example, ages 14 to 20 years) were included. We only considered studies that assigned participants to conditions randomly or quasi-randomly (that is,by odd/even assignment to conditions). Each study had to have a no-treatment control condition and at least one outcome measure of 'post-visit' criminal behavior. The search methods for the original review generated 487 citations, most of which had abstracts. The lead review author screened these citations, determining that 30 were evaluation reports. Two review authors independently examined these citations and agreed that 11 were potential randomized trials. All reports were obtained. Upon inspection of the full-text reports, two review authors independently agreed to exclude two studies, resulting in nine randomized trials. The lead review author extracted data from each of the nine study reports using a specially designed instrument. In cases in which outcome information was missing from the original reports, we made attempts via correspondence to retrieve the data for the analysis from the original investigators. Outcome data were independently checked by a second review author (CTP).In this review, we report the results of each of the nine trials narratively.We conducted two meta-analyses of seven studies that provided post intervention offending rates using official data. Information from other sources (for example, self-report) was either missing from some studies or critical information was omitted (for example, standard deviations).We examined the immediate post-treatment effects(that is, 'first-effects') by computing odds ratios (OR) for data on proportions of each group re offending, and assumed both fixed-effect and random-effects models in our analyses. We have included nine studies in this review. All were part of the original systematic review; no new trials meeting eligibility criteria were identified through our updated searches. The studies were conducted in eight different states of the USA, during the years 1967 to 1992. Nearly 1000 (946) juveniles or young adults of different races participated, almost all males. The average age of the participants in each study ranged from 15 to 17 years.Meta-analyses of seven studies show the intervention to be more harmful than doing nothing. The OR (fixed-effect) for effects on first post-treatment effect on officially measured criminal behavior indicated a negative program effect (OR 1.68, 95% confidence interval (CI) 1.20 to 2.36) and nearly identical regardless of the meta-analytic strategy (random-effectsOR 1.72, 95%CI 1.13 to 2.62).Sensitivity analyses (random-effects) showed the findings were robust even when removing one study with an inadequate randomization strategy (OR 1.47, 95% CI 1.03 to 2.11), or when removing one study with high attrition (OR 1.96, 95% CI 1.25 to 3.08), or both(OR 1.68, 95% CI 1.10 to 2.58). We conclude that programs such as 'cared Straight' increase delinquency relative to doing nothing at all to similar youths. Given these results, we cannot recommend this program as a crime prevention strategy. Agencies that permit such programs, therefore, must rigorously evaluate them, to ensure that they do not cause more harm than good to the very citizens they pledge to protect.

Family-focused preventive interventions: evaluating parental risk moderation of substance use trajectories.

PubMed

Guyll, Max; Spoth, Richard L; Chao, Wei; Wickrama, K A S; Russell, Daniel

2004-06-01

Four years of longitudinal data from 373 families participating in a randomized intervention-control clinical trial were used to examine whether intervention effects on adolescent alcohol and tobacco use trajectories were moderated by family risk, as defined by parental social emotional maladjustment. Consistent with earlier outcome evaluations based on analyses of covariance, analyses confirmed that both the Preparing for the Drug Free Years program and the Iowa Strengthening Families Program favorably influenced alcohol use index trajectories across the time frame of the study; only the latter program, however, evidenced positive effects on a tobacco use index. Concerning the primary research question, analyses provided no support for family risk moderation of any intervention effect. Findings indicate the feasibility of developing universal preventive interventions that offer comparable benefits to all families.

The Efficacy of a Universal School-Based Prevention Program for Eating Disorders among German Adolescents: Results from a Randomized-Controlled Trial.

PubMed

Warschburger, Petra; Zitzmann, Jana

2018-06-01

Disordered eating is highly prevalent during adolescence and has a detrimental effect on further development. Effective prevention programs are needed to prevent unhealthy developmental trajectories. This study evaluated the efficacy of the POPS-program (POtsdam Prevention at Schools), a universal school-based eating disorder prevention program for adolescents. In a cluster-randomized design, we compared the intervention group receiving the prevention program to a waiting control group. Outcomes included indicators of disordered eating and relevant risk factors for eating disorders (body dissatisfaction, internalization of the thin ideal, perceived media pressure, perfectionism, emotional element of exercise, social comparison, and perceived teasing). Questionnaires were administered at the start of the intervention, 3 and 12 months post intervention. At baseline, 1112 adolescents aged 10 to 16 years participated (49% girls; 51% intervention group). Intention-to-treat analyses with the complete data set and per-protocol analyses as a completer analysis were performed. The intervention group showed a more favorable course compared to the control group regarding all observed risk factors for eating disorders except for perceived teasing. Effect sizes were small but comparable to other primary prevention programs. At 1-year follow-up, a small but significant effect on disordered eating was observed. Results of the per-protocol analyses were mostly confirmed by the intention-to-treat analyses. Results were promising for both genders although girls benefited more regarding disordered eating and internalization of the thin ideal. Further studies are warranted examining successful program elements and whether gender-specific programs are needed.

A systematic appraisal of allegiance effect in randomized controlled trials of psychotherapy.

PubMed

Dragioti, Elena; Dimoliatis, Ioannis; Fountoulakis, Konstantinos N; Evangelou, Evangelos

2015-01-01

Experimenter's allegiance (EA) refers to a personal confidence of the superiority of a specific psychotherapy treatment. This factor has been linked with larger treatment effects in favor of the preferred treatment. However, various studies have displayed contradictory results between EA and the pattern of treatment effects. Using a systematic approach followed by meta-analysis, we aimed to evaluate the impact of an allegiance effect on the results of psychotherapeutic studies. We considered the meta-analyses of randomized controlled trials (RCTs) of different types of psychotherapies in the Cochrane Database of Systematic Reviews. Eligible articles included meta-analyses of RCTs with at least one study showing evidence of EA (i.e., allegiant study). Effect sizes in allegiant RCTs were compared with non-allegiant using random and fixed models and a summary relative odds ratio (ROR) were calculated. Heterogeneity was quantified with the I (2) metric. A total of 30 meta-analyses including 240 RCTs were analyzed. The summary ROR was 1.31 [(95 % confidence interval (CI: 1.03-1.66) P = 0.30, I (2) = 53 %] indicating larger effects when allegiance exists. The impact of allegiance did not differ significantly (P > 0.05) when we compared psychiatric versus medical outcomes. Allegiance effect was significant for all forms of psychotherapy except for cognitive behavioral therapy. Moreover, the impact of allegiance was significant only when the treatment integrity of delivered psychotherapy was not assessed. Allegiance effect was even stronger where the experimenter was also both the developer of the preferred treatment and supervised or trained the therapists. No significant differences were found between allegiant and non-allegiant studies in terms of overall quality of studies. Experimenter's allegiance influences the effect sizes of psychotherapy RCTs and can be considered non-financial conflict of interest introducing a form of optimism bias, especially since blinding is problematic in this kind of research. A clear reporting of EA in every single study should be given an opportunity to investigators of minimizing its overestimation effects.

Massage therapy for fibromyalgia: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Li, Yan-hui; Wang, Feng-yun; Feng, Chun-qing; Yang, Xia-feng; Sun, Yi-hua

2014-01-01

Although some studies evaluated the effectiveness of massage therapy for fibromyalgia (FM), the role of massage therapy in the management of FM remained controversial. The purpose of this systematic review is to evaluate the evidence of massage therapy for patients with FM. Electronic databases (up to June 2013) were searched to identify relevant studies. The main outcome measures were pain, anxiety, depression, and sleep disturbance. Two reviewers independently abstracted data and appraised risk of bias. The risk of bias of eligible studies was assessed based on Cochrane tools. Standardised mean difference (SMD) and 95% confidence intervals (CI) were calculated by more conservative random-effects model. And heterogeneity was assessed based on the I(2) statistic. Nine randomized controlled trials involving 404 patients met the inclusion criteria. The meta-analyses showed that massage therapy with duration ≥ 5 weeks significantly improved pain (SMD, 0.62; 95% CI 0.05 to 1.20; p = 0.03), anxiety (SMD, 0.44; 95% CI 0.09 to 0.78; p = 0.01), and depression (SMD, 0.49; 95% CI 0.15 to 0.84; p = 0.005) in patients with FM, but not on sleep disturbance (SMD, 0.19; 95% CI -0.38 to 0.75; p = 0.52). Massage therapy with duration ≥ 5 weeks had beneficial immediate effects on improving pain, anxiety, and depression in patients with FM. Massage therapy should be one of the viable complementary and alternative treatments for FM. However, given fewer eligible studies in subgroup meta-analyses and no evidence on follow-up effects, large-scale randomized controlled trials with long follow-up are warrant to confirm the current findings.

Do observational studies using propensity score methods agree with randomized trials? A systematic comparison of studies on acute coronary syndromes

PubMed Central

Dahabreh, Issa J.; Sheldrick, Radley C.; Paulus, Jessica K.; Chung, Mei; Varvarigou, Vasileia; Jafri, Haseeb; Rassen, Jeremy A.; Trikalinos, Thomas A.; Kitsios, Georgios D.

2012-01-01

Aims Randomized controlled trials (RCTs) are the gold standard for assessing the efficacy of therapeutic interventions because randomization protects from biases inherent in observational studies. Propensity score (PS) methods, proposed as a potential solution to confounding of the treatment–outcome association, are widely used in observational studies of therapeutic interventions for acute coronary syndromes (ACS). We aimed to systematically assess agreement between observational studies using PS methods and RCTs on therapeutic interventions for ACS. Methods and results We searched for observational studies of interventions for ACS that used PS methods to estimate treatment effects on short- or long-term mortality. Using a standardized algorithm, we matched observational studies to RCTs based on patients’ characteristics, interventions, and outcomes (‘topics’), and we compared estimates of treatment effect between the two designs. When multiple observational studies or RCTs were identified for the same topic, we performed a meta-analysis and used the summary relative risk for comparisons. We matched 21 observational studies investigating 17 distinct clinical topics to 63 RCTs (median = 3 RCTs per observational study) for short-term (7 topics) and long-term (10 topics) mortality. Estimates from PS analyses differed statistically significantly from randomized evidence in two instances; however, observational studies reported more extreme beneficial treatment effects compared with RCTs in 13 of 17 instances (P = 0.049). Sensitivity analyses limited to large RCTs, and using alternative meta-analysis models yielded similar results. Conclusion For the treatment of ACS, observational studies using PS methods produce treatment effect estimates that are of more extreme magnitude compared with those from RCTs, although the differences are rarely statistically significant. PMID:22711757

Massage Therapy for Fibromyalgia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Li, Yan-hui; Wang, Feng-yun; Feng, Chun-qing; Yang, Xia-feng; Sun, Yi-hua

2014-01-01

Background Although some studies evaluated the effectiveness of massage therapy for fibromyalgia (FM), the role of massage therapy in the management of FM remained controversial. Objective The purpose of this systematic review is to evaluate the evidence of massage therapy for patients with FM. Methods Electronic databases (up to June 2013) were searched to identify relevant studies. The main outcome measures were pain, anxiety, depression, and sleep disturbance. Two reviewers independently abstracted data and appraised risk of bias. The risk of bias of eligible studies was assessed based on Cochrane tools. Standardised mean difference (SMD) and 95% confidence intervals (CI) were calculated by more conservative random-effects model. And heterogeneity was assessed based on the I2 statistic. Results Nine randomized controlled trials involving 404 patients met the inclusion criteria. The meta-analyses showed that massage therapy with duration ≥5 weeks significantly improved pain (SMD, 0.62; 95% CI 0.05 to 1.20; p = 0.03), anxiety (SMD, 0.44; 95% CI 0.09 to 0.78; p = 0.01), and depression (SMD, 0.49; 95% CI 0.15 to 0.84; p = 0.005) in patients with FM, but not on sleep disturbance (SMD, 0.19; 95% CI −0.38 to 0.75; p = 0.52). Conclusion Massage therapy with duration ≥5 weeks had beneficial immediate effects on improving pain, anxiety, and depression in patients with FM. Massage therapy should be one of the viable complementary and alternative treatments for FM. However, given fewer eligible studies in subgroup meta-analyses and no evidence on follow-up effects, large-scale randomized controlled trials with long follow-up are warrant to confirm the current findings. PMID:24586677

A Meta-Analysis of Randomized Controlled Trials and Prospective Cohort Studies of Eicosapentaenoic and Docosahexaenoic Long-Chain Omega-3 Fatty Acids and Coronary Heart Disease Risk.

PubMed

Alexander, Dominik D; Miller, Paige E; Van Elswyk, Mary E; Kuratko, Connye N; Bylsma, Lauren C

2017-01-01

To conduct meta-analyses of randomized controlled trials (RCTs) to estimate the effect of eicosapentaenoic and docosahexaenoic acid (EPA+DHA) on coronary heart disease (CHD), and to conduct meta-analyses of prospective cohort studies to estimate the association between EPA+DHA intake and CHD risk. A systematic literature search of Ovid/Medline, PubMed, Embase, and the Cochrane Library from January 1, 1947, to November 2, 2015, was conducted; 18 RCTs and 16 prospective cohort studies examining EPA+DHA from foods or supplements and CHD, including myocardial infarction, sudden cardiac death, coronary death, and angina, were identified. Random-effects meta-analysis models were used to generate summary relative risk estimates (SRREs) and 95% CIs. Heterogeneity was examined in subgroup and sensitivity analyses and by meta-regression. Dose-response was evaluated in stratified dose or intake analyses. Publication bias assessments were performed. Among RCTs, there was a nonstatistically significant reduction in CHD risk with EPA+DHA provision (SRRE=0.94; 95% CI, 0.85-1.05). Subgroup analyses of data from RCTs indicated a statistically significant CHD risk reduction with EPA+DHA provision among higher-risk populations, including participants with elevated triglyceride levels (SRRE=0.84; 95% CI, 0.72-0.98) and elevated low-density lipoprotein cholesterol (SRRE=0.86; 95% CI, 0.76-0.98). Meta-analysis of data from prospective cohort studies resulted in a statistically significant SRRE of 0.82 (95% CI, 0.74-0.92) for higher intakes of EPA+DHA and risk of any CHD event. Results indicate that EPA+DHA may be associated with reducing CHD risk, with a greater benefit observed among higher-risk populations in RCTs. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

The effect of active video games on cognitive functioning in clinical and non-clinical populations: A meta-analysis of randomized controlled trials.

PubMed

Stanmore, Emma; Stubbs, Brendon; Vancampfort, Davy; de Bruin, Eling D; Firth, Joseph

2017-07-01

Physically-active video games ('exergames') have recently gained popularity for leisure and entertainment purposes. Using exergames to combine physical activity and cognitively-demanding tasks may offer a novel strategy to improve cognitive functioning. Therefore, this systematic review and meta-analysis was performed to establish effects of exergames on overall cognition and specific cognitive domains in clinical and non-clinical populations. We identified 17 eligible RCTs with cognitive outcome data for 926 participants. Random-effects meta-analyses found exergames significantly improved global cognition (g=0.436, 95% CI=0.18-0.69, p=0.001). Significant effects still existed when excluding waitlist-only controlled studies, and when comparing to physical activity interventions. Furthermore, benefits of exergames where observed for both healthy older adults and clinical populations with conditions associated with neurocognitive impairments (all p<0.05). Domain-specific analyses found exergames improved executive functions, attentional processing and visuospatial skills. The findings present the first meta-analytic evidence for effects of exergames on cognition. Future research must establish which patient/treatment factors influence efficacy of exergames, and explore neurobiological mechanisms of action. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

The effect of manual therapy and exercise in patients with chronic low back pain: Double blind randomized controlled trial.

PubMed

Ulger, Ozlem; Demirel, Aynur; Oz, Müzeyyen; Tamer, Seval

2017-11-06

To determine the effects of spinal stabilization exercises (SSE) and manual therapy methods on pain, function and quality of life (QoL) levels in individuals with chronic low back pain (CLBP). A total of one-hundred thirteen patients diagnosed as CLBP were enrolled to the study. The patients allocated into Spinal Stabilization group (SG) and manual therapy group (MG), randomly. While SSE performed in SG, soft tissue mobilizations, muscle-energy techniques, joint mobilizations and manipulations were performed in MG. While the severity of pain was assessed with Visual Analog Scale (VAS), Oswestry Disability Index (ODI) and Short Form 36 (SF-36) assessments were performed to evaluate the functional status and QoL, respectively. All assessments were repeated before and after the treatment. Intragroup analyses both treatments were effective in terms of sub parameters of pain, function and life quality (p< 0.05). Inter group analyses, there was more reduction in pain and improvement in functional status in favor of MG (p< 0.05). This study showed that SSE and manual therapy methods have the same effects on QoL, while the manual treatment is more effective on the pain and functional parameters in particular.

Analyzing Milestones in Smoking Cessation: Illustration in a Nicotine Patch Trial in Adult Smokers

ERIC Educational Resources Information Center

Shiffman, Saul; Scharf, Deborah M.; Shadel, William G.; Gwaltney, Chad J.; Dang, Qianyu; Paton, Stephanie M.; Clark, Duncan B.

2006-01-01

Tests of addiction treatments seldom reveal where treatment exercises its effect (i.e., promoting initial abstinence, preventing lapses, and/or impeding progression from lapse to relapse). The authors illustrate analyses distinguishing effects on these milestones in a randomized trial of high-dose nicotine patch (35 mg; n = 188) versus placebo (n…

The crime prevention value of hot spots policing.

PubMed

Braga, Anthony A

2006-08-01

This paper reviews the available research evidence on the effectiveness of hot spots policing programs in reducing crime and disorder. The research identified five randomized controlled experiments and four non-equivalent control group quasi-experiments evaluating the effects of hot spots policing interventions on crime. Seven of nine selected evaluations reported noteworthy crime and disorder reductions. Meta-analyses of the randomized experiments revealed statistically significant mean effect sizes favoring hot spots policing interventions in reducing citizen calls for service in treatment places relative to control places. When immediate spatial displacement was measured, it was very limited and unintended crime prevention benefits were associated with the hot spots policing programs. The results of this review suggest that hot spots policing is an effective crime prevention strategy.

Random regression models using different functions to model milk flow in dairy cows.

PubMed

Laureano, M M M; Bignardi, A B; El Faro, L; Cardoso, V L; Tonhati, H; Albuquerque, L G

2014-09-12

We analyzed 75,555 test-day milk flow records from 2175 primiparous Holstein cows that calved between 1997 and 2005. Milk flow was obtained by dividing the mean milk yield (kg) of the 3 daily milking by the total milking time (min) and was expressed as kg/min. Milk flow was grouped into 43 weekly classes. The analyses were performed using a single-trait Random Regression Models that included direct additive genetic, permanent environmental, and residual random effects. In addition, the contemporary group and linear and quadratic effects of cow age at calving were included as fixed effects. Fourth-order orthogonal Legendre polynomial of days in milk was used to model the mean trend in milk flow. The additive genetic and permanent environmental covariance functions were estimated using random regression Legendre polynomials and B-spline functions of days in milk. The model using a third-order Legendre polynomial for additive genetic effects and a sixth-order polynomial for permanent environmental effects, which contained 7 residual classes, proved to be the most adequate to describe variations in milk flow, and was also the most parsimonious. The heritability in milk flow estimated by the most parsimonious model was of moderate to high magnitude.

Quality of surgical randomized controlled trials for acute cholecystitis: assessment based on CONSORT and additional check items.

PubMed

Shikata, Satoru; Nakayama, Takeo; Yamagishi, Hisakazu

2008-01-01

In this study, we conducted a limited survey of reports of surgical randomized controlled trials, using the consolidated standards of reporting trials (CONSORT) statement and additional check items to clarify problems in the evaluation of surgical reports. A total of 13 randomized trials were selected from two latest review articles on biliary surgery. Each randomized trial was evaluated according to 28 quality measures that comprised items from the CONSORT statement plus additional items. Analysis focused on relationships between the quality of each study and the estimated effect gap ("pooled estimate in meta-analysis" -- "estimated effect of each study"). No definite relationships were found between individual study quality and the estimated effect gap. The following items could have been described but were not provided in almost all the surgical RCT reports: "clearly defined outcomes"; "details of randomization"; "participant flow charts"; "intention-to-treat analysis"; "ancillary analyses"; and "financial conflicts of interest". The item, "participation of a trial methodologist in the study" was not found in any of the reports. Although the quality of reporting trials is not always related to a biased estimation of treatment effect, the items used for quality measures must be described to enable readers to evaluate the quality and applicability of the reporting. Further development of an assessment tool is needed for items specific to surgical randomized controlled trials.

Sample size considerations when groups are the appropriate unit of analyses

PubMed Central

Sadler, Georgia Robins; Ko, Celine Marie; Alisangco, Jennifer; Rosbrook, Bradley P.; Miller, Eric; Fullerton, Judith

2007-01-01

This paper discusses issues to be considered by nurse researchers when groups should be used as a unit of randomization. Advantages and disadvantages are presented, with statistical calculations needed to determine effective sample size. Examples of these concepts are presented using data from the Black Cosmetologists Promoting Health Program. Different hypothetical scenarios and their impact on sample size are presented. Given the complexity of calculating sample size when using groups as a unit of randomization, it’s advantageous for researchers to work closely with statisticians when designing and implementing studies that anticipate the use of groups as the unit of randomization. PMID:17693219

Acupuncture-Related Techniques for Psoriasis: A Systematic Review with Pairwise and Network Meta-Analyses of Randomized Controlled Trials.

PubMed

Yeh, Mei-Ling; Ko, Shu-Hua; Wang, Mei-Hua; Chi, Ching-Chi; Chung, Yu-Chu

2017-12-01

There has be a large body of evidence on the pharmacological treatments for psoriasis, but whether nonpharmacological interventions are effective in managing psoriasis remains largely unclear. This systematic review conducted pairwise and network meta-analyses to determine the effects of acupuncture-related techniques on acupoint stimulation for the treatment of psoriasis and to determine the order of effectiveness of these remedies. This study searched the following databases from inception to March 15, 2016: Medline, PubMed, Cochrane Central Register of Controlled Trials, EBSCO (including Academic Search Premier, American Doctoral Dissertations, and CINAHL), Airiti Library, and China National Knowledge Infrastructure. Randomized controlled trials (RCTs) on the effects of acupuncture-related techniques on acupoint stimulation as intervention for psoriasis were independently reviewed by two researchers. A total of 13 RCTs with 1,060 participants were included. The methodological quality of included studies was not rigorous. Acupoint stimulation, compared with nonacupoint stimulation, had a significant treatment for psoriasis. However, the most common adverse events were thirst and dry mouth. Subgroup analysis was further done to confirm that the short-term treatment effect was superior to that of the long-term effect in treating psoriasis. Network meta-analysis identified acupressure or acupoint catgut embedding, compared with medication, and had a significant effect for improving psoriasis. It was noted that acupressure was the most effective treatment. Acupuncture-related techniques could be considered as an alternative or adjuvant therapy for psoriasis in short term, especially of acupressure and acupoint catgut embedding. This study recommends further well-designed, methodologically rigorous, and more head-to-head randomized trials to explore the effects of acupuncture-related techniques for treating psoriasis.

Receipt of Preventive Services After Oregon's Randomized Medicaid Experiment.

PubMed

Marino, Miguel; Bailey, Steffani R; Gold, Rachel; Hoopes, Megan J; O'Malley, Jean P; Huguet, Nathalie; Heintzman, John; Gallia, Charles; McConnell, K John; DeVoe, Jennifer E

2016-02-01

It is predicted that gaining health insurance via the Affordable Care Act will result in increased rates of preventive health services receipt in the U.S., primarily based on self-reported findings from previous health insurance expansion studies. This study examined the long-term (36-month) impact of Oregon's 2008 randomized Medicaid expansion ("Oregon Experiment") on receipt of 12 preventive care services in community health centers using electronic health record data. Demographic data from adult (aged 19-64 years) Oregon Experiment participants were probabilistically matched to electronic health record data from 49 Oregon community health centers within the OCHIN community health information network (N=10,643). Intent-to-treat analyses compared receipt of preventive services over a 36-month (2008-2011) period among those randomly assigned to apply for Medicaid versus not assigned, and instrumental variable analyses estimated the effect of actually gaining Medicaid coverage on preventive services receipt (data collected in 2012-2014; analysis performed in 2014-2015). Intent-to-treat analyses revealed statistically significant differences between patients randomly assigned to apply for Medicaid (versus not assigned) for 8 of 12 assessed preventive services. In intent-to-treat analyses, Medicaid coverage significantly increased the odds of receipt of most preventive services (ORs ranging from 1.04 [95% CI=1.02, 1.06] for smoking assessment to 1.27 [95% CI=1.02, 1.57] for mammography). Rates of preventive services receipt will likely increase as community health center patients gain insurance through Affordable Care Act expansions. Continued effort is needed to increase health insurance coverage in an effort to decrease health disparities in vulnerable populations. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Receipt of Preventive Services After Oregon’s Randomized Medicaid Experiment

PubMed Central

Marino, Miguel; Bailey, Steffani R.; Gold, Rachel; Hoopes, Megan J.; O’Malley, Jean P.; Huguet, Nathalie; Heintzman, John; Gallia, Charles; McConnell, K. John; DeVoe, Jennifer E.

2015-01-01

Introduction It is predicted that gaining health insurance via the Affordable Care Act will result in increased rates of preventive health services receipt in the U.S, primarily based on self-reported findings from previous health insurance expansion studies. This study examined the long-term (36-month) impact of Oregon’s 2008 randomized Medicaid expansion (“Oregon Experiment”) on receipt of 12 preventive care services in community health centers using electronic health record data. Methods Demographic data from adult (aged 19–64 years) Oregon Experiment participants were probabilistically matched to electronic health record data from 49 Oregon community health centers within the OCHIN community health information network (N=10,643). Intent-to-treat analyses compared receipt of preventive services over a 36-month (2008–2011) period among those randomly assigned to apply for Medicaid versus not assigned, and instrumental variable analyses estimated the effect of actually gaining Medicaid coverage on preventive services receipt (data collected in 2012–2014; analysis performed in 2014–2015). Results Intent-to-treat analyses revealed statistically significant differences between patients randomly assigned to apply for Medicaid (versus not assigned) for eight of 12 assessed preventive services. In intent-to-treat[MM1] analyses, Medicaid coverage significantly increased the odds of receipt of most preventive services (ORs ranging from 1.04 [95% CI=1.02, 1.06] for smoking assessment to 1.27 [95% CI=1.02, 1.57] for mammography). Conclusions Rates of preventive services receipt will likely increase as community health center patients gain insurance through Affordable Care Act expansions. Continued effort is needed to increase health insurance coverage in an effort to decrease health disparities in vulnerable populations. PMID:26497264

Examining the Causal Role of Leptin in Alzheimer Disease: A Mendelian Randomization Study.

PubMed

Romo, Matthew L; Schooling, C Mary

2017-01-01

Observational evidence regarding the role of leptin in Alzheimer disease (AD) is conflicting. We sought to determine the causal role of circulating leptin and soluble plasma leptin receptor (sOB-R) levels in AD using a separate-sample Mendelian randomization study. Single nucleotide polymorphisms (SNPs) independently and solely predictive of log-transformed leptin (rs10487505 [LEP], rs780093 [GCKR], rs900400 [CCNL1], rs6071166 [SLC32A1], and rs6738627 [COBLL1]) and of sOB-R (rs1137101 [LEPR], rs2767485 [LEPR], and rs1751492 [LEPR]) levels (ng/mL) were obtained from 2 previously reported genome-wide association studies. We obtained associations of leptin and sOB-R levels with AD using inverse variance weighting with fixed effects by combining Wald estimates for each SNP. Sensitivity analyses included using weighted median and MR-Egger methods and repeating the analyses using only SNPs of genome-wide significance. Using inverse variance weighting, genetically predicted circulating leptin levels were not associated with AD, albeit with wide confidence intervals (CIs): odds ratio (OR) 0.99 per log-transformed ng/mL; 95% CI 0.55-1.78. Similarly, the association of sOB-R with AD was null using inverse variance weighting (OR 1.08 per log-transformed ng/mL; 95% CI 0.83-1.41). Results from our sensitivity analyses confirmed our findings. In this first Mendelian randomization study estimating the causal effect of leptin on AD, we did not find an effect of genetically predicted circulating leptin and sOB-R levels on AD. As such, this study suggests that leptin is unlikely to be a major contributor to AD, although the wide CIs preclude a definitive assessment. © 2017 S. Karger AG, Basel.

Interventions to lower the glycemic response to carbohydrate foods with a low-viscosity fiber (resistant maltodextrin): meta-analysis of randomized controlled trials.

PubMed

Livesey, Geoffrey; Tagami, Hiroyuki

2009-01-01

The glycemic response to diet has been linked with noncommunicable diseases and is reduced by low-palatable, viscous, soluble fiber (1). Whether a palatable, low-viscous, soluble fiber such as resistant maltodextrin (RMD) has the same effect is unclear. The objective was to assess evidence on the attenuation of the blood glucose response to foods by < or = 10 g RMD in healthy adults. We conducted a systematic review of randomized, placebo-controlled trials with the use of fixed- and random-effects meta-analyses and meta-regression models. We found data from 37 relevant trials to April 2007. These trials investigated the attenuation of the glycemic response to rice, noodles, pastry, bread, and refined carbohydrates that included 30-173 g available carbohydrate. RMD was administered in drinks or liquid foods or solid foods. Placebo drinks and foods excluded RMD. Percentage attenuation was significant, dose-dependent, and independent of the amount of available carbohydrate coingested. Attenuation of the glycemic response to starchy foods by 6 g RMD in drinks approached approximately 20%, but when placed directly into foods was approximately 10% -- significant (P < 0.001) by both modes of administration. Study quality analyses, funnel plots, and trim-and-fill analyses uncovered no cause of significant systematic bias. Studies from authors affiliated with organizations for-profit were symmetrical without heterogeneity, whereas marginal asymmetry and significant heterogeneity arose among studies involving authors from nonprofit organizations because of some imprecise studies. A nonviscous palatable soluble polysaccharide can attenuate the glycemic response to carbohydrate foods. Evidence of an effect was stronger for RMD in drinks than in foods.

A Hybrid Approach to Protect Palmprint Templates

PubMed Central

Sun, Dongmei; Xiong, Ke; Qiu, Zhengding

2014-01-01

Biometric template protection is indispensable to protect personal privacy in large-scale deployment of biometric systems. Accuracy, changeability, and security are three critical requirements for template protection algorithms. However, existing template protection algorithms cannot satisfy all these requirements well. In this paper, we propose a hybrid approach that combines random projection and fuzzy vault to improve the performances at these three points. Heterogeneous space is designed for combining random projection and fuzzy vault properly in the hybrid scheme. New chaff point generation method is also proposed to enhance the security of the heterogeneous vault. Theoretical analyses of proposed hybrid approach in terms of accuracy, changeability, and security are given in this paper. Palmprint database based experimental results well support the theoretical analyses and demonstrate the effectiveness of proposed hybrid approach. PMID:24982977

A hybrid approach to protect palmprint templates.

PubMed

Liu, Hailun; Sun, Dongmei; Xiong, Ke; Qiu, Zhengding

2014-01-01

Biometric template protection is indispensable to protect personal privacy in large-scale deployment of biometric systems. Accuracy, changeability, and security are three critical requirements for template protection algorithms. However, existing template protection algorithms cannot satisfy all these requirements well. In this paper, we propose a hybrid approach that combines random projection and fuzzy vault to improve the performances at these three points. Heterogeneous space is designed for combining random projection and fuzzy vault properly in the hybrid scheme. New chaff point generation method is also proposed to enhance the security of the heterogeneous vault. Theoretical analyses of proposed hybrid approach in terms of accuracy, changeability, and security are given in this paper. Palmprint database based experimental results well support the theoretical analyses and demonstrate the effectiveness of proposed hybrid approach.

Mind-Body Interventions for Irritable Bowel Syndrome Patients in the Chinese Population: a Systematic Review and Meta-Analysis.

PubMed

Wang, Weidong; Wang, Fang; Fan, Feng; Sedas, Ana Cristina; Wang, Jian

2017-04-01

The aim of this study is to identify and assess evidence related to the efficacy of mind-body interventions on irritable bowel syndrome (IBS) in the Chinese population. Drawn from Chinese databases, nine RCTs and three Q-E studies were included in the systematic review. The methodological quality of RCTs was evaluated based on the following criteria: adequate sequence generation, allocation concealment, blinding, completeness of outcome data, selective reporting, and other potential biases. For continuous variables, the effect size (ES) was determined by calculating the standardized mean difference between groups. For dichotomous variables, the ES was determined by calculating the risk ratio (RR) between groups. Given the heterogeneity between the trials and the small number of studies included, both random effects and fixed effects models were used. The inverse variance method was used for pooling. Statistical analyses were performed using Review Manager version 5.0. The total number of papers identified was 710: 462 from English language databases and 248 from Chinese language databases. Twelve studies met our eligibility criteria. Among the studies selected, three were Q-E studies the rest RCTs. Two studies described the randomization process. None of the studies reported allocation concealment nor blinding. Seven studies reported no dropouts. One of the studies mentioned the total amount of dropouts; though the reason for dropping out was not referenced. The other four studies did not clearly report dropouts. With the exception of three studies, there was inadequate information to determine biased reporting for the majority; the level of risk for bias in these studies is unclear. Finally, six meta-analyses were performed. One was conducted with four randomized controlled trials (RCTs) that used cure rate as outcome measures to evaluate gastrointestinal (GI) symptoms, which suggested that mind-body interventions were effective in improving GI symptoms (random effects model: RR = 1.08; 95 % CI 1.01 to 1.17; fixed effects model: RR = 1.07; 95 % CI 1.01 to 1.12). The remaining five were conducted in three RCTs, which suggested that mind-body interventions were effective in improving several aspects of quality of life, including interference with activity (random effects and fixed effects models: SMD = 0.64; 95 % CI 0.41 to 0.86), body image (random effects model: SMD = 0.36; 95 % CI 0.06 to 0.67; fixed effects model: SMD = 0.33; 95 % CI 0.11 to 0.55), health worry (random effects and fixed effects models: SMD = 0.67; 95 % CI 0.44 to 0.90), food avoidance (random effects and fixed effects models: SMD = 0.45; 95 % CI 0.23 to 0.68), and social reaction (random effects model: SMD = 0.79; 95 % CI 0.47 to 1.12; fixed effects model: SMD = 0.78; 95 % CI 0.55 to 1.01), as measured by Irritable Bowel Syndrome Quality of Life Questionnaire ( IBS-QOL). Mind-body interventions may have the potential to improve GI symptoms in Chinese patients with IBS. The improvement of GI symptoms was also accompanied with the improvement of various outcomes, including depression, anxiety, and quality of life, just to mention a few. However, the published studies generally had significant methodological limitations. Future clinical trials with rigorous research design are needed in this field. More studies focusing on the mind-body interventions originated in China, such as tai chi and qi gong should be encouraged.

Correction of confounding bias in non-randomized studies by appropriate weighting.

PubMed

Schmoor, Claudia; Gall, Christine; Stampf, Susanne; Graf, Erika

2011-03-01

In non-randomized studies, the assessment of a causal effect of treatment or exposure on outcome is hampered by possible confounding. Applying multiple regression models including the effects of treatment and covariates on outcome is the well-known classical approach to adjust for confounding. In recent years other approaches have been promoted. One of them is based on the propensity score and considers the effect of possible confounders on treatment as a relevant criterion for adjustment. Another proposal is based on using an instrumental variable. Here inference relies on a factor, the instrument, which affects treatment but is thought to be otherwise unrelated to outcome, so that it mimics randomization. Each of these approaches can basically be interpreted as a simple reweighting scheme, designed to address confounding. The procedures will be compared with respect to their fundamental properties, namely, which bias they aim to eliminate, which effect they aim to estimate, and which parameter is modelled. We will expand our overview of methods for analysis of non-randomized studies to methods for analysis of randomized controlled trials and show that analyses of both study types may target different effects and different parameters. The considerations will be illustrated using a breast cancer study with a so-called Comprehensive Cohort Study design, including a randomized controlled trial and a non-randomized study in the same patient population as sub-cohorts. This design offers ideal opportunities to discuss and illustrate the properties of the different approaches. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The statistical pitfalls of the partially randomized preference design in non-blinded trials of psychological interventions.

PubMed

Gemmell, Isla; Dunn, Graham

2011-03-01

In a partially randomized preference trial (PRPT) patients with no treatment preference are allocated to groups at random, but those who express a preference receive the treatment of their choice. It has been suggested that the design can improve the external and internal validity of trials. We used computer simulation to illustrate the impact that an unmeasured confounder could have on the results and conclusions drawn from a PRPT. We generated 4000 observations ("patients") that reflected the distribution of the Beck Depression Index (DBI) in trials of depression. Half were randomly assigned to a randomized controlled trial (RCT) design and half were assigned to a PRPT design. In the RCT, "patients" were evenly split between treatment and control groups; whereas in the preference arm, to reflect patient choice, 87.5% of patients were allocated to the experimental treatment and 12.5% to the control. Unadjusted analyses of the PRPT data consistently overestimated the treatment effect and its standard error. This lead to Type I errors when the true treatment effect was small and Type II errors when the confounder effect was large. The PRPT design is not recommended as a method of establishing an unbiased estimate of treatment effect due to the potential influence of unmeasured confounders. Copyright © 2011 John Wiley & Sons, Ltd.

Subharmonic response of a single-degree-of-freedom nonlinear vibro-impact system to a narrow-band random excitation.

PubMed

Haiwu, Rong; Wang, Xiangdong; Xu, Wei; Fang, Tong

2009-08-01

The subharmonic response of single-degree-of-freedom nonlinear vibro-impact oscillator with a one-sided barrier to narrow-band random excitation is investigated. The narrow-band random excitation used here is a filtered Gaussian white noise. The analysis is based on a special Zhuravlev transformation, which reduces the system to one without impacts, or velocity jumps, thereby permitting the applications of asymptotic averaging over the "fast" variables. The averaged stochastic equations are solved exactly by the method of moments for the mean-square response amplitude for the case of linear system with zero offset. A perturbation-based moment closure scheme is proposed and the formula of the mean-square amplitude is obtained approximately for the case of linear system with nonzero offset. The perturbation-based moment closure scheme is used once again to obtain the algebra equation of the mean-square amplitude of the response for the case of nonlinear system. The effects of damping, detuning, nonlinear intensity, bandwidth, and magnitudes of random excitations are analyzed. The theoretical analyses are verified by numerical results. Theoretical analyses and numerical simulations show that the peak amplitudes may be strongly reduced at large detunings or large nonlinear intensity.

Understanding Statistical Power in Cluster Randomized Trials: Challenges Posed by Differences in Notation and Terminology

ERIC Educational Resources Information Center

Spybrook, Jessaca; Hedges, Larry; Borenstein, Michael

2014-01-01

Research designs in which clusters are the unit of randomization are quite common in the social sciences. Given the multilevel nature of these studies, the power analyses for these studies are more complex than in a simple individually randomized trial. Tools are now available to help researchers conduct power analyses for cluster randomized…

Clinical and Molecular Epidemiology of Extended-Spectrum Beta-Lactamase-Producing Klebsiella spp.: A Systematic Review and Meta-Analyses

PubMed Central

Hendrik, Tirza C.; Voor in ‘t holt, Anne F.; Vos, Margreet C.

2015-01-01

Healthcare-related infections caused by extended-spectrum beta-lactamase (ESBL)-producing Klebsiella spp. are of major concern. To control transmission, deep understanding of the transmission mechanisms is needed. This systematic review aimed to identify risk factors and sources, clonal relatedness using molecular techniques, and the most effective control strategies for ESBL-producing Klebsiella spp. A systematic search of PubMed, Embase, and Outbreak Database was performed. We identified 2771 articles from November 25th, 1960 until April 7th, 2014 of which 148 were included in the systematic review and 23 in a random-effects meta-analysis study. The random-effects meta-analyses showed that underlying disease or condition (odds ratio [OR] = 6.25; 95% confidence interval [CI] = 2.85 to 13.66) generated the highest pooled estimate. ESBL-producing Klebsiella spp. were spread through person-to-person contact and via sources in the environment; we identified both monoclonal and polyclonal presence. Multi-faceted interventions are needed to prevent transmission of ESBL-producing Klebsiella spp. PMID:26485570

Practice-based evidence study design for comparative effectiveness research.

PubMed

Horn, Susan D; Gassaway, Julie

2007-10-01

To describe a new, rigorous, comprehensive practice-based evidence for clinical practice improvement (PBE-CPI) study methodology, and compare its features, advantages, and disadvantages to those of randomized controlled trials and sophisticated statistical methods for comparative effectiveness research. PBE-CPI incorporates natural variation within data from routine clinical practice to determine what works, for whom, when, and at what cost. It uses the knowledge of front-line caregivers, who develop study questions and define variables as part of a transdisciplinary team. Its comprehensive measurement framework provides a basis for analyses of significant bivariate and multivariate associations between treatments and outcomes, controlling for patient differences, such as severity of illness. PBE-CPI studies can uncover better practices more quickly than randomized controlled trials or sophisticated statistical methods, while achieving many of the same advantages. We present examples of actionable findings from PBE-CPI studies in postacute care settings related to comparative effectiveness of medications, nutritional support approaches, incontinence products, physical therapy activities, and other services. Outcomes improved when practices associated with better outcomes in PBE-CPI analyses were adopted in practice.

Sensitivity of breeding values for carcass traits of meat-type quail to changes in dietary (methionine + cystine):lysine ratio using reaction norm models.

PubMed

Miranda, J A; Pires, A V; Abreu, L R A; Mota, L F M; Silva, M A; Bonafé, C M; Lima, H J D; Martins, P G M A

2016-12-01

Our objective was to evaluate changes in breeding values for carcass traits of two meat-type quail (Coturnix coturnix) strains (LF1 and LF2) to changes in the dietary (methionine + cystine):lysine ([Met + Cys]:Lys) ratio due to genotype by environment (G × E) interaction via reaction norm. A total of 7000 records of carcass weight and yield were used for analyses. During the initial phase (from hatching to day 21), five diets with increasing (Met + Cys):Lys ratios (0.61, 0.66, 0.71, 0.76 and 0.81), containing 26.1% crude protein and 2900 kcal ME/kg, were evaluated. Analyses were performed using random regression models that included linear functions of sex (fixed effect) and breeding value (random effect) for carcass weight and yield, without and with heterogeneous residual variance adjustment. Both fixed and random effects were modelled using Legendre polynomials of second order. Genetic variance and heritability estimates were affected by both (Met + Cys):Lys ratio and strain. We observed that a G × E interaction was present, with changes in the breeding value ranking. Therefore, genetic evaluation for carcass traits should be performed under the same (Met + Cys):Lys ratio in which quails are raised. © 2016 Blackwell Verlag GmbH.

A randomized controlled trial evaluating the effect of ethinyl estradiol during clomiphene citrate cycles among women with polycystic ovary syndrome.

PubMed

Moini, Ashraf; Ahmadi, Firoozeh; Jahangiri, Nadia; Ahmadi, Jila; Akhoond, Mohammad Reza

2015-11-01

To investigate the effects of low-dose ethinyl estradiol (EE) on the clinical pregnancy rate among women with polycystic ovary syndrome (PCOS) undergoing ovulation induction with clomiphene citrate (CC). Between March 12, 2011, and February 10, 2013, a randomized, double-blind, placebo-controlled trial was conducted at the Royan Institute Research Center, Tehran, Iran, among women with PCOS who were aged 25-30 years, were undergoing their first intrauterine insemination cycle, and had a history (≥2 years) of infertility, oligomenorrhea, or amenorrhea. Participants were randomly allocated to receive EE (0.05 mg daily for 5 days) or placebo, co-administered with CC cycles (100 mg daily for 5 days). The primary outcome was clinical pregnancy rate. Analyses were per protocol: patients who discontinued the intervention were excluded. Analyses included 45 women who received CC and EE, and 50 women who received CC and placebo. The number of women who achieved a clinical pregnancy was higher among participants who received CC and EE (13 [29%]) than among those in the control group (5 [10%]; P =0 .02). No adverse effects of EE were reported. The combination of CC and EE seems to increase the clinical pregnancy rate among women with PCOS undergoing intrauterine insemination. ClinicalTrials.gov:NCT01219101. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

[Memantine as add-on medication to acetylcholinesterase inhibitor therapy for Alzheimer dementia].

PubMed

Haussmann, R; Donix, M

2017-01-01

Currently available data indicate superior therapeutic effects of combination treatment for Alzheimer dementia with memantine and acetylcholine esterase inhibitors in certain clinical contexts. Out of five randomized, placebo-controlled, double-blind trials two showed superior therapeutic effects in comparison to monotherapy with acetylcholinesterase inhibitors regarding various domains. Recently published meta-analyses and cost-benefit analyses also showed positive results. Recently published German guidelines for dementia treatment also take these new data into account and recommend combination treatment in patients with severe dementia on stable donepezil medication. This article gives an overview of current evidence for combination therapy.

A randomized clinical trial of cognitive behavioral therapy and interpersonal psychotherapy for panic disorder with agoraphobia.

PubMed

Vos, S P F; Huibers, M J H; Diels, L; Arntz, A

2012-12-01

Interpersonal psychotherapy (IPT) seems to be as effective as cognitive behavioral therapy (CBT) in the treatment of major depression. Because the onset of panic attacks is often related to increased interpersonal life stress, IPT has the potential to also treat panic disorder. To date, a preliminary open trial yielded promising results but there have been no randomized controlled trials directly comparing CBT and IPT for panic disorder. This study aimed to directly compare the effects of CBT versus IPT for the treatment of panic disorder with agoraphobia. Ninety-one adult patients with a primary diagnosis of DSM-III or DSM-IV panic disorder with agoraphobia were randomized. Primary outcomes were panic attack frequency and an idiosyncratic behavioral test. Secondary outcomes were panic and agoraphobia severity, panic-related cognitions, interpersonal functioning and general psychopathology. Measures were taken at 0, 3 and 4 months (baseline, end of treatment and follow-up). Intention-to-treat (ITT) analyses on the primary outcomes indicated superior effects for CBT in treating panic disorder with agoraphobia. Per-protocol analyses emphasized the differences between treatments and yielded larger effect sizes. Reductions in the secondary outcomes were equal for both treatments, except for agoraphobic complaints and behavior and the credibility ratings of negative interpretations of bodily sensations, all of which decreased more in CBT. CBT is the preferred treatment for panic disorder with agoraphobia compared to IPT. Mechanisms of change should be investigated further, along with long-term outcomes.

Chemotherapy in advanced ovarian cancer: four systematic meta-analyses of individual patient data from 37 randomized trials. Advanced Ovarian Cancer Trialists' Group.

PubMed Central

Aabo, K.; Adams, M.; Adnitt, P.; Alberts, D. S.; Athanazziou, A.; Barley, V.; Bell, D. R.; Bianchi, U.; Bolis, G.; Brady, M. F.; Brodovsky, H. S.; Bruckner, H.; Buyse, M.; Canetta, R.; Chylak, V.; Cohen, C. J.; Colombo, N.; Conte, P. F.; Crowther, D.; Edmonson, J. H.; Gennatas, C.; Gilbey, E.; Gore, M.; Guthrie, D.; Yeap, B. Y.

1998-01-01

The purpose of this systematic study was to provide an up to date and reliable quantitative summary of the relative benefits of various types of chemotherapy (non-platinum vs platinum, single-agent vs combination and carboplatin vs cisplatin) in the treatment of advanced ovarian cancer. Also, to investigate whether well-defined patient subgroups benefit more or less from cisplatin- or carboplatin-based therapy. Meta-analyses were based on updated individual patient data from all available randomized controlled trials (published and unpublished), including 37 trials, 5667 patients and 4664 deaths. The results suggest that platinum-based chemotherapy is better than non-platinum therapy, show a trend in favour of platinum combinations over single-agent platinum, and suggest that cisplatin and carboplatin are equally effective. There is no good evidence that cisplatin is more or less effective than carboplatin in any particular subgroup of patients. Images Figure 1 Figure 2 Figure 3 PMID:9836481

Cost-Effectiveness of Tight Control of Inflammation in Early Psoriatic Arthritis: Economic Analysis of a Multicenter Randomized Controlled Trial.

PubMed

O'Dwyer, John L; Meads, David M; Hulme, Claire T; Mcparland, Lucy; Brown, Sarah; Coates, Laura C; Moverley, Anna R; Emery, Paul; Conaghan, Philip G; Helliwell, Philip S

2018-03-01

Treat-to-target approaches have proved to be effective in rheumatoid arthritis, but have not been studied in psoriatic arthritis (PsA). This study was undertaken to examine the cost-effectiveness of tight control (TC) of inflammation in early PsA compared to standard care. Cost-effectiveness analyses were undertaken alongside a UK-based, open-label, multicenter, randomized controlled trial. Taking the perspective of the health care sector, effectiveness was measured using the 3-level EuroQol 5-domain, which allows for the calculation of quality-adjusted life-years (QALYs). Incremental cost-effectiveness ratios (ICERs) are presented, which represent the additional cost per QALY gained over a 48-week time horizon. Sensitivity analyses are presented assessing the impact of variations in the analytical approach and assumptions on the cost-effectiveness estimates. The mean cost and QALYs were higher in the TC group: £4,198 versus £2,000 and 0.602 versus 0.561. These values yielded an ICER of £53,948 per QALY. Bootstrapped uncertainty analysis suggests that the TC has a 0.07 probability of being cost-effective at a £20,000 threshold. Stratified analysis suggests that with certain costs being controlled, an ICER of £24,639 can be calculated for patients with a higher degree of disease severity. A tight control strategy to treat PsA is an effective intervention in the treatment pathway; however, this study does not find tight control to be cost-effective in most analyses. Lower drug prices, targeting polyarthritis patients, or reducing the frequency of rheumatology visits may improve value for money metrics in future studies. © 2017, American College of Rheumatology.

Effectiveness of a selective intervention program targeting personality risk factors for alcohol misuse among young adolescents: results of a cluster randomized controlled trial.

PubMed

Lammers, Jeroen; Goossens, Ferry; Conrod, Patricia; Engels, Rutger; Wiers, Reinout W; Kleinjan, Marloes

2015-07-01

The effectiveness of Preventure was tested on drinking behaviour of young adolescents in secondary education in the Netherlands. A cluster randomized controlled trial was carried out, with participants assigned randomly to a two-session coping skills intervention or a control no-intervention condition. Fifteen secondary schools throughout the Netherlands; seven schools in the intervention and eight schools in the control condition. A total of 699 adolescents aged 13-15 years participated, 343 allocated to the intervention and 356 to the control condition, with drinking experience and elevated scores in either negative thinking, anxiety sensitivity, impulsivity or sensation-seeking. Preventure is a selective school-based alcohol prevention programme targeting personality risk factors. The comparator was a no-intervention control. The effects of the intervention on the primary outcome past-month binge drinking, and the secondary outcomes binge drinking frequency, alcohol use, alcohol frequency and problem drinking, were examined. The primary analyses of interest were intervention main effects at 12 months post-intervention. In addition, intervention effects on the linear development of binge drinking using a latent-growth curve approach were examined. Binge drinking rates were not significantly different between the intervention (42.9%) and control group (49.2%) at 12 months follow-up [odds ratio (OR) = 1.05, confidence interval (CI) = 0.99, 1.11]. Intention-to-treat analyses revealed no significant intervention effects on alcohol use (53.9 versus 61.5%; OR = 0.99, CI = 0.86, 1.14) and problem drinking (37.0 versus 44.7%; OR = 1.03, CI = 0.92, 1.10) at 12 months follow-up. The post-hoc latent-growth analyses revealed significant effects on the development of binge drinking (β = -0.16, P = 0.05), and binge drinking frequency (β = -0.14, P = 0.05). The alcohol prevention programme, Preventure, appears to have little or no effect on overall prevalence of binge drinking in adolescents in the Netherlands but may reduce the development of binge drinking over time. © 2015 Society for the Study of Addiction.

An Examination of Mediators of the Transfer of Cognitive Speed of Processing Training to Everyday Functional Performance

PubMed Central

Edwards, Jerri D.; Ruva, Christine L.; O’Brien, Jennifer L.; Haley, Christine B.; Lister, Jennifer J.

2013-01-01

The purpose of these analyses was to examine mediators of the transfer of cognitive speed of processing training to improved everyday functional performance (Edwards, Wadley, Vance, Roenker, & Ball, 2005). Cognitive speed of processing and visual attention (as measured by the Useful Field of View Test; UFOV) were examined as mediators of training transfer. Secondary data analyses were conducted from the Staying Keen in Later Life (SKILL) study, a randomized cohort study including 126 community dwelling adults 63 to 87 years of age. In the SKILL study, participants were randomized to an active control group or cognitive speed of processing training (SOPT), a non-verbal, computerized intervention involving perceptual practice of visual tasks. Prior analyses found significant effects of training as measured by the UFOV and Timed Instrumental Activities of Daily Living (TIADL) Tests. Results from the present analyses indicate that speed of processing for a divided attention task significantly mediated the effect of SOPT on everyday performance (e.g., TIADL) in a multiple mediation model accounting for 91% of the variance. These findings suggest that everyday functional improvements found from SOPT are directly attributable to improved UFOV performance, speed of processing for divided attention in particular. Targeting divided attention in cognitive interventions may be important to positively affect everyday functioning among older adults. PMID:23066808

Using Big Data to Emulate a Target Trial When a Randomized Trial Is Not Available.

PubMed

Hernán, Miguel A; Robins, James M

2016-04-15

Ideally, questions about comparative effectiveness or safety would be answered using an appropriately designed and conducted randomized experiment. When we cannot conduct a randomized experiment, we analyze observational data. Causal inference from large observational databases (big data) can be viewed as an attempt to emulate a randomized experiment-the target experiment or target trial-that would answer the question of interest. When the goal is to guide decisions among several strategies, causal analyses of observational data need to be evaluated with respect to how well they emulate a particular target trial. We outline a framework for comparative effectiveness research using big data that makes the target trial explicit. This framework channels counterfactual theory for comparing the effects of sustained treatment strategies, organizes analytic approaches, provides a structured process for the criticism of observational studies, and helps avoid common methodologic pitfalls. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Is using multiple imputation better than complete case analysis for estimating a prevalence (risk) difference in randomized controlled trials when binary outcome observations are missing?

PubMed

Mukaka, Mavuto; White, Sarah A; Terlouw, Dianne J; Mwapasa, Victor; Kalilani-Phiri, Linda; Faragher, E Brian

2016-07-22

Missing outcomes can seriously impair the ability to make correct inferences from randomized controlled trials (RCTs). Complete case (CC) analysis is commonly used, but it reduces sample size and is perceived to lead to reduced statistical efficiency of estimates while increasing the potential for bias. As multiple imputation (MI) methods preserve sample size, they are generally viewed as the preferred analytical approach. We examined this assumption, comparing the performance of CC and MI methods to determine risk difference (RD) estimates in the presence of missing binary outcomes. We conducted simulation studies of 5000 simulated data sets with 50 imputations of RCTs with one primary follow-up endpoint at different underlying levels of RD (3-25 %) and missing outcomes (5-30 %). For missing at random (MAR) or missing completely at random (MCAR) outcomes, CC method estimates generally remained unbiased and achieved precision similar to or better than MI methods, and high statistical coverage. Missing not at random (MNAR) scenarios yielded invalid inferences with both methods. Effect size estimate bias was reduced in MI methods by always including group membership even if this was unrelated to missingness. Surprisingly, under MAR and MCAR conditions in the assessed scenarios, MI offered no statistical advantage over CC methods. While MI must inherently accompany CC methods for intention-to-treat analyses, these findings endorse CC methods for per protocol risk difference analyses in these conditions. These findings provide an argument for the use of the CC approach to always complement MI analyses, with the usual caveat that the validity of the mechanism for missingness be thoroughly discussed. More importantly, researchers should strive to collect as much data as possible.

[How to fit and interpret multilevel models using SPSS].

PubMed

Pardo, Antonio; Ruiz, Miguel A; San Martín, Rafael

2007-05-01

Hierarchic or multilevel models are used to analyse data when cases belong to known groups and sample units are selected both from the individual level and from the group level. In this work, the multilevel models most commonly discussed in the statistic literature are described, explaining how to fit these models using the SPSS program (any version as of the 11 th ) and how to interpret the outcomes of the analysis. Five particular models are described, fitted, and interpreted: (1) one-way analysis of variance with random effects, (2) regression analysis with means-as-outcomes, (3) one-way analysis of covariance with random effects, (4) regression analysis with random coefficients, and (5) regression analysis with means- and slopes-as-outcomes. All models are explained, trying to make them understandable to researchers in health and behaviour sciences.

Effects of Automobile Commute Characteristics on Affect and Job Candidate Evaluations: A Field Experiment

ERIC Educational Resources Information Center

Van Rooy, David L.

2006-01-01

The current study assesses the effects of the commuting environment on affective states and hiring decisions. A total of 136 undergraduate females were randomly assigned to one of four conditions based on the length (10 km vs. 30 km) and level of congestion (low vs. high) during a commute. Multivariate analyses of variance indicate that affective…

The Effects of Research-Based Curriculum Materials and Curriculum-Based Professional Development on High School Science Achievement: Results of a Cluster-Randomized Trial

ERIC Educational Resources Information Center

Taylor, Joseph; Kowalski, Susan; Getty, Stephen; Wilson, Christopher; Carlson, Janet

2013-01-01

Effective instructional materials can be valuable interventions to improve student interest and achievement in science (National Research Council [NRC], 2007); yet, analyses indicate that many science instructional materials and curricula are fragmented, lack coherence, and are not carefully articulated through a sequence of grade levels (AAAS,…

Moderating effect of intrinsic religiosity on the relationship between depression and cognitive function among community-dwelling older adults.

PubMed

Foong, Hui Foh; Hamid, Tengku Aizan; Ibrahim, Rahimah; Haron, Sharifah Azizah

2018-04-01

Research has found that depression in later life is associated with cognitive impairment. Thus, the mechanism to reduce the effect of depression on cognitive function is warranted. In this paper, we intend to examine whether intrinsic religiosity mediates the association between depression and cognitive function. The study included 2322 nationally representative community-dwelling elderly in Malaysia, randomly selected through a multi-stage proportional cluster random sampling from Peninsular Malaysia. The elderly were surveyed on socio-demographic information, cognitive function, depression and intrinsic religiosity. A four-step moderated hierarchical regression analysis was employed to test the moderating effect. Statistical analyses were performed using SPSS (version 15.0). Bivariate analyses showed that both depression and intrinsic religiosity had significant relationships with cognitive function. In addition, four-step moderated hierarchical regression analysis revealed that the intrinsic religiosity moderated the association between depression and cognitive function, after controlling for selected socio-demographic characteristics. Intrinsic religiosity might reduce the negative effect of depression on cognitive function. Professionals who are working with depressed older adults should seek ways to improve their intrinsic religiosity as one of the strategies to prevent cognitive impairment.

Random mechanics: Nonlinear vibrations, turbulences, seisms, swells, fatigue

NASA Astrophysics Data System (ADS)

Kree, P.; Soize, C.

The random modeling of physical phenomena, together with probabilistic methods for the numerical calculation of random mechanical forces, are analytically explored. Attention is given to theoretical examinations such as probabilistic concepts, linear filtering techniques, and trajectory statistics. Applications of the methods to structures experiencing atmospheric turbulence, the quantification of turbulence, and the dynamic responses of the structures are considered. A probabilistic approach is taken to study the effects of earthquakes on structures and to the forces exerted by ocean waves on marine structures. Theoretical analyses by means of vector spaces and stochastic modeling are reviewed, as are Markovian formulations of Gaussian processes and the definition of stochastic differential equations. Finally, random vibrations with a variable number of links and linear oscillators undergoing the square of Gaussian processes are investigated.

Effect of Green Tea on Plasma Adiponectin Levels: A Systematic Review and Meta-analysis of Randomized Controlled Clinical Trials.

PubMed

Haghighatdoost, Fahimeh; Nobakht M Gh, B Fatemeh; Hariri, Mitra

2017-01-01

Our objective was to perform a systematic review and meta-analysis on randomized controlled trials (RCTs) assessing the effect of green tea on serum adiponectin concentration. We searched PubMed, ISI Web of Science, Scopus, and the Google Scholar databases up to November 2016. RCTs conducted among human adults studied the effects of green tea and green tea extract on serum adiponectin concentrations as an outcome variable was included. The weighted mean differences and standard deviations (SD) of change in serum adiponectin levels were calculated. The random effects model was used for deriving a summary of mean estimates with their corresponding SDs. The protocol was registered with PROSPERO (No. CRD42017057716). Fourteen RCTs were eligible to be included in the systematic review and the meta-analysis. Our analysis showed that green tea did not significantly affect adiponectin concentrations in comparison with placebo (weighted mean difference = -0.02 µg/ml, 95% confidence interval [CI], -0.41, 0.38; p = 0.936). There was a substantial heterogeneity between studies (I 2 = 91.7%; p < 0.0001). Subgroup analyses based on sex, type of intervention, continent, and body mass index (BMI) could not explain the sources of heterogeneity. Metaregression analyses revealed that the dose and duration of green tea ingestion did not have any effect on adiponectin concentrations. Green tea could not change the circulatory adiponectin levels. The dose and duration of green tea could not change the result. RCTs with longer follow-up periods and higher doses are needed to replicate our results.

Effect of a medical food on body mass index and activities of daily living in patients with Alzheimer's disease: secondary analyses from a randomized, controlled trial.

PubMed

Kamphuis, P J G H; Verhey, F R J; Olde Rikkert, M G M; Twisk, J W R; Swinkels, S H N; Scheltens, P

2011-08-01

To investigate the effect of a medical food (Souvenaid) on body mass index (BMI) and functional abilities in patients with mild Alzheimer's disease (AD). DESIGN/SETTING/PARTICIPANTS/INTERVENTION /MEASUREMENTS: These analyses were performed on data from a 12-week, double-blind, randomized, controlled, multicenter, proof-of-concept study with a similarly designed and exploratory 12-week extension period. Patients with mild AD (Mini-Mental State Examination score of 20-26) were randomized to receive either the active product or an iso-caloric control product. While primary outcomes included measures of cognition, the 23-item Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale was included as a secondary outcome. Both ADCS-ADL and BMI were assessed at baseline and Weeks 6, 12 and 24. Data were analyzed using a repeated-measures mixed model. Overall, data suggested an increased BMI in the active versus the control group at Week 24 (ITT: p = 0.07; PP: p = 0.03), but no treatment effect on ADCS-ADL was observed. However, baseline BMI was found to be a significant treatment effect modifier (ITT: p = 0.04; PP: p = 0.05), and an increase in ADCS-ADL was observed at Week 12 in patients with a 'low' baseline BMI (ITT: p = 0.02; PP: p = 0.04). These data indicate that baseline BMI significantly impacts the effect of Souvenaid on functional abilities. In addition, there was a suggestion that Souvenaid increased BMI.

Recruitment techniques for alcohol pharmacotherapy clinical trials: A cost-benefit analysis

PubMed Central

Tompkins, D. Andrew; Sides, Jessica A.; Harrison, Joseph A.; Strain, Eric C.

2014-01-01

Objectives Alcohol use disorders (AUDs) represent a large public health burden with relatively few efficacious pharmacotherapies. Randomized controlled trials (RCTs) for new AUD therapies can be hampered by ineffective recruitment, leading to increased trial costs. The current analyses examined the effectiveness of recruitment efforts during two consecutive outpatient RCTs of novel AUD pharmacotherapies conducted between 2009 and 2012. Methods During an initial phone screen, participants identified an ad source for learning about the study. Qualified persons were then scheduled for in-person screens. The present analyses examined demographic differences amongst the eight ad sources utilized. Recruitment effectiveness was determined by dividing the number of persons meeting criteria for an in-person screen by the total number of callers from each ad source. Cost-effectiveness was determined by dividing total ad source cost by number of screens, participants randomized, and completers. Results 1,813 calls resulted in 1,005 completed phone screens. The most common ad source was TV (34%), followed by print (29%), word-of-mouth (11%), flyer (8%), internet (5%), radio (5%), bus ad (2%), and billboard (1%). Participants reporting bus ads (46%), billboard (44%), or print ads (34%) were significantly more likely than the other sources to meet criteria to be scheduled for in-person screens. The most cost-effective ad source was print ($2,506 per completer), while bus ad was the least cost-effective ($13,376 per completer). Conclusions Recruitment in AUD RCTs can be successful using diverse advertising methods. The present analyses favored use of print ads as most cost-effective. PMID:26752979

Using a genetic, observational study as a strategy to estimate the potential cost-effectiveness of pharmacological CCR5 blockade in dialysis patients.

PubMed

Muntinghe, Friso L H; Vegter, Stefan; Verduijn, Marion; Boeschoten, Elisabeth W; Dekker, Friedo W; Navis, Gerjan; Postma, Maarten

2011-07-01

Randomized clinical trials are expensive and time consuming. Therefore, strategies are needed to prioritise tracks for drug development. Genetic association studies may provide such a strategy by considering the differences between genotypes as a proxy for a natural, lifelong, randomized at conception, clinical trial. Previously an association with better survival was found in dialysis patients with systemic inflammation carrying a deletion variant of the CC-chemokine receptor 5 (CCR5). We hypothesized that in an analogous manner, pharmacological CCR5 blockade could protect against inflammation-driven mortality and estimated if such a treatment would be cost-effective. A genetic screen and treat strategy was modelled using a decision-analytic Markov model, in which patients were screened for the CCR5 deletion 32 polymorphism and those with the wild type and systemic inflammation were treated with pharmacological CCR5 blockers. Kidney transplantation and mortality rates were calculated using patient level data. Extensive sensitivity analyses were performed. The cost-effectiveness of the genetic screen and treat strategy was &OV0556;18 557 per life year gained and &OV0556;21 896 per quality-adjusted life years gained. Concordance between the genetic association and pharmacological effectiveness was a main driver of cost-effectiveness. Sensitivity analyses showed that even a modest effectiveness of pharmacological CCR5 blockade would result in a treatment strategy that is good value for money. Pharmacological blockade of the CCR5 receptor in inflamed dialysis patients can be incorporated in a potentially cost-effective screen and treat programme. These findings provide formal rationale for clinical studies. This study illustrates the potential of genetic association studies for drug development, as a source of Mendelian randomized evidence from an observational setting.

Effect of vitamin E supplementation on serum C-reactive protein level: a meta-analysis of randomized controlled trials.

PubMed

Saboori, S; Shab-Bidar, S; Speakman, J R; Yousefi Rad, E; Djafarian, K

2015-08-01

C-reactive protein (CRP), a marker of chronic inflammation, has a major role in the etiology of chronic disease. Vitamin E may have anti-inflammatory effects. However, there is no consensus on the effects of vitamin E supplementation on CRP levels in clinical trials. The aim of this study was to systematically review randomized controlled trials (RCTs) that report on the effects of vitamin E supplementation (α- and γ-tocopherols) on CRP levels. A systematic search of RCTs was conducted on Medline and EMBASE through PubMed, Scopus, Ovid and Science Direct, and completed by a manual review of the literature up to May 2014. Pooled effects were estimated by using random-effects models and heterogeneity was assessed by Cochran's Q and I(2) tests. Subgroup analyses and meta-regression analyses were also performed according to intervention duration, dose of supplementation and baseline level of CRP. Of 4734 potentially relevant studies, only 12 trials met the inclusion criteria with 246 participants in the intervention arms and 249 participants in control arms. Pooled analysis showed a significant reduction in CRP levels of 0.62 mg/l (95% confidence interval = -0.92, -0.31; P < 0.001) in vitamin E-treated individuals, with the evidence of heterogeneity across studies. This significant effect was maintained in all subgroups, although the univariate meta-regression analysis showed that the vitamin E supplementation dose, baseline level of CRP and duration of intervention were not the sources of the observed heterogeneity. The results of this meta-analysis suggest that supplementation with vitamin E in the form of either α-tocopherol or γ-tocopherol would reduce serum CRP levels.

Impact of food labelling systems on food choices and eating behaviours: a systematic review and meta-analysis of randomized studies.

PubMed

Cecchini, M; Warin, L

2016-03-01

Food labels are considered a crucial component of strategies tackling unhealthy diets and obesity. This study aims at assessing the effectiveness of food labelling in increasing the selection of healthier products and in reducing calorie intake. In addition, this study compares the relative effectiveness of traffic light schemes, Guideline Daily Amount and other food labelling schemes. A comprehensive set of databases were searched to identify randomized studies. Studies reporting homogeneous outcomes were pooled together and analysed through meta-analyses. Publication bias was evaluated with a funnel plot. Food labelling would increase the amount of people selecting a healthier food product by about 17.95% (confidence interval: +11.24% to +24.66%). Food labelling would also decrease calorie intake/choice by about 3.59% (confidence interval: -8.90% to +1.72%), but results are not statistically significant. Traffic light schemes are marginally more effective in increasing the selection of healthier options. Other food labels and Guideline Daily Amount follow. The available evidence did not allow studying the effects of single labelling schemes on calorie intake/choice. Findings of this study suggest that nutrition labelling may be an effective approach to empowering consumers in choosing healthier products. Interpretive labels, as traffic light labels, may be more effective. © 2015 World Obesity.

Do Bayesian adaptive trials offer advantages for comparative effectiveness research? Protocol for the RE-ADAPT study

PubMed Central

Luce, Bryan R; Broglio, Kristine R; Ishak, K Jack; Mullins, C Daniel; Vanness, David J; Fleurence, Rachael; Saunders, Elijah; Davis, Barry R

2013-01-01

Background Randomized clinical trials, particularly for comparative effectiveness research (CER), are frequently criticized for being overly restrictive or untimely for health-care decision making. Purpose Our prospectively designed REsearch in ADAptive methods for Pragmatic Trials (RE-ADAPT) study is a ‘proof of concept’ to stimulate investment in Bayesian adaptive designs for future CER trials. Methods We will assess whether Bayesian adaptive designs offer potential efficiencies in CER by simulating a re-execution of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study using actual data from ALLHAT. Results We prospectively define seven alternate designs consisting of various combinations of arm dropping, adaptive randomization, and early stopping and describe how these designs will be compared to the original ALLHAT design. We identify the one particular design that would have been executed, which incorporates early stopping and information-based adaptive randomization. Limitations While the simulation realistically emulates patient enrollment, interim analyses, and adaptive changes to design, it cannot incorporate key features like the involvement of data monitoring committee in making decisions about adaptive changes. Conclusion This article describes our analytic approach for RE-ADAPT. The next stage of the project is to conduct the re-execution analyses using the seven prespecified designs and the original ALLHAT data. PMID:23983160

Impact of a social-emotional and character development program on school-level indicators of academic achievement, absenteeism, and disciplinary outcomes: A matched-pair, cluster randomized, controlled trial.

PubMed

Snyder, Frank; Flay, Brian; Vuchinich, Samuel; Acock, Alan; Washburn, Isaac; Beets, Michael; Li, Kin-Kit

2010-01-01

This paper reports the effects of a comprehensive elementary school-based social-emotional and character education program on school-level achievement, absenteeism, and disciplinary outcomes utilizing a matched-pair, cluster randomized, controlled design. The Positive Action Hawai'i trial included 20 racially/ethnically diverse schools (mean enrollment = 544) and was conducted from the 2002-03 through the 2005-06 academic years. Using school-level archival data, analyses comparing change from baseline (2002) to one-year post trial (2007) revealed that intervention schools scored 9.8% better on the TerraNova (2 nd ed.) test for reading and 8.8% on math; 20.7% better in Hawai'i Content and Performance Standards scores for reading and 51.4% better in math; and that intervention schools reported 15.2% lower absenteeism and fewer suspensions (72.6%) and retentions (72.7%). Overall, effect sizes were moderate to large (range 0.5-1.1) for all of the examined outcomes. Sensitivity analyses using permutation models and random-intercept growth curve models substantiated results. The results provide evidence that a comprehensive school-based program, specifically developed to target student behavior and character, can positively influence school-level achievement, attendance, and disciplinary outcomes concurrently.

Systematic review and meta-analyses of randomized controlled trials examining tinnitus management

PubMed Central

Hoare, Derek J; Kowalkowski, Victoria L; Kang, Sujin; Hall, Deborah A

2011-01-01

Objectives/Hypothesis To evaluate the existing level of evidence for tinnitus management strategies identified in the UK Department of Health's Good Practice Guideline. Study Design Systematic review of peer-reviewed literature and meta-analyses. Methods Searches were conducted in PubMed, Cambridge Scientific Abstracts, Web of Science, and EMBASE (earliest to August 2010), supplemented by hand searches in October 2010. Only randomized controlled trials that used validated questionnaire measures of symptoms (i.e., measures of tinnitus distress, anxiety, depression) were included. Results Twenty-eight randomized controlled trials met our inclusion criteria, most of which provide moderate levels of evidence for the effects they reported. Levels of evidence were generally limited by the lack of blinding, lack of power calculations, and incomplete data reporting in these studies. Only studies examining cognitive behavioral therapy were numerous and similar enough to perform meta-analysis, from which the efficacy of cognitive behavioral therapy (moderate effect size) appears to be reasonably established. Antidepressants were the only drug class to show any evidence of potential benefit. Conclusions The efficacy of most interventions for tinnitus benefit remains to be demonstrated conclusively. In particular, high-level assessment of the benefit derived from those interventions most commonly used in practice, namely hearing aids, maskers, and tinnitus retraining therapy needs to be performed. PMID:21671234

Strategies for Improving Power in School-Randomized Studies of Professional Development.

PubMed

Kelcey, Ben; Phelps, Geoffrey

2013-12-01

Group-randomized designs are well suited for studies of professional development because they can accommodate programs that are delivered to intact groups (e.g., schools), the collaborative nature of professional development, and extant teacher/school assignments. Though group designs may be theoretically favorable, prior evidence has suggested that they may be challenging to conduct in professional development studies because well-powered designs will typically require large sample sizes or expect large effect sizes. Using teacher knowledge outcomes in mathematics, we investigated when and the extent to which there is evidence that covariance adjustment on a pretest, teacher certification, or demographic covariates can reduce the sample size necessary to achieve reasonable power. Our analyses drew on multilevel models and outcomes in five different content areas for over 4,000 teachers and 2,000 schools. Using these estimates, we assessed the minimum detectable effect sizes for several school-randomized designs with and without covariance adjustment. The analyses suggested that teachers' knowledge is substantially clustered within schools in each of the five content areas and that covariance adjustment for a pretest or, to a lesser extent, teacher certification, has the potential to transform designs that are unreasonably large for professional development studies into viable studies. © The Author(s) 2014.

Metabolic Profiling of Adiponectin Levels in Adults: Mendelian Randomization Analysis.

PubMed

Borges, Maria Carolina; Barros, Aluísio J D; Ferreira, Diana L Santos; Casas, Juan Pablo; Horta, Bernardo Lessa; Kivimaki, Mika; Kumari, Meena; Menon, Usha; Gaunt, Tom R; Ben-Shlomo, Yoav; Freitas, Deise F; Oliveira, Isabel O; Gentry-Maharaj, Aleksandra; Fourkala, Evangelia; Lawlor, Debbie A; Hingorani, Aroon D

2017-12-01

Adiponectin, a circulating adipocyte-derived protein, has insulin-sensitizing, anti-inflammatory, antiatherogenic, and cardiomyocyte-protective properties in animal models. However, the systemic effects of adiponectin in humans are unknown. Our aims were to define the metabolic profile associated with higher blood adiponectin concentration and investigate whether variation in adiponectin concentration affects the systemic metabolic profile. We applied multivariable regression in ≤5909 adults and Mendelian randomization (using cis -acting genetic variants in the vicinity of the adiponectin gene as instrumental variables) for analyzing the causal effect of adiponectin in the metabolic profile of ≤37 545 adults. Participants were largely European from 6 longitudinal studies and 1 genome-wide association consortium. In the multivariable regression analyses, higher circulating adiponectin was associated with higher high-density lipoprotein lipids and lower very-low-density lipoprotein lipids, glucose levels, branched-chain amino acids, and inflammatory markers. However, these findings were not supported by Mendelian randomization analyses for most metabolites. Findings were consistent between sexes and after excluding high-risk groups (defined by age and occurrence of previous cardiovascular event) and 1 study with admixed population. Our findings indicate that blood adiponectin concentration is more likely to be an epiphenomenon in the context of metabolic disease than a key determinant. © 2017 The Authors.

Longitudinal analysis of the strengths and difficulties questionnaire scores of the Millennium Cohort Study children in England using M-quantile random-effects regression.

PubMed

Tzavidis, Nikos; Salvati, Nicola; Schmid, Timo; Flouri, Eirini; Midouhas, Emily

2016-02-01

Multilevel modelling is a popular approach for longitudinal data analysis. Statistical models conventionally target a parameter at the centre of a distribution. However, when the distribution of the data is asymmetric, modelling other location parameters, e.g. percentiles, may be more informative. We present a new approach, M -quantile random-effects regression, for modelling multilevel data. The proposed method is used for modelling location parameters of the distribution of the strengths and difficulties questionnaire scores of children in England who participate in the Millennium Cohort Study. Quantile mixed models are also considered. The analyses offer insights to child psychologists about the differential effects of risk factors on children's outcomes.

A meta-analysis of anxiety symptom prevention with cognitive-behavioral interventions.

PubMed

Zalta, Alyson K

2011-06-01

This meta-analysis assessed efficacy of cognitive-behavioral interventions in preventing anxiety symptoms. A systematic review identified 15 independent pretest-posttest randomized or quasi-randomized efficacy trials for analysis. At posttest, intervention groups demonstrated significantly greater symptom reduction compared to control groups resulting in weighted mean effect sizes (Hedges' g) of 0.25 for general anxiety, 0.24 for disorder-specific symptoms, and 0.22 for depression after the removal of outliers. These effects appeared to diminish over 6- and 12-month follow-up. Exploratory moderator analyses indicated that individually administered media interventions were more effective than human-administered group interventions at preventing general anxiety and depression symptoms. Implications of current findings are discussed with attention to existing gaps in the literature.

Nonpharmacological interventions for ADHD: systematic review and meta-analyses of randomized controlled trials of dietary and psychological treatments.

PubMed

Sonuga-Barke, Edmund J S; Brandeis, Daniel; Cortese, Samuele; Daley, David; Ferrin, Maite; Holtmann, Martin; Stevenson, Jim; Danckaerts, Marina; van der Oord, Saskia; Döpfner, Manfred; Dittmann, Ralf W; Simonoff, Emily; Zuddas, Alessandro; Banaschewski, Tobias; Buitelaar, Jan; Coghill, David; Hollis, Chris; Konofal, Eric; Lecendreux, Michel; Wong, Ian C K; Sergeant, Joseph

2013-03-01

Nonpharmacological treatments are available for attention deficit hyperactivity disorder (ADHD), although their efficacy remains uncertain. The authors undertook meta-analyses of the efficacy of dietary (restricted elimination diets, artificial food color exclusions, and free fatty acid supplementation) and psychological (cognitive training, neurofeedback, and behavioral interventions) ADHD treatments. Using a common systematic search and a rigorous coding and data extraction strategy across domains, the authors searched electronic databases to identify published randomized controlled trials that involved individuals who were diagnosed with ADHD (or who met a validated cutoff on a recognized rating scale) and that included an ADHD outcome. Fifty-four of the 2,904 nonduplicate screened records were included in the analyses. Two different analyses were performed. When the outcome measure was based on ADHD assessments by raters closest to the therapeutic setting, all dietary (standardized mean differences=0.21-0.48) and psychological (standardized mean differences=0.40-0.64) treatments produced statistically significant effects. However, when the best probably blinded assessment was employed, effects remained significant for free fatty acid supplementation (standardized mean difference=0.16) and artificial food color exclusion (standardized mean difference=0.42) but were substantially attenuated to nonsignificant levels for other treatments. Free fatty acid supplementation produced small but significant reductions in ADHD symptoms even with probably blinded assessments, although the clinical significance of these effects remains to be determined. Artificial food color exclusion produced larger effects but often in individuals selected for food sensitivities. Better evidence for efficacy from blinded assessments is required for behavioral interventions, neurofeedback, cognitive training, and restricted elimination diets before they can be supported as treatments for core ADHD symptoms.

Anticoagulant vs. antiplatelet therapy in patients with cryptogenic stroke and patent foramen ovale: an individual participant data meta-analysis.

PubMed

Kent, David M; Dahabreh, Issa J; Ruthazer, Robin; Furlan, Anthony J; Weimar, Christian; Serena, Joaquín; Meier, Bernhard; Mattle, Heinrich P; Di Angelantonio, Emanuele; Paciaroni, Maurizio; Schuchlenz, Herwig; Homma, Shunichi; Lutz, Jennifer S; Thaler, David E

2015-09-14

The preferred antithrombotic strategy for secondary prevention in patients with cryptogenic stroke (CS) and patent foramen ovale (PFO) is unknown. We pooled multiple observational studies and used propensity score-based methods to estimate the comparative effectiveness of oral anticoagulation (OAC) compared with antiplatelet therapy (APT). Individual participant data from 12 databases of medically treated patients with CS and PFO were analysed with Cox regression models, to estimate database-specific hazard ratios (HRs) comparing OAC with APT, for both the primary composite outcome [recurrent stroke, transient ischaemic attack (TIA), or death] and stroke alone. Propensity scores were applied via inverse probability of treatment weighting to control for confounding. We synthesized database-specific HRs using random-effects meta-analysis models. This analysis included 2385 (OAC = 804 and APT = 1581) patients with 227 composite endpoints (stroke/TIA/death). The difference between OAC and APT was not statistically significant for the primary composite outcome [adjusted HR = 0.76, 95% confidence interval (CI) 0.52-1.12] or for the secondary outcome of stroke alone (adjusted HR = 0.75, 95% CI 0.44-1.27). Results were consistent in analyses applying alternative weighting schemes, with the exception that OAC had a statistically significant beneficial effect on the composite outcome in analyses standardized to the patient population who actually received APT (adjusted HR = 0.64, 95% CI 0.42-0.99). Subgroup analyses did not detect statistically significant heterogeneity of treatment effects across clinically important patient groups. We did not find a statistically significant difference comparing OAC with APT; our results justify randomized trials comparing different antithrombotic approaches in these patients. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

A multi-state model for sick-leave data applied to a randomized control trial study of low back pain.

PubMed

Lie, Stein Atle; Eriksen, Hege R; Ursin, Holger; Hagen, Eli Molde

2008-05-01

Analysing and presenting data on different outcomes after sick-leave is challenging. The use of extended statistical methods supplies additional information and allows further exploitation of data. Four hundred and fifty-seven patients, sick-listed for 8-12 weeks for low back pain, were randomized to intervention (n=237) or control (n=220). Outcome was measured as: "sick-listed'', "returned to work'', or "disability pension''. The individuals shifted between the three states between one and 22 times (mean 6.4 times). In a multi-state model, shifting between the states was set up in a transition intensity matrix. The probability of being in any of the states was calculated as a transition probability matrix. The effects of the intervention were modelled using a non-parametric model. There was an effect of the intervention for leaving the state sick-listed and shifting to returned to work (relative risk (RR)=1.27, 95% confidence interval (CI) 1.09- 1.47). The nonparametric estimates showed an effect of the intervention for leaving sick-listed and shifting to returned to work in the first 6 months. We found a protective effect of the intervention for shifting back to sick-listed between 6 and 18 months. The analyses showed that the probability of staying in the state returned to work was not different between the intervention and control groups at the end of the follow-up (3 years). We demonstrate that these alternative analyses give additional results and increase the strength of the analyses. The simple intervention did not decrease the probability of being on sick-leave in the long term; however, it decreased the time that individuals were on sick-leave.

A Randomized Trial Examining the Effects of Aerobic Physical Activity on Attention-Deficit/Hyperactivity Disorder Symptoms in Young Children

PubMed Central

Hoza, Betsy; Smith, Alan L.; Shoulberg, Erin K.; Linnea, Kate S.; Dorsch, Travis E.; Blazo, Jordan A.; Alerding, Caitlin M.; McCabe, George P.

2014-01-01

The goal of this study was to compare the effects of before school physical activity (PA) and sedentary classroom-based (SC) interventions on the symptoms, behavior, moodiness and peer functioning of young children (Mage = 6.83) at risk for attention-deficit/hyperactivity disorder (ADHD-risk; n = 94) and typically developing children (TD; n = 108). Children were randomly assigned to either PA or SC and participated in the assigned intervention 31 minutes per day, each school day, over the course of 12 weeks. Parent and teacher ratings of ADHD symptoms (inattention, hyperactivity/impulsivity), oppositional behavior, moodiness, behavior toward peers, and reputation with peers, were used as dependent variables. Primary analyses indicate that the PA intervention was more effective than the SC intervention at reducing inattention and moodiness in the home context. Less conservative follow-up analyses within ADHD status and intervention groups suggest that a PA intervention may reduce impairment associated with ADHD-risk in both home and school domains; interpretive caution is warranted, however, given the liberal approach to these analyses. Unexpectedly, these findings also indicate the potential utility of a before school SC intervention as a tool for managing ADHD symptoms. Inclusion of a no treatment control group in future studies will enable further understanding of PA as an alternative management strategy for ADHD symptoms. PMID:25201345

A randomized trial examining the effects of aerobic physical activity on attention-deficit/hyperactivity disorder symptoms in young children.

PubMed

Hoza, Betsy; Smith, Alan L; Shoulberg, Erin K; Linnea, Kate S; Dorsch, Travis E; Blazo, Jordan A; Alerding, Caitlin M; McCabe, George P

2015-05-01

The goal of this study was to compare the effects of before school physical activity (PA) and sedentary classroom-based (SC) interventions on the symptoms, behavior, moodiness, and peer functioning of young children (M age = 6.83) at risk for attention-deficit/hyperactivity disorder (ADHD-risk; n = 94) and typically developing children (TD; n = 108). Children were randomly assigned to either PA or SC and participated in the assigned intervention 31 min per day, each school day, over the course of 12 weeks. Parent and teacher ratings of ADHD symptoms (inattention, hyperactivity/impulsivity), oppositional behavior, moodiness, behavior toward peers, and reputation with peers, were used as dependent variables. Primary analyses indicate that the PA intervention was more effective than the SC intervention at reducing inattention and moodiness in the home context. Less conservative follow-up analyses within ADHD status and intervention groups suggest that a PA intervention may reduce impairment associated with ADHD-risk in both home and school domains; interpretive caution is warranted, however, given the liberal approach to these analyses. Unexpectedly, these findings also indicate the potential utility of a before school SC intervention as a tool for managing ADHD symptoms. Inclusion of a no treatment control group in future studies will enable further understanding of PA as an alternative management strategy for ADHD symptoms.

Open transinguinal preperitoneal mesh repair of inguinal hernia: a targeted systematic review and meta-analysis of published randomized controlled trials

PubMed Central

Sajid, Muhammad S.; Craciunas, L.; Singh, K.K.; Sains, P.; Baig, M.K.

2013-01-01

Objective: The objective of this article is to systematically analyse the randomized, controlled trials comparing transinguinal preperitoneal (TIPP) and Lichtenstein repair (LR) for inguinal hernia. Methods: Randomized, controlled trials comparing TIPP vs LR were analysed systematically using RevMan® and combined outcomes were expressed as risk ratio (RR) and standardized mean difference. Results: Twelve randomized trials evaluating 1437 patients were retrieved from the electronic databases. There were 714 patients in the TIPP repair group and 723 patients in the LR group. There was significant heterogeneity among trials (P < 0.0001). Therefore, in the random effects model, TIPP repair was associated with a reduced risk of developing chronic groin pain (RR, 0.48; 95% CI, 0.26, 0.89; z = 2.33; P < 0.02) without influencing the incidence of inguinal hernia recurrence (RR, 0.18; 95% CI, 0.36, 1.83; z = 0.51; P = 0.61). Risk of developing postoperative complications and moderate-to-severe postoperative pain was similar following TIPP repair and LR. In addition, duration of operation was statistically similar in both groups. Conclusion: TIPP repair for inguinal hernia is associated with lower risk of developing chronic groin pain. It is comparable with LR in terms of risk of hernia recurrence, postoperative complications, duration of operation and intensity of postoperative pain. PMID:24759818

Nurse practitioners can effectively deliver pain coping skills training to osteoarthritis patients with chronic pain: A randomized, controlled trial

PubMed Central

Broderick, Joan E.; Keefe, Francis J.; Bruckenthal, Patricia; Junghaenel, Doerte U.; Schneider, Stefan; Schwartz, Joseph E.; Kaell, Alan T.; Caldwell, David S.; McKee, Daphne; Reed, Shelby; Gould, Elaine

2014-01-01

A multisite, randomized, controlled clinical effectiveness trial was conducted for osteoarthritis patients with chronic pain of the knee or hip. Adult health nurse practitioners provided a 10-session intervention, pain coping skills training (PCST), in patients’ doctors’ offices (N = 129 patients); the control group received usual care (N = 127 patients). Primary outcomes assessed at baseline, posttreatment, 6-month follow-up, and 12-month follow-up were: pain intensity, physical functioning, psychological distress, self-efficacy, catastrophizing, use of coping strategies, and quality of life. Secondary measures included fatigue, social functioning, health satisfaction, and use of pain medication. Methods favoring external validity, consistent with pragmatic, effectiveness research, were utilized. Primary ITT and secondary per-protocol analyses were conducted. Attrition was within the expected range: 11% at posttreatment and 29% at 12-month follow-up; rates did not differ between groups. Omnibus ITT analyses across all assessment points indicated significant improvement for the PCST group compared with the control group for pain intensity, physical functioning, psychological distress, use of pain coping strategies, and self-efficacy, as well as fatigue, satisfaction with health, and reduced use of pain medication. Treatment effects were robust to covariates (demographics and clinical sites). Trends in the outcomes across the assessments were examined. All outcomes, except for self-efficacy, were maintained through the 12-month follow-up; effects for self-efficacy degraded over time. Per-protocol analyses did not yield greater effect sizes. Comparisons of PCST patients who were more vs less treatment adherent suggested greater effectiveness for patients with high adherence. Results support the effectiveness of nurse practitioner delivery of PCST for chronic osteoarthritis pain. PMID:24865795

The Effects of Vortioxetine on Cognitive Function in Patients with Major Depressive Disorder: A Meta-Analysis of Three Randomized Controlled Trials

PubMed Central

Harrison, J; Loft, H; Jacobson, W; Olsen, CK

2016-01-01

Background: Management of cognitive deficits in Major Depressive Disorder (MDD) remains an important unmet need. This meta-analysis evaluated the effects of vortioxetine on cognition in patients with MDD. Methods: Random effects meta-analysis was applied to three randomized, double-blind, placebo-controlled 8-week trials of vortioxetine (5–20mg/day) in MDD, and separately to two duloxetine-referenced trials. The primary outcome measure was change in Digit Symbol Substitution Test (DSST) score. Standardized effect sizes (SES) versus placebo (Cohen’s d) were used as input. Path analysis was employed to determine the extent to which changes in DSST were mediated independently of a change in Montgomery-Åsberg Depression Rating Scale (MADRS) score. Meta-analysis was applied to MADRS-adjusted and -unadjusted SES values. Changes on additional cognitive tests were evaluated (source studies only). Results: Before adjustment for MADRS, vortioxetine separated from placebo on DSST score (SES 0.25–0.48; nominal p < 0.05) in all individual trials, and statistically improved DSST performance versus placebo in meta-analyses of the three trials (SES = 0.35; p < 0.0001) and two duloxetine-referenced trials (SES = 0.26; p = 0.001). After adjustment for MADRS, vortioxetine maintained DSST improvement in one individual trial (p = 0.001) and separation from placebo was maintained in meta-analyses of all three trials (SES = 0.24; p < 0.0001) and both duloxetine-referenced trials (SES 0.19; p = 0.01). Change in DSST with duloxetine failed to separate from placebo in individual trials and both meta-analyses. Change in DSST statistically favored vortioxetine versus duloxetine after MADRS adjustment (SES = 0.16; p = 0.04). Conclusions: Vortioxetine, but not duloxetine, significantly improved cognition, independent of depressive symptoms. Vortioxetine represents an important treatment for MDD-related cognitive dysfunction. PMID:27312740

An Exploratory Analysis of the Smoking and Physical Activity Outcomes From a Pilot Randomized Controlled Trial of an Exercise Assisted Reduction to Stop Smoking Intervention in Disadvantaged Groups.

PubMed

Thompson, Tom Paul; Greaves, Colin J; Ayres, Richard; Aveyard, Paul; Warren, Fiona C; Byng, Richard; Taylor, Rod S; Campbell, John L; Ussher, Michael; Green, Colin; Michie, Susan; West, Robert; Taylor, Adrian

2016-03-01

Economically disadvantaged smokers not intending to stop may benefit from interventions aimed at reducing their smoking. This study assessed the effects of a behavioral intervention promoting an increase in physical activity versus usual care in a pilot randomized controlled trial. Disadvantaged smokers who wanted to reduce but not quit were randomized to either a counseling intervention of up to 12 weeks to support smoking reduction and increased physical activity (n = 49) or usual care (n = 50). Data at 16 weeks were collected for various smoking and physical activity outcomes. Primary analyses consisted of an intention to treat analysis based on complete case data. Secondary analyses explored the impact of handling missing data. Compared with controls, intervention smokers were more likely to initiate a quit attempt (36 vs. 10%; odds ratio 5.05, [95% CI: 1.10; 23.15]), and a greater proportion achieved at least 50% reduction in cigarettes smoked (63 vs. 32%; 4.21 [1.32; 13.39]). Postquit abstinence measured by exhaled carbon monoxide at 4-week follow-up showed promising differences between groups (23% vs. 6%; 4.91 [0.80; 30.24]). No benefit of intervention on physical activity was found. Secondary analyses suggested that the standard missing data assumption of "missing" being equivalent to "smoking" may be conservative resulting in a reduced intervention effect. A smoking reduction intervention for economically disadvantaged smokers which involved personal support to increase physical activity appears to be more effective than usual care in achieving reduction and may promote cessation. The effect does not appear to be influenced by an increase in physical activity. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The effect of English-language restriction on systematic review-based meta-analyses: a systematic review of empirical studies.

PubMed

Morrison, Andra; Polisena, Julie; Husereau, Don; Moulton, Kristen; Clark, Michelle; Fiander, Michelle; Mierzwinski-Urban, Monika; Clifford, Tammy; Hutton, Brian; Rabb, Danielle

2012-04-01

The English language is generally perceived to be the universal language of science. However, the exclusive reliance on English-language studies may not represent all of the evidence. Excluding languages other than English (LOE) may introduce a language bias and lead to erroneous conclusions. We conducted a comprehensive literature search using bibliographic databases and grey literature sources. Studies were eligible for inclusion if they measured the effect of excluding randomized controlled trials (RCTs) reported in LOE from systematic review-based meta-analyses (SR/MA) for one or more outcomes. None of the included studies found major differences between summary treatment effects in English-language restricted meta-analyses and LOE-inclusive meta-analyses. Findings differed about the methodological and reporting quality of trials reported in LOE. The precision of pooled estimates improved with the inclusion of LOE trials. Overall, we found no evidence of a systematic bias from the use of language restrictions in systematic review-based meta-analyses in conventional medicine. Further research is needed to determine the impact of language restriction on systematic reviews in particular fields of medicine.

Effect of tree nuts on glycemic control in diabetes: a systematic review and meta-analysis of randomized controlled dietary trials.

PubMed

Viguiliouk, Effie; Kendall, Cyril W C; Blanco Mejia, Sonia; Cozma, Adrian I; Ha, Vanessa; Mirrahimi, Arash; Jayalath, Viranda H; Augustin, Livia S A; Chiavaroli, Laura; Leiter, Lawrence A; de Souza, Russell J; Jenkins, David J A; Sievenpiper, John L

2014-01-01

Tree nut consumption has been associated with reduced diabetes risk, however, results from randomized trials on glycemic control have been inconsistent. To provide better evidence for diabetes guidelines development, we conducted a systematic review and meta-analysis of randomized controlled trials to assess the effects of tree nuts on markers of glycemic control in individuals with diabetes. MEDLINE, EMBASE, CINAHL, and Cochrane databases through 6 April 2014. Randomized controlled trials ≥3 weeks conducted in individuals with diabetes that compare the effect of diets emphasizing tree nuts to isocaloric diets without tree nuts on HbA1c, fasting glucose, fasting insulin, and HOMA-IR. Two independent reviewer's extracted relevant data and assessed study quality and risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences (MD) with 95% CI's. Heterogeneity was assessed (Cochran Q-statistic) and quantified (I2). Twelve trials (n = 450) were included. Diets emphasizing tree nuts at a median dose of 56 g/d significantly lowered HbA1c (MD = -0.07% [95% CI:-0.10, -0.03%]; P = 0.0003) and fasting glucose (MD = -0.15 mmol/L [95% CI: -0.27, -0.02 mmol/L]; P = 0.03) compared with control diets. No significant treatment effects were observed for fasting insulin and HOMA-IR, however the direction of effect favoured tree nuts. Majority of trials were of short duration and poor quality. Pooled analyses show that tree nuts improve glycemic control in individuals with type 2 diabetes, supporting their inclusion in a healthy diet. Owing to the uncertainties in our analyses there is a need for longer, higher quality trials with a focus on using nuts to displace high-glycemic index carbohydrates. ClinicalTrials.gov NCT01630980.

Effect of Tree Nuts on Glycemic Control in Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Dietary Trials

PubMed Central

Viguiliouk, Effie; Kendall, Cyril W. C.; Blanco Mejia, Sonia; Cozma, Adrian I.; Ha, Vanessa; Mirrahimi, Arash; Jayalath, Viranda H.; Augustin, Livia S. A.; Chiavaroli, Laura; Leiter, Lawrence A.; de Souza, Russell J.; Jenkins, David J. A.; Sievenpiper, John L.

2014-01-01

Background Tree nut consumption has been associated with reduced diabetes risk, however, results from randomized trials on glycemic control have been inconsistent. Objective To provide better evidence for diabetes guidelines development, we conducted a systematic review and meta-analysis of randomized controlled trials to assess the effects of tree nuts on markers of glycemic control in individuals with diabetes. Data Sources MEDLINE, EMBASE, CINAHL, and Cochrane databases through 6 April 2014. Study Selection Randomized controlled trials ≥3 weeks conducted in individuals with diabetes that compare the effect of diets emphasizing tree nuts to isocaloric diets without tree nuts on HbA1c, fasting glucose, fasting insulin, and HOMA-IR. Data Extraction and Synthesis Two independent reviewer’s extracted relevant data and assessed study quality and risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences (MD) with 95% CI’s. Heterogeneity was assessed (Cochran Q-statistic) and quantified (I2). Results Twelve trials (n = 450) were included. Diets emphasizing tree nuts at a median dose of 56 g/d significantly lowered HbA1c (MD = −0.07% [95% CI:−0.10, −0.03%]; P = 0.0003) and fasting glucose (MD = −0.15 mmol/L [95% CI: −0.27, −0.02 mmol/L]; P = 0.03) compared with control diets. No significant treatment effects were observed for fasting insulin and HOMA-IR, however the direction of effect favoured tree nuts. Limitations Majority of trials were of short duration and poor quality. Conclusions Pooled analyses show that tree nuts improve glycemic control in individuals with type 2 diabetes, supporting their inclusion in a healthy diet. Owing to the uncertainties in our analyses there is a need for longer, higher quality trials with a focus on using nuts to displace high-glycemic index carbohydrates. Trial Registration ClinicalTrials.gov NCT01630980 PMID:25076495

Using structural equation modeling for network meta-analysis.

PubMed

Tu, Yu-Kang; Wu, Yun-Chun

2017-07-14

Network meta-analysis overcomes the limitations of traditional pair-wise meta-analysis by incorporating all available evidence into a general statistical framework for simultaneous comparisons of several treatments. Currently, network meta-analyses are undertaken either within the Bayesian hierarchical linear models or frequentist generalized linear mixed models. Structural equation modeling (SEM) is a statistical method originally developed for modeling causal relations among observed and latent variables. As random effect is explicitly modeled as a latent variable in SEM, it is very flexible for analysts to specify complex random effect structure and to make linear and nonlinear constraints on parameters. The aim of this article is to show how to undertake a network meta-analysis within the statistical framework of SEM. We used an example dataset to demonstrate the standard fixed and random effect network meta-analysis models can be easily implemented in SEM. It contains results of 26 studies that directly compared three treatment groups A, B and C for prevention of first bleeding in patients with liver cirrhosis. We also showed that a new approach to network meta-analysis based on the technique of unrestricted weighted least squares (UWLS) method can also be undertaken using SEM. For both the fixed and random effect network meta-analysis, SEM yielded similar coefficients and confidence intervals to those reported in the previous literature. The point estimates of two UWLS models were identical to those in the fixed effect model but the confidence intervals were greater. This is consistent with results from the traditional pairwise meta-analyses. Comparing to UWLS model with common variance adjusted factor, UWLS model with unique variance adjusted factor has greater confidence intervals when the heterogeneity was larger in the pairwise comparison. The UWLS model with unique variance adjusted factor reflects the difference in heterogeneity within each comparison. SEM provides a very flexible framework for univariate and multivariate meta-analysis, and its potential as a powerful tool for advanced meta-analysis is still to be explored.

Reconciling the effects of screening on prostate cancer mortality in the ERSPC and PLCO trials

PubMed Central

Tsodikov, Alex; Gulati, Roman; Heijnsdijk, Eveline AM; Pinsky, Paul F; Moss, Sue M; Qiu, Sheng; de Carvalho, Tiago M; Hugosson, Jonas; Berg, Christine D; Auvinen, Anssi; Andriole, Gerald L; Roobol, Monique J; Crawford, E David; Nelen, Vera; Kwiatkowski, Maciej; Zappa, Marco; Luján, Marcos; Villers, Arnauld; Feuer, Eric J; de Koning, Harry J; Mariotto, Angela B; Etzioni, Ruth

2017-01-01

Background The European Randomized Study of Screening for Prostate Cancer (ERSPC) found screening reduced prostate cancer (PC) mortality, but the Prostate, Lung, Colorectal, and Ovarian trial (PLCO) found no reduction. Objective To evaluate whether effects of screening on PC mortality relative to no screening differed between the ERSPC and PLCO. Design Cox regression of PC death in each trial arm adjusted for age and trial, and extended analyses that accounted for increased incidence due to screening and diagnostic workup on each arm via mean lead times (MLTs). MLTs were estimated empirically and using analytic or microsimulation models. Setting Randomized controlled trials in Europe and the US. Participants Men aged 55–69 (ERSPC) or 55–74 (PLCO) at randomization. Intervention Prostate cancer screening. Measurements PC incidence and survival from randomization; PC incidence in the US before screening began. Results Estimated MLTs were similar in the ERSPC and PLCO intervention arms but were longer in the PLCO control arm than the ERSPC control arm. Extended analyses found no evidence that effects of screening differed between trials (P=0.37–0.47, range across MLT estimation approaches) but strong evidence that benefit increased with MLT (P=0.0027–0.0032). Screening was estimated to confer a 7–9% reduction in PC death per year of MLT. This translated into an estimated 25–31% and 27–32% lower risk of PC death under screening as performed in the ERSPC and PLCO intervention arms, respectively, relative to no screening. Limitations MLT is a simple metric of screening and diagnostic workup. Conclusion After accounting for differences in implementation and settings, the ERSPC and PLCO provide compatible evidence that screening reduces PC mortality. PMID:28869989

Association between non-steroidal anti-inflammatory drug use and melanoma risk: a meta-analysis of 13 studies.

PubMed

Li, Shan; Liu, Yanqiong; Zeng, Zhiyu; Peng, Qiliu; Li, Ruolin; Xie, Li; Qin, Xue; Zhao, Jinmin

2013-08-01

Results of the association between non-steroidal anti-inflammatory drugs (NSAIDs) and melanoma risk have been inconsistent. We performed a meta-analysis of relevant studies to investigate the hypothesis of an association between NSAID use and melanoma risk. Systematic searches of the PubMed and several other databases up to 23 March 2013 were retrieved. All epidemiologic studies regarding NSAIDs and melanoma risk were included. Fixed- or random-effects meta-analytical models were used to calculate relative risk (RR) and corresponding 95 % confidence intervals (CIs). Sensitivity analyses, Galbraith plots, and subgroup analyses were also performed. Six case-control studies including 93,432 melanoma cases and 401,251 controls, six cohort studies consisting of 563,380 subjects, and one randomized controlled trial encompassing 39,876 participants were included in this analysis. Compared to non-use, ever use of any NSAIDs was not statistically significantly associated with melanoma risk based on the random-effects models (RR = 0.97, 95 % CI = 0.90-10.4, p = 0.401). No differences were found in the effects on melanoma risk of aspirin, non-aspirin NSAIDs, and cyclooxygenase-2 inhibitor use overall and stratified by gender. However, a slight reduction in the risk of melanoma by taking aspirin was observed in case-control studies (RR = 0.88, 95 % CI = 0.80-0.96, p = 0.004). Findings from this pooled analysis do not support the hypothesis that NSAID use provides potential benefits in preventing melanoma. More and larger randomized trials, including adequate numbers of patients, are required to further evaluate the relationship between NSAID use and melanoma.

A phase III randomized trial of gantenerumab in prodromal Alzheimer's disease.

PubMed

Ostrowitzki, Susanne; Lasser, Robert A; Dorflinger, Ernest; Scheltens, Philip; Barkhof, Frederik; Nikolcheva, Tania; Ashford, Elizabeth; Retout, Sylvie; Hofmann, Carsten; Delmar, Paul; Klein, Gregory; Andjelkovic, Mirjana; Dubois, Bruno; Boada, Mercè; Blennow, Kaj; Santarelli, Luca; Fontoura, Paulo

2017-12-08

Gantenerumab is a fully human monoclonal antibody that binds aggregated amyloid-β (Aβ) and removes Aβ plaques by Fc receptor-mediated phagocytosis. In the SCarlet RoAD trial, we assessed the efficacy and safety of gantenerumab in prodromal Alzheimer's disease (AD). In this randomized, double-blind, placebo-controlled phase III study, we investigated gantenerumab over 2 years. Patients were randomized to gantenerumab 105 mg or 225 mg or placebo every 4 weeks by subcutaneous injection. The primary endpoint was the change from baseline to week 104 in Clinical Dementia Rating Sum of Boxes (CDR-SB) score. We evaluated treatment effects on cerebrospinal fluid biomarkers (all patients) and amyloid positron emission tomography (substudy). A futility analysis was performed once 50% of patients completed 2 years of treatment. Safety was assessed in patients who received at least one dose. Of the 3089 patients screened, 797 were randomized. The study was halted early for futility; dosing was discontinued; and the study was unblinded. No differences between groups in the primary (least squares mean [95% CI] CDR-SB change from baseline 1.60 [1.28, 1.91], 1.69 [1.37, 2.01], and 1.73 [1.42, 2.04] for placebo, gantenerumab 105 mg, and gantenerumab 225 mg, respectively) or secondary clinical endpoints were observed. The incidence of generally asymptomatic amyloid-related imaging abnormalities increased in a dose- and APOE ε4 genotype-dependent manner. Exploratory analyses suggested a dose-dependent drug effect on clinical and biomarker endpoints. The study was stopped early for futility, but dose-dependent effects observed in exploratory analyses on select clinical and biomarker endpoints suggest that higher dosing with gantenerumab may be necessary to achieve clinical efficacy. ClinicalTrials.gov, NCT01224106 . Registered on October 14, 2010.

Protocol for the MATCH study (Mindfulness and Tai Chi for cancer health): A preference-based multi-site randomized comparative effectiveness trial (CET) of Mindfulness-Based Cancer Recovery (MBCR) vs. Tai Chi/Qigong (TCQ) for cancer survivors.

PubMed

Carlson, Linda E; Zelinski, Erin L; Speca, Michael; Balneaves, Lynda G; Jones, Jennifer M; Santa Mina, Daniel; Wayne, Peter M; Campbell, Tavis S; Giese-Davis, Janine; Faris, Peter; Zwicker, Jennifer; Patel, Kamala; Beattie, Tara L; Cole, Steve; Toivonen, Kirsti; Nation, Jill; Peng, Philip; Thong, Bruce; Wong, Raimond; Vohra, Sunita

2017-08-01

A growing number of cancer survivors suffer high levels of distress, depression and stress, as well as sleep disturbance, pain and fatigue. Two different mind-body interventions helpful for treating these problems are Mindfulness-Based Cancer Recovery (MBCR) and Tai Chi/Qigong (TCQ). However, while both interventions show efficacy compared to usual care, they have never been evaluated in the same study or directly compared. This study will be the first to incorporate innovative design features including patient choice while evaluating two interventions to treat distressed cancer survivors. It will also allow for secondary analyses of which program best targets specific symptoms in particular groups of survivors, based on preferences and baseline characteristics. The design is a preference-based multi-site randomized comparative effectiveness trial. Participants (N=600) with a preference for either MBCR or TCQ will receive their preferred intervention; while those without a preference will be randomized into either intervention. Further, within the preference and non-preference groups, participants will be randomized into immediate intervention or wait-list control. Total mood disturbance on the Profile of mood states (POMS) post-intervention is the primary outcome. Other measures taken pre- and post-intervention and at 6-month follow-up include quality of life, psychological functioning, cancer-related symptoms and physical functioning. Exploratory analyses investigate biomarkers (cortisol, cytokines, blood pressure/Heart Rate Variability, telomere length, gene expression), which may uncover potentially important effects on key biological regulatory and antineoplastic functions. Health economic measures will determine potential savings to the health system. Copyright © 2017 Elsevier Inc. All rights reserved.

Post Hoc Analyses of Randomized Clinical Trial for the Effect of Clopidogrel Added to Aspirin on Kidney Function.

PubMed

Ikeme, Jesse C; Pergola, Pablo E; Scherzer, Rebecca; Shlipak, Michael G; Benavente, Oscar R; Peralta, Carmen A

2017-07-07

Despite the high burden of CKD, few specific therapies are available that can halt disease progression. In animal models, clopidogrel has emerged as a potential therapy to preserve kidney function. The effect of clopidogrel on kidney function in humans has not been established. The Secondary Prevention of Small Subcortical Strokes Study randomized participants with prior lacunar stroke to treatment with aspirin or aspirin plus clopidogrel. We compared annual eGFR decline and incidence of rapid eGFR decline (≥30% from baseline) using generalized estimating equations and interval-censored proportional hazards regression, respectively. We also stratified our analyses by baseline eGFR, systolic BP target, and time after randomization. At randomization, median age was 62 (interquartile range, 55-71) years old; 36% had a history of diabetes, 90% had hypertension, and the median eGFR was 81 (interquartile range, 65-94) ml/min per 1 m 2 . Persons receiving aspirin plus clopidogrel had an average annual change in kidney function of -1.39 (95% confidence interval, -1.15 to -1.62) ml/min per 1.73 m 2 per year compared with -1.52 (95% confidence interval, -1.30 to -1.74) ml/min per 1.73 m 2 per year among persons receiving aspirin only ( P =0.42). Rapid kidney function decline occurred in 21% of participants receiving clopidogrel plus aspirin compared with 22% of participants receiving aspirin plus placebo (hazard ratio, 0.94; 95% confidence interval, 0.79 to 1.10; P =0.42). Findings did not vary by baseline eGFR, time after randomization, or systolic BP target (all P values for interaction were >0.3). We found no effect of clopidogrel added to aspirin compared with aspirin alone on kidney function decline among persons with prior lacunar stroke. Copyright © 2017 by the American Society of Nephrology.

Occupational exposure to polychlorinated biphenyls and risk of cutaneous melanoma: a meta-analysis.

PubMed

Boffetta, Paolo; Catalani, Simona; Tomasi, Cesare; Pira, Enrico; Apostoli, Pietro

2018-01-01

The aim of this study was to carry out a meta-analysis of studies on exposure to polychlorinated biphenyls (PCBs) and the risk of malignant melanoma (MM). We searched Scopus, PubMed, and reference lists; among 807 potentially relevant articles, we selected those based on 12 populations. Data were extracted according to a standardized form; the Newcastle-Ottawa Scale was used to assess study quality. Meta-analyses were carried out according to fixed-effect and random-effects models. The fixed-effect summary relative risk (RR) for MM was 0.91 [95% confidence interval (CI): 0.82-1.00]; the random-effects summary RR was 1.05 (95% CI: 0.78-1.32). The random-effects summary RR from eight occupational cohorts was 1.13 (95% CI: 0.91-1.35) and that from four community-based studies was 0.84 (95% CI: 0.36-1.31). The quality of the studies and the methods for PCB exposure assessment did not influence the RR. These results do not support the hypothesis of an association between PCB exposure and the risk of MM.

Methods for calculating confidence and credible intervals for the residual between-study variance in random effects meta-regression models

PubMed Central

2014-01-01

Background Meta-regression is becoming increasingly used to model study level covariate effects. However this type of statistical analysis presents many difficulties and challenges. Here two methods for calculating confidence intervals for the magnitude of the residual between-study variance in random effects meta-regression models are developed. A further suggestion for calculating credible intervals using informative prior distributions for the residual between-study variance is presented. Methods Two recently proposed and, under the assumptions of the random effects model, exact methods for constructing confidence intervals for the between-study variance in random effects meta-analyses are extended to the meta-regression setting. The use of Generalised Cochran heterogeneity statistics is extended to the meta-regression setting and a Newton-Raphson procedure is developed to implement the Q profile method for meta-analysis and meta-regression. WinBUGS is used to implement informative priors for the residual between-study variance in the context of Bayesian meta-regressions. Results Results are obtained for two contrasting examples, where the first example involves a binary covariate and the second involves a continuous covariate. Intervals for the residual between-study variance are wide for both examples. Conclusions Statistical methods, and R computer software, are available to compute exact confidence intervals for the residual between-study variance under the random effects model for meta-regression. These frequentist methods are almost as easily implemented as their established counterparts for meta-analysis. Bayesian meta-regressions are also easily performed by analysts who are comfortable using WinBUGS. Estimates of the residual between-study variance in random effects meta-regressions should be routinely reported and accompanied by some measure of their uncertainty. Confidence and/or credible intervals are well-suited to this purpose. PMID:25196829

Gender-specific Differences in Recurrence of Non-muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis.

PubMed

Uhlig, Annemarie; Strauss, Arne; Seif Amir Hosseini, Ali; Lotz, Joachim; Trojan, Lutz; Schmid, Marianne; Uhlig, Johannes

2017-09-06

The incidence of urothelial carcinoma of the bladder (UCB) is lower in women; however, women tend to present with more advanced disease. To date, there is no quantitative synthesis of studies reporting gender-specific outcomes in non-muscle-invasive UCB. To conduct a meta-analysis evaluating gender-specific differences in recurrence of non-muscle-invasive urinary bladder cancer (NMIBC). An unrestricted systematic literature search of the MEDLINE, EMBASE, and Cochrane libraries was conducted. Studies evaluating the impact of gender on disease recurrence after local treatment of NMIBC using multivariable Cox proportional hazard models were included. Random effect meta-analysis, subgroup analyses, meta-influence, and cumulative meta-analyses were conducted. Publication bias was assessed via a funnel plot and Eggeŕs test. Of 609 studies screened, 27 comprising 23 754 patients were included. Random effect meta-analyses indicated women at increased risk for UCB recurrence compared with men (hazard ratio [HR]=1.11, 95% confidence interval [CI]: 1.01-1.23, p=0.03). Subgroup analyses yielded estimates between HR=0.99 and HR=1.68. Gender-specific differences in UCB recurrence were most pronounced in studies administering exclusively bacillus Calmette-Guerin (BCG; HR=1.64, 95% CI: 1.13-2.39, p=0.01), especially in a long-term treatment regimen (HR=1.68, 95% CI: 1.32-2.15, p<0.001). Sensitivity analyses confirmed female patients at increased risk for UCB recurrence. Women are at increased risk for disease recurrence after local treatment of NMIBC compared with male patients. Reduced effectiveness of BCG treatment might underlie this observation. Gender-specific differences were evident across various subgroups and proved robust upon sensitivity analyses. In this report, we combined several studies on gender-specific differences in relapse of superficial bladder cancer. Women were more likely to experience cancer relapse than men. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Suicide and Firearm Means Restriction: Can Training Make a Difference?

ERIC Educational Resources Information Center

Slovak, Karen; Brewer, Thomas W.

2010-01-01

Along with physician education in depression recognition and treatment, restricting lethal methods is an effective suicide prevention strategy. The present study surveyed a random sample (N = 697) of Ohio licensed social workers regarding client firearm assessment and safety counseling. Analyses sought to determine what independent factors would…

A Retrospective Look at Website Accessibility over Time

ERIC Educational Resources Information Center

Hackett, Stephanie; Parmanto, Bambang; Zeng, Xiaoming

2005-01-01

Websites were retrospectively analysed to study the effects that technological advances in web design have had on accessibility for persons with disabilities. A random sample of general websites and a convenience sample of US government websites were studied and compared for the years 1997-2002. Web accessibility barrier (WAB) and complexity…

Comparative evidence on harms in pediatric randomized clinical trials from less developed versus more developed countries is limited.

PubMed

Tedesco, Dario; Farid-Kapadia, Mufiza; Offringa, Martin; Bhutta, Zulfiqar A; Maldonado, Yvonne; Ioannidis, John P A; Contopoulos-Ioannidis, Despina G

2018-03-01

Evaluate comparative harm rates from medical interventions in pediatric randomized clinical trials (RCTs) from more developed (MDCs) and less developed countries (LDCs). Meta-epidemiologic empirical evaluation of Cochrane Database of Systematic Reviews (June 2014) meta-analyses reporting clinically important harm-outcomes (severe adverse events [AEs], discontinuations due to AEs, any AE, and mortality) that included at least one pediatric RCT from MDCs and at least one from LDCs. We estimated relative odds ratios (RORs) for each harm, within each meta-analysis, between RCTs from MDCs and LDCs and calculated random-effects-summary-RORs (sRORs) for each harm across multiple meta-analyses. Only 1% (26/2,363) of meta-analyses with clinically important harm-outcomes in the entire Cochrane Database of Systematic Reviews included pediatric RCTs both from MDCs and LDCs. We analyzed 26 meta-analyses with 244 data sets from pediatric RCTs, 116 from MDCs and 128 from LDCs (64 and 66 unique RCTs respectively). The summary ROR was 0.92 (95% confidence intervals: 0.78-1.08) for severe AEs; 1.13 (0.54-2.34) for discontinuations due to AEs; 1.10 (0.77-1.59) for any AE; and 0.99 (0.61-1.61) for mortality and for the all-harms-combined-end point 0.96 (0.83-1.10). Differences of ROR-point-estimates ≥2-fold between MDCs and LDCs were identified in 35% of meta-analyses. We found no major systematic differences in harm rates in pediatric trials between MDCs and LDCs, but data on harms in children were overall very limited. Copyright © 2017 Elsevier Inc. All rights reserved.

Local Anesthetic Peripheral Nerve Block Adjuvants for Prolongation of Analgesia: A Systematic Qualitative Review

PubMed Central

Kirksey, Meghan A.; Haskins, Stephen C.; Cheng, Jennifer; Liu, Spencer S.

2015-01-01

Background The use of peripheral nerve blocks for anesthesia and postoperative analgesia has increased significantly in recent years. Adjuvants are frequently added to local anesthetics to prolong analgesia following peripheral nerve blockade. Numerous randomized controlled trials and meta-analyses have examined the pros and cons of the use of various individual adjuvants. Objectives To systematically review adjuvant-related randomized controlled trials and meta-analyses and provide clinical recommendations for the use of adjuvants in peripheral nerve blocks. Methods Randomized controlled trials and meta-analyses that were published between 1990 and 2014 were included in the initial bibliographic search, which was conducted using Medline/PubMed, Cochrane Central Register of Controlled Trials, and EMBASE. Only studies that were published in English and listed block analgesic duration as an outcome were included. Trials that had already been published in the identified meta-analyses and included adjuvants not in widespread use and published without an Investigational New Drug application or equivalent status were excluded. Results Sixty one novel clinical trials and meta-analyses were identified and included in this review. The clinical trials reported analgesic duration data for the following adjuvants: buprenorphine (6), morphine (6), fentanyl (10), epinephrine (3), clonidine (7), dexmedetomidine (7), dexamethasone (7), tramadol (8), and magnesium (4). Studies of perineural buprenorphine, clonidine, dexamethasone, dexmedetomidine, and magnesium most consistently demonstrated prolongation of peripheral nerve blocks. Conclusions Buprenorphine, clonidine, dexamethasone, magnesium, and dexmedetomidine are promising agents for use in prolongation of local anesthetic peripheral nerve blocks, and further studies of safety and efficacy are merited. However, caution is recommended with use of any perineural adjuvant, as none have Food and Drug Administration approval, and concerns for side effects and potential toxicity persist. PMID:26355598

A meta-analysis of Th2 pathway genetic variants and risk for allergic rhinitis.

PubMed

Bunyavanich, Supinda; Shargorodsky, Josef; Celedón, Juan C

2011-06-01

There is a significant genetic contribution to allergic rhinitis (AR). Genetic association studies for AR have been performed, but varying results make it challenging to decipher the overall potential effect of specific variants. The Th2 pathway plays an important role in the immunological development of AR. We performed meta-analyses of genetic association studies of variants in Th2 pathway genes and AR. PubMed and Phenopedia were searched by double extraction for original studies on Th2 pathway-related genetic polymorphisms and their associations with AR. A meta-analysis was conducted on each genetic polymorphism with data meeting our predetermined selection criteria. Analyses were performed using both fixed and random effects models, with stratification by age group, ethnicity, and AR definition where appropriate. Heterogeneity and publication bias were assessed. Six independent studies analyzing three candidate polymorphisms and involving a total of 1596 cases and 2892 controls met our inclusion criteria. Overall, the A allele of IL13 single nucleotide polymorphism (SNP) rs20541 was associated with increased odds of AR (estimated OR=1.2; 95% CI 1.1-1.3, p-value 0.004 in fixed effects model, 95% CI 1.0-1.5, p-value 0.056 in random effects model). The A allele of rs20541 was associated with increased odds of AR in mixed age groups using both fixed effects and random effects modeling. IL13 SNP rs1800925 and IL4R SNP 1801275 did not demonstrate overall associations with AR. We conclude that there is evidence for an overall association between IL13 SNP rs20541 and increased risk of AR, especially in mixed-age populations. © 2011 John Wiley & Sons A/S.

Effectiveness of Valerian on insomnia: a meta-analysis of randomized placebo-controlled trials.

PubMed

Fernández-San-Martín, Maria Isabel; Masa-Font, Roser; Palacios-Soler, Laura; Sancho-Gómez, Pilar; Calbó-Caldentey, Cristina; Flores-Mateo, Gemma

2010-06-01

Insomnia is an often seen primary health care problem. Valerian might be an alternative treatment with fewer secondary effects. The aim of this study is to evaluate its effectiveness on insomnia through a meta-analysis of published literature. Search for randomized clinical trials (RCTs) of Valerian preparations compared with a placebo on Medline, the Cochrane Library, Embase and Biosis. sleep-quality improvement (SQ, yes/no), sleep-quality improvement quantified through visual analogical scales (SQS) and the latency time (LT) in minutes until getting to sleep. Three meta-analyses were carried out using inverse-variance weighted random effects models. Heterogeneity was determined with the Q-statistic and was explored through a sub-groups analysis. Publication bias was evaluated using the funnel plot. Eighteen RCTs were selected; eight had a score of 5 on Jadad's scale. The mean differences in LT between the Valerian and placebo treatment groups was 0.70 min (95% CI, -3.44 to 4.83); the standardized mean differences between the groups measured with SQS was -0.02 (95% CI, -0.35 to 0.31); treatment with Valerian showed a relative risk of SQ of 1.37 (95% CI, 1.05-1.78) compared with the placebo group. There was heterogeneity in the three meta-analyses, but it diminished in the sub groups analysis. No publication bias was detected. The qualitative dichotomous results suggest that valerian would be effective for a subjective improvement of insomnia, although its effectiveness has not been demonstrated with quantitative or objective measurements. We recommend future investigations oriented toward improving insomnia with other more promising treatments. Copyright 2010 Elsevier B.V. All rights reserved.

Enhancing Security of Double Random Phase Encoding Based on Random S-Box

NASA Astrophysics Data System (ADS)

Girija, R.; Singh, Hukum

2018-06-01

In this paper, we propose a novel asymmetric cryptosystem for double random phase encoding (DRPE) using random S-Box. While utilising S-Box separately is not reliable and DRPE does not support non-linearity, so, our system unites the effectiveness of S-Box with an asymmetric system of DRPE (through Fourier transform). The uniqueness of proposed cryptosystem lies on employing high sensitivity dynamic S-Box for our DRPE system. The randomness and scalability achieved due to applied technique is an additional feature of the proposed solution. The firmness of random S-Box is investigated in terms of performance parameters such as non-linearity, strict avalanche criterion, bit independence criterion, linear and differential approximation probabilities etc. S-Boxes convey nonlinearity to cryptosystems which is a significant parameter and very essential for DRPE. The strength of proposed cryptosystem has been analysed using various parameters such as MSE, PSNR, correlation coefficient analysis, noise analysis, SVD analysis, etc. Experimental results are conferred in detail to exhibit proposed cryptosystem is highly secure.

Electroconvulsive Therapy Added to Non-Clozapine Antipsychotic Medication for Treatment Resistant Schizophrenia: Meta-Analysis of Randomized Controlled Trials.

PubMed

Zheng, Wei; Cao, Xiao-Lan; Ungvari, Gabor S; Xiang, Ying-Qiang; Guo, Tong; Liu, Zheng-Rong; Wang, Yuan-Yuan; Forester, Brent P; Seiner, Stephen J; Xiang, Yu-Tao

2016-01-01

This meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of the combination of electroconvulsive therapy (ECT) and antipsychotic medication (except for clozapine) versus the same antipsychotic monotherapy for treatment-resistant schizophrenia (TRS). Two independent investigators extracted data for a random effects meta-analysis and pre-specified subgroup and meta-regression analyses. Weighted and standard mean difference (WMD/SMD), risk ratio (RR) ±95% confidence intervals (CIs), number needed to treat (NNT), and number needed to harm (NNH) were calculated. Eleven studies (n = 818, duration = 10.2±5.5 weeks) were identified for meta-analysis. Adjunctive ECT was superior to antipsychotic monotherapy regarding (1) symptomatic improvement at last-observation endpoint with an SMD of -0.67 (p<0.00001; I2 = 62%), separating the two groups as early as weeks 1–2 with an SMD of -0.58 (p<0.00001; I2 = 0%); (2) study-defined response (RR = 1.48, p<0.0001) with an NNT of 6 (CI = 4–9) and remission rate (RR = 2.18, p = 0.0002) with an NNT of 8 (CI = 6–16); (3) PANSS positive and general symptom sub-scores at endpoint with a WMD between -3.48 to -1.32 (P = 0.01 to 0.009). Subgroup analyses were conducted comparing double blind/rater-masked vs. open RCTs, those with and without randomization details, and high quality (Jadad≥adadup analyses were Jadad<3) studies. The ECT-antipsychotic combination caused more headache (p = 0.02) with an NNH of 6 (CI = 4–11) and memory impairment (p = 0.001) with an NNH of 3 (CI = 2–5). The use of ECT to augment antipsychotic treatment (clozapine excepted) can be an effective treatment option for TRS, with increased frequency of self-reported memory impairment and headache. CRD42014006689 (PROSPERO).

Knowledge translation interventions for critically ill patients: a systematic review*.

PubMed

Sinuff, Tasnim; Muscedere, John; Adhikari, Neill K J; Stelfox, Henry T; Dodek, Peter; Heyland, Daren K; Rubenfeld, Gordon D; Cook, Deborah J; Pinto, Ruxandra; Manoharan, Venika; Currie, Jan; Cahill, Naomi; Friedrich, Jan O; Amaral, Andre; Piquette, Dominique; Scales, Damon C; Dhanani, Sonny; Garland, Allan

2013-11-01

We systematically reviewed ICU-based knowledge translation studies to assess the impact of knowledge translation interventions on processes and outcomes of care. We searched electronic databases (to July, 2010) without language restrictions and hand-searched reference lists of relevant studies and reviews. Two reviewers independently identified randomized controlled trials and observational studies comparing any ICU-based knowledge translation intervention (e.g., protocols, guidelines, and audit and feedback) to management without a knowledge translation intervention. We focused on clinical topics that were addressed in greater than or equal to five studies. Pairs of reviewers abstracted data on the clinical topic, knowledge translation intervention(s), process of care measures, and patient outcomes. For each individual or combination of knowledge translation intervention(s) addressed in greater than or equal to three studies, we summarized each study using median risk ratio for dichotomous and standardized mean difference for continuous process measures. We used random-effects models. Anticipating a small number of randomized controlled trials, our primary meta-analyses included randomized controlled trials and observational studies. In separate sensitivity analyses, we excluded randomized controlled trials and collapsed protocols, guidelines, and bundles into one category of intervention. We conducted meta-analyses for clinical outcomes (ICU and hospital mortality, ventilator-associated pneumonia, duration of mechanical ventilation, and ICU length of stay) related to interventions that were associated with improvements in processes of care. From 11,742 publications, we included 119 investigations (seven randomized controlled trials, 112 observational studies) on nine clinical topics. Interventions that included protocols with or without education improved continuous process measures (seven observational studies and one randomized controlled trial; standardized mean difference [95% CI]: 0.26 [0.1, 0.42]; p = 0.001 and four observational studies and one randomized controlled trial; 0.83 [0.37, 1.29]; p = 0.0004, respectively). Heterogeneity among studies within topics ranged from low to extreme. The exclusion of randomized controlled trials did not change our results. Single-intervention and lower-quality studies had higher standardized mean differences compared to multiple-intervention and higher-quality studies (p = 0.013 and 0.016, respectively). There were no associated improvements in clinical outcomes. Knowledge translation interventions in the ICU that include protocols with or without education are associated with the greatest improvements in processes of critical care.

Genetically Predicted Body Mass Index and Alzheimer’s Disease Related Phenotypes in Three Large Samples: Mendelian Randomization Analyses

PubMed Central

Mukherjee, Shubhabrata; Walter, Stefan; Kauwe, John S.K.; Saykin, Andrew J.; Bennett, David A.; Larson, Eric B.; Crane, Paul K.; Glymour, M. Maria

2015-01-01

Observational research shows that higher body mass index (BMI) increases Alzheimer’s disease (AD) risk, but it is unclear whether this association is causal. We applied genetic variants that predict BMI in Mendelian Randomization analyses, an approach that is not biased by reverse causation or confounding, to evaluate whether higher BMI increases AD risk. We evaluated individual level data from the AD Genetics Consortium (ADGC: 10,079 AD cases and 9,613 controls), the Health and Retirement Study (HRS: 8,403 participants with algorithm-predicted dementia status) and published associations from the Genetic and Environmental Risk for AD consortium (GERAD1: 3,177 AD cases and 7,277 controls). No evidence from individual SNPs or polygenic scores indicated BMI increased AD risk. Mendelian Randomization effect estimates per BMI point (95% confidence intervals) were: ADGC OR=0.95 (0.90, 1.01); HRS OR=1.00 (0.75, 1.32); GERAD1 OR=0.96 (0.87, 1.07). One subscore (cellular processes not otherwise specified) unexpectedly predicted lower AD risk. PMID:26079416

The analgesic effects of exogenous melatonin in humans.

PubMed

Andersen, Lars Peter Holst

2016-10-01

The hormone, melatonin is produced with circadian rhythm by the pineal gland in humans. The melatonin rhythm provides an endogenous synchronizer, modulating e.g. blood pressure, body temperature, cortisol rhythm, sleep-awake-cycle, immune function and anti-oxidative defence. Interestingly, a number of experimental animal studies demonstrate significant dose-dependent anti-nociceptive effects of exogenous melatonin. Similarly, recent experimental- and clinical studies in humans indicate significant analgesic effects. In study I, we systematically reviewed all randomized studies investigating clinical effects of perioperative melatonin. Meta-analyses demonstrated significant analgesic and anxiolytic effects of melatonin in surgical patients, equating reductions of 20 mm and 19 mm, respectively on a VAS, compared with placebo. Profound heterogeneity between the included studies was, however, present. In study II, we aimed to investigate the analgesic, anti-hyperalgesic and anti-inflammatory effects of exogenous melatonin in a validated human inflammatory pain model, the human burn model. The study was performed as a randomized, double blind placebo-controlled crossover study. Primary outcomes were pain during the burn injury and areas of secondary hyperalgesia. No significant effects of exogenous melatonin were observed with respect to primary or secondary outcomes, compared to placebo. Study III and IV estimated the pharmacokinetic variables of exogenous melatonin. Oral melatonin demonstrated a t max value of 41 minutes. Bioavailability of oral melatonin was only 3%. Elimination t 1/2 were approximately 45 minutes following both oral and intravenous administration, respectively. High-dose intravenous melatonin was not associated with increased sedation, in terms of simple reaction times, compared to placebo. Similarly, no other adverse effects were reported. In Study V, we aimed to re-analyse data obtained from a randomized analgesic drug trial by a selection of standard statistical test. Furthermore, we presented an integrated assessment method of longitudinally measured pain intensity and opioid consumption. Our analyses documented that the employed statistical method impacted the statistical significance of post-operative analgesic outcomes. Furthermore, the novel integrated assessment method combines two interdependent outcomes, lowers the risk of type 2 errors, increases the statistical power, and provides a more accurate description of post-operative analgesic efficacy. Exogenous melatonin may offer an effective and safe analgesic drug. At this moment, however, the results of human studies have been contradictory. High-quality randomized experimental- and clinical studies are still needed to establish a "genuine" analgesic effect of the drug in humans. Other perioperative effects of exogenous melatonin should also be investigated, before melatonin can be introduced for clinical routine use in surgical patients. Despite promising experimental and clinical findings, several unanswered questions also relate to optimal dosage, timing of administration and administration route of exogenous melatonin.

Supported employment: cost-effectiveness across six European sites

PubMed Central

Knapp, Martin; Patel, Anita; Curran, Claire; Latimer, Eric; Catty, Jocelyn; Becker, Thomas; Drake, Robert E; Fioritti, Angelo; Kilian, Reinhold; Lauber, Christoph; Rössler, Wulf; Tomov, Toma; van Busschbach, Jooske; Comas-Herrera, Adelina; White, Sarah; Wiersma, Durk; Burns, Tom

2013-01-01

A high proportion of people with severe mental health problems are unemployed but would like to work. Individual Placement and Support (IPS) offers a promising approach to establishing people in paid employment. In a randomized controlled trial across six European countries, we investigated the economic case for IPS for people with severe mental health problems compared to standard vocational rehabilitation. Individuals (n=312) were randomized to receive either IPS or standard vocational services and followed for 18 months. Service use and outcome data were collected. Cost-effectiveness analysis was conducted with two primary outcomes: additional days worked in competitive settings and additional percentage of individuals who worked at least 1 day. Analyses distinguished country effects. A partial cost-benefit analysis was also conducted. IPS produced better outcomes than alternative vocational services at lower cost overall to the health and social care systems. This pattern also held in disaggregated analyses for five of the six European sites. The inclusion of imputed values for missing cost data supported these findings. IPS would be viewed as more cost-effective than standard vocational services. Further analysis demonstrated cost-benefit arguments for IPS. Compared to standard vocational rehabilitation services, IPS is, therefore, probably cost-saving and almost certainly more cost-effective as a way to help people with severe mental health problems into competitive employment. PMID:23471803

Garlic intake lowers fasting blood glucose: meta-analysis of randomized controlled trials.

PubMed

Hou, Li-qiong; Liu, Yun-hui; Zhang, Yi-yi

2015-01-01

Garlic is a common spicy flavouring agent also used for certain therapeutic purposes. Garlic's effects on blood glucose have been the subject of many clinical and animal studies, however, studies reporting hypoglycemic effects of garlic in humans are conflicting. A comprehensive literature search was conducted to identify relevant trials of garlic or garlic extracts on markers of glycemic control [fasting blood glucose (FBG), postprandial glucose (PPG), glycosylated haemoglobin (HbA1c)]. A meta-analysis of the effect of garlic intake on human was done to assess garlic's effectiveness in lowering glucose levels. Two reviewers extracted data from each of the identified studies. Seven eligible randomized controlled trials with 513 subjects were identified. Pooled analyses showed that garlic intake results in a statistically significant lowering in FBG [SMD=-1.67; 95% CI (-2.80, -0.55), p=0.004]. Our pooled analyses did not include PPG control and HbA1c outcomes. Because only 1 study included in the meta-analysis reported PPG variables and only 2 studies reported HbA1c variables. In conclusion, the current meta-analysis showed that the administration of garlic resulted in a significant reduction in FBG concentrations. More trials are needed to investigate the effectiveness of garlic on HbA1c and PPG.

Health-Related Quality-of-Life Findings for the Prostate Cancer Prevention Trial

PubMed Central

2012-01-01

Background The Prostate Cancer Prevention Trial (PCPT)—a randomized placebo-controlled study of the efficacy of finasteride in preventing prostate cancer—offered the opportunity to prospectively study effects of finasteride and other covariates on the health-related quality of life of participants in a multiyear trial. Methods We assessed three health-related quality-of-life domains (measured with the Health Survey Short Form–36: Physical Functioning, Mental Health, and Vitality scales) via questionnaires completed by PCPT participants at enrollment (3 months before randomization), at 6 months after randomization, and annually for 7 years. Covariate data obtained at enrollment from patient-completed questionnaires were included in our model. Mixed-effects model analyses and a cross-sectional presentation at three time points began at 6 months after randomization. All statistical tests were two-sided. Results For the physical function outcome (n = 16 077), neither the finasteride main effect nor the finasteride interaction with time were statistically significant. The effects of finasteride on physical function were minor and accounted for less than a 1-point difference over time in Physical Functioning scores (mixed-effect estimate = 0.07, 95% confidence interval [CI] = −0.28 to 0.42, P = .71). Comorbidities such as congestive heart failure (estimate = −5.64, 95% CI = −7.96 to −3.32, P < .001), leg pain (estimate = −2.57, 95% CI = −3.04 to −2.10, P < .001), and diabetes (estimate = −1.31, 95% CI = −2.04 to −0.57, P < .001) had statistically significant negative effects on physical function, as did current smoking (estimate = −2.34, 95% CI = −2.97 to −1.71, P < .001) and time on study (estimate = −1.20, 95% CI = −1.36 to −1.03, P < .001). Finasteride did not have a statistically significant effect on the other two dependent variables, mental health and vitality, either in the mixed-effects analyses or in the cross-sectional analysis at any of the three time points. Conclusion Finasteride did not negatively affect SF–36 Physical Functioning, Mental Health, or Vitality scores. PMID:22972968

Causal mediation analysis with multiple causally non-ordered mediators.

PubMed

Taguri, Masataka; Featherstone, John; Cheng, Jing

2018-01-01

In many health studies, researchers are interested in estimating the treatment effects on the outcome around and through an intermediate variable. Such causal mediation analyses aim to understand the mechanisms that explain the treatment effect. Although multiple mediators are often involved in real studies, most of the literature considered mediation analyses with one mediator at a time. In this article, we consider mediation analyses when there are causally non-ordered multiple mediators. Even if the mediators do not affect each other, the sum of two indirect effects through the two mediators considered separately may diverge from the joint natural indirect effect when there are additive interactions between the effects of the two mediators on the outcome. Therefore, we derive an equation for the joint natural indirect effect based on the individual mediation effects and their interactive effect, which helps us understand how the mediation effect works through the two mediators and relative contributions of the mediators and their interaction. We also discuss an extension for three mediators. The proposed method is illustrated using data from a randomized trial on the prevention of dental caries.

Effects of a Web-based tailored intervention to reduce alcohol consumption in adults: randomized controlled trial.

PubMed

Schulz, Daniela N; Candel, Math Jjm; Kremers, Stef Pj; Reinwand, Dominique A; Jander, Astrid; de Vries, Hein

2013-09-17

Web-based tailored interventions provide users with information that is adapted to their individual characteristics and needs. Randomized controlled trials assessing the effects of tailored alcohol self-help programs among adults are scarce. Furthermore, it is a challenge to develop programs that can hold respondents' attention in online interventions. To assess whether a 3-session, Web-based tailored intervention is effective in reducing alcohol intake in high-risk adult drinkers and to compare 2 computer-tailoring feedback strategies (alternating vs summative) on behavioral change, dropout, and appreciation of the program. A single-blind randomized controlled trial was conducted with an experimental group and a control group (N=448) in Germany in 2010-2011. Follow-up took place after 6 months. Drinking behavior, health status, motivational determinants, and demographics were assessed among participants recruited via an online access panel. The experimental group was divided into 2 subgroups. In the alternating condition (n=132), the tailored feedback was split into a series of messages discussing individual topics offered while the respondent was filling out the program. Participants in the summative condition (n=181) received all advice at once after having answered all questions. The actual texts were identical for both conditions. The control group (n=135) only filled in 3 questionnaires. To identify intervention effects, logistic and linear regression analyses were conducted among complete cases (n=197) and after using multiple imputation. Among the complete cases (response rate: 197/448, 44.0%) who did not comply with the German national guideline for low-risk drinking at baseline, 21.1% of respondents in the experimental group complied after 6 months compared with 5.8% in the control group (effect size=0.42; OR 2.65, 95% CI 1.14-6.16, P=.02). The experimental group decreased by 3.9 drinks per week compared to 0.4 drinks per week in the control group, but this did not reach statistical significance (effect size=0.26; beta=-0.12, 95% CI -7.96 to 0.03, P=.05). Intention-to-treat analyses also indicated no statistically significant effect. Separate analyses of the 2 experimental subgroups showed no differences in intervention effects. The dropout rate during the first visit to the intervention website was significantly lower in the alternating condition than in the summative condition (OR 0.23, 95% CI 0.08-0.60, P=.003). Program appreciation was comparable for the 2 experimental groups. Complete case analyses revealed that Web-based tailored feedback can be an effective way to reduce alcohol intake among adults. However, this effect was not confirmed when applying multiple imputations. There was no indication that one of the tailoring strategies was more effective in lowering alcohol intake. Nevertheless, the lower attrition rates we found during the first visit suggest that the version of the intervention with alternating questions and advice may be preferred. International Standard Randomized Controlled Trial Number (ISRCTN): 91623132; http://www.controlled-trials.com/ISRCTN91623132 (Archived by WebCite at http://www.webcitation.org/6J4QdhXeG).

Effects of a Web-Based Tailored Intervention to Reduce Alcohol Consumption in Adults: Randomized Controlled Trial

PubMed Central

Candel, Math JJM; Kremers, Stef PJ; Reinwand, Dominique A; Jander, Astrid; de Vries, Hein

2013-01-01

Background Web-based tailored interventions provide users with information that is adapted to their individual characteristics and needs. Randomized controlled trials assessing the effects of tailored alcohol self-help programs among adults are scarce. Furthermore, it is a challenge to develop programs that can hold respondents’ attention in online interventions. Objective To assess whether a 3-session, Web-based tailored intervention is effective in reducing alcohol intake in high-risk adult drinkers and to compare 2 computer-tailoring feedback strategies (alternating vs summative) on behavioral change, dropout, and appreciation of the program. Methods A single-blind randomized controlled trial was conducted with an experimental group and a control group (N=448) in Germany in 2010-2011. Follow-up took place after 6 months. Drinking behavior, health status, motivational determinants, and demographics were assessed among participants recruited via an online access panel. The experimental group was divided into 2 subgroups. In the alternating condition (n=132), the tailored feedback was split into a series of messages discussing individual topics offered while the respondent was filling out the program. Participants in the summative condition (n=181) received all advice at once after having answered all questions. The actual texts were identical for both conditions. The control group (n=135) only filled in 3 questionnaires. To identify intervention effects, logistic and linear regression analyses were conducted among complete cases (n=197) and after using multiple imputation. Results Among the complete cases (response rate: 197/448, 44.0%) who did not comply with the German national guideline for low-risk drinking at baseline, 21.1% of respondents in the experimental group complied after 6 months compared with 5.8% in the control group (effect size=0.42; OR 2.65, 95% CI 1.14-6.16, P=.02). The experimental group decreased by 3.9 drinks per week compared to 0.4 drinks per week in the control group, but this did not reach statistical significance (effect size=0.26; beta=−0.12, 95% CI −7.96 to 0.03, P=.05). Intention-to-treat analyses also indicated no statistically significant effect. Separate analyses of the 2 experimental subgroups showed no differences in intervention effects. The dropout rate during the first visit to the intervention website was significantly lower in the alternating condition than in the summative condition (OR 0.23, 95% CI 0.08-0.60, P=.003). Program appreciation was comparable for the 2 experimental groups. Conclusions Complete case analyses revealed that Web-based tailored feedback can be an effective way to reduce alcohol intake among adults. However, this effect was not confirmed when applying multiple imputations. There was no indication that one of the tailoring strategies was more effective in lowering alcohol intake. Nevertheless, the lower attrition rates we found during the first visit suggest that the version of the intervention with alternating questions and advice may be preferred. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 91623132; http://www.controlled-trials.com/ISRCTN91623132 (Archived by WebCite at http://www.webcitation.org/6J4QdhXeG). PMID:24045005

Timing of surgery for sciatica: subgroup analysis alongside a randomized trial

PubMed Central

Arts, Mark P.; Brand, Ronald; Koes, Bart W.

2009-01-01

Surgery speeds up recovery for sciatica. Prolonged conservative care with surgery for those patients with persistent sciatica however, yields similar results at 1 year. To investigate whether baseline variables modify the difference in recovery rates between these treatment strategies, baseline data of 283 patients enrolled in a randomized trial, comparing early surgery with prolonged conservative care, were used to analyse effect modification of the allotted treatment strategy. For predictors shown to modify the effect of the treatment strategy, repeated measurement analyses with the Roland Disability Questionnaire and visual analogue scale pain as continuous outcomes were performed for every level of that predictor. Presumed predictive variables did not have any interaction with treatment, while “sciatica provoked by sitting” showed to be a significant effect modifier (P = 0.07). In a Cox model we estimated a hazard ratio (HR, surgery versus conservative) of 2.2 (95% CI 1.7–3.0) in favour of surgery when sciatica was provoked by sitting, while the HR was 1.3 (95% CI 0.8–2.2) when this sign was absent. The interaction effect is marginally significant (interactions are usually tested at the 10% level) but the patterns generated by the repeated measurement analyses of all primary outcomes are completely consistent with the inferred pattern from the survival analysis. Classical signs did not show any contribution as decision support tools in deciding when to operate for sciatica, whereas treatment effects of early surgery are emphasized when sciatica is provoked by sitting and negligible when this symptom is absent. PMID:19132412

Psychological mediators related to clinical outcome in cognitive behavioural therapy for coronary heart disease: A sub-analysis from the SUPRIM trial.

PubMed

Norlund, Fredrika; Olsson, Erik Mg; Pingel, Ronnie; Held, Claes; Svärdsudd, Kurt; Gulliksson, Mats; Burell, Gunilla

2017-06-01

Background The Secondary Prevention in Uppsala Primary Healthcare Project (SUPRIM) was a randomized controlled trial of a group-based cognitive behavioural therapy stress management programme for patients with coronary heart disease. The project was successful in reducing the risk of fatal or non-fatal first recurrent cardiovascular events. The aim of this study was to analyse the effect of cognitive behavioural therapy on self-rated stress, somatic anxiety, vital exhaustion and depression and to study the associations of these factors with the reduction in cardiovascular events. Methods A total of 362 patients were randomly assigned to intervention or usual care groups. The psychological outcomes were assessed five times during 24 months and analysed using linear mixed models. The mediating roles of the outcomes were analysed using joint modelling of the longitudinal and time to event data. Results The intervention had a positive effect on somatic anxiety ( p < 0.05), reflecting a beneficial development over time compared with the controls. Stress, vital exhaustion and depression did not differ between the groups over time. Mediator analysis suggested that somatic anxiety may have mediated the effect of treatment on cardiovascular events. Conclusions The intervention had a small positive effect on somatic anxiety, but did not affect stress, vital exhaustion or depression in patients with coronary heart disease. Somatic anxiety was associated with an increased risk of cardiovascular events and might act as a partial mediator in the treatment effect on cardiovascular events. However, the mechanisms between the intervention and the protective cardiovascular outcome remain to be identified.

The Influence of Study-Level Inference Models and Study Set Size on Coordinate-Based fMRI Meta-Analyses

PubMed Central

Bossier, Han; Seurinck, Ruth; Kühn, Simone; Banaschewski, Tobias; Barker, Gareth J.; Bokde, Arun L. W.; Martinot, Jean-Luc; Lemaitre, Herve; Paus, Tomáš; Millenet, Sabina; Moerkerke, Beatrijs

2018-01-01

Given the increasing amount of neuroimaging studies, there is a growing need to summarize published results. Coordinate-based meta-analyses use the locations of statistically significant local maxima with possibly the associated effect sizes to aggregate studies. In this paper, we investigate the influence of key characteristics of a coordinate-based meta-analysis on (1) the balance between false and true positives and (2) the activation reliability of the outcome from a coordinate-based meta-analysis. More particularly, we consider the influence of the chosen group level model at the study level [fixed effects, ordinary least squares (OLS), or mixed effects models], the type of coordinate-based meta-analysis [Activation Likelihood Estimation (ALE) that only uses peak locations, fixed effects, and random effects meta-analysis that take into account both peak location and height] and the amount of studies included in the analysis (from 10 to 35). To do this, we apply a resampling scheme on a large dataset (N = 1,400) to create a test condition and compare this with an independent evaluation condition. The test condition corresponds to subsampling participants into studies and combine these using meta-analyses. The evaluation condition corresponds to a high-powered group analysis. We observe the best performance when using mixed effects models in individual studies combined with a random effects meta-analysis. Moreover the performance increases with the number of studies included in the meta-analysis. When peak height is not taken into consideration, we show that the popular ALE procedure is a good alternative in terms of the balance between type I and II errors. However, it requires more studies compared to other procedures in terms of activation reliability. Finally, we discuss the differences, interpretations, and limitations of our results. PMID:29403344

Maternal Work Early in the Lives of Children and Its Distal Associations with Achievement and Behavior Problems: A Meta-Analysis

ERIC Educational Resources Information Center

Lucas-Thompson, Rachel G.; Goldberg, Wendy A.; Prause, JoAnn

2010-01-01

This meta-analysis of 69 studies (1,483 effect sizes) used random effects models to examine maternal employment during infancy/early childhood in relation to 2 major domains of child functioning: achievement and behavior problems. Analyses of studies that spanned 5 decades indicated that, with a few exceptions, early employment was not…

Preventive Intervention for Preschoolers at High Risk for Antisocial Behavior: Long-Term Effects on Child Physical Aggression and Parenting Practices

ERIC Educational Resources Information Center

Brotman, Laurie Miller; Gouley, Kathleen Kiely; Huang, Keng-Yen; Rosenfelt, Amanda; O'Neal, Colleen; Klein, Rachel G.; Shrout, Patrick

2008-01-01

This article presents long-term effects of a preventive intervention for young children at high risk for antisocial behavior. Ninety-two children (M age = 4 years) were randomly assigned to an 8-month family intervention or no-intervention control condition and assessed 4 times over a 24-month period. Intent-to-treat analyses revealed significant…

Testing feedback message framing and comparators to address prescribing of high-risk medications in nursing homes: protocol for a pragmatic, factorial, cluster-randomized trial.

PubMed

Ivers, Noah M; Desveaux, Laura; Presseau, Justin; Reis, Catherine; Witteman, Holly O; Taljaard, Monica K; McCleary, Nicola; Thavorn, Kednapa; Grimshaw, Jeremy M

2017-07-14

Audit and feedback (AF) interventions that leverage routine administrative data offer a scalable and relatively low-cost method to improve processes of care. AF interventions are usually designed to highlight discrepancies between desired and actual performance and to encourage recipients to act to address such discrepancies. Comparing to a regional average is a common approach, but more recipients would have a discrepancy if compared to a higher-than-average level of performance. In addition, how recipients perceive and respond to discrepancies may depend on how the feedback itself is framed. We aim to evaluate the effectiveness of different comparators and framing in feedback on high-risk prescribing in nursing homes. This is a pragmatic, 2 × 2 factorial, cluster-randomized controlled trial testing variations in the comparator and framing on the effectiveness of quarterly AF in changing high-risk prescribing in nursing homes in Ontario, Canada. We grouped homes that share physicians into clusters and randomized these clusters into the four experimental conditions. Outcomes will be assessed after 6 months; all primary analyses will be by intention-to-treat. The primary outcome (monthly number of high-risk medications received by each patient) will be analysed using a general linear mixed effects regression model. We will present both four-arm and factorial analyses. With 160 clusters and an average of 350 beds per cluster, assuming no interaction and similar effects for each intervention, we anticipate 90% power to detect an absolute mean difference of 0.3 high-risk medications prescribed. A mixed-methods process evaluation will explore potential mechanisms underlying the observed effects, exploring targeted constructs including intention, self-efficacy, outcome expectations, descriptive norms, and goal prioritization. An economic analysis will examine cost-effectiveness analysis from the perspective of the publicly funded health care system. This protocol describes the rationale and methodology of a trial testing manipulations of theory-informed components of an audit and feedback intervention to determine how to improve an existing intervention and provide generalizable insights for implementation science. NCT02979964.

Effects of Cognitive Enhancement Therapy on Employment Outcomes in Early Schizophrenia: Results From a Two-Year Randomized Trial

PubMed Central

Eack, Shaun M.; Hogarty, Gerard E.; Greenwald, Deborah P.; Hogarty, Susan S.; Keshavan, Matcheri S.

2013-01-01

Objective To examine the effects of psychosocial cognitive rehabilitation on employment outcomes in a randomized controlled trial for individuals with early course schizophrenia. Method Early course schizophrenia outpatients (N = 58) were randomly assigned to Cognitive Enhancement Therapy (CET) or an Enriched Supportive Therapy (EST) control and treated for two years. Comprehensive data on cognition and employment were collected annually. Results Individuals treated with CET were significantly more likely to be competitively employed, had greater earnings from employment, and were more satisfied with their employment status by the end of treatment compared to EST recipients. Mediator analyses revealed that improvements in both social and non-social cognition mediated the CET effects on employment. Conclusion CET can help facilitate employment in early schizophrenia, by addressing the cognitive impairments that limit functioning in the disorder. Inclusion of cognitive rehabilitation in social work practice can support more optimal functional recovery from schizophrenia. PMID:23885163

Birth order, neuroticism, and psychoticism among Iranian children.

PubMed

Makaremi, A

1992-12-01

To investigate the effects of birth order, parents' education, and parents' occupation on four dimensions of the Junior Eysenck Personality Questionnaire, 262 elementary school students (100 boys and 162 girls) were selected randomly from four elementary schools in Shiraz. Analyses showed the main effects of birth order were significant on Neuroticism and Lie scales. Further, the effects of mothers' occupation on the Lie scale and fathers' education on the Neuroticism scale were significant.

Improving preschoolers' mathematics achievement with tablets: a randomized controlled trial

NASA Astrophysics Data System (ADS)

Schacter, John; Jo, Booil

2017-09-01

With a randomized field experiment of 433 preschoolers, we tested a tablet mathematics program designed to increase young children's mathematics learning. Intervention students played Math Shelf, a comprehensive iPad preschool and year 1 mathematics app, while comparison children received research-based hands-on mathematics instruction delivered by their classroom teachers. After 22 weeks, there was a large and statistically significant effect on mathematics achievement for Math Shelf students (Cohen's d = .94). Moderator analyses demonstrated an even larger effect for low achieving children (Cohen's d = 1.27). These results suggest that early education teachers can improve their students' mathematics outcomes by integrating experimentally proven tablet software into their daily routines.

Pilot study of the Korean Parent Training Program using a partial group randomized experimental study

PubMed Central

Kim, Eunjung; Cain, Kevin; Boutain, Doris; Chun, Jin-Joo; Kim, Sangho; Im, Hyesang

2017-01-01

Problems Korean American (KA) children experience mental health problems due to difficulties in parenting dysfunction complicated by living in two cultures. Methods Korean Parent Training Program (KPTP) was pilot tested with 48 KA mothers of children (ages 3–8) using partial group randomized controlled experimental study design. Self-report survey and observation data were gathered. Findings Analyses using generalized estimating equation indicated the intervention group mothers increased effective parenting and their children decreased behavior problems and reported less acculturation conflict with mothers. Conclusions The KPTP is a promising way to promote effective parenting and increase positive child mental health in KA families. PMID:24645901

Effects of online cognitive treatment for problematic anger: a randomized controlled trial.

PubMed

Howie, Amanda J; Malouff, John M

2014-01-01

Problematic anger, which is common, has been associated with a wide range of negative interpersonal and intrapersonal consequences, including violent behaviour, relationship damage, health problems and low self-esteem. This article reports the results of the first randomized controlled trial of brief online cognitive treatment for anger. The sample included 75 adults who were randomly assigned to cognitive treatment or a waiting list control. The analyses with the 59 participants who completed the post-intervention assessment at four weeks after the beginning of the intervention showed that individuals who received the intervention reported significantly lower anger levels than the control group at post-assessment. The treatment group showed a substantial decrease in anger from pre to post. The results suggest that brief online cognitive treatment can be effective for reducing problematic anger in adults. These findings provide an initial support for the development of internet-based cognitive treatment for problematic anger.

Statistical analysis plan for the Pneumatic CompREssion for PreVENting Venous Thromboembolism (PREVENT) trial: a study protocol for a randomized controlled trial.

PubMed

Arabi, Yaseen; Al-Hameed, Fahad; Burns, Karen E A; Mehta, Sangeeta; Alsolamy, Sami; Almaani, Mohammed; Mandourah, Yasser; Almekhlafi, Ghaleb A; Al Bshabshe, Ali; Finfer, Simon; Alshahrani, Mohammed; Khalid, Imran; Mehta, Yatin; Gaur, Atul; Hawa, Hassan; Buscher, Hergen; Arshad, Zia; Lababidi, Hani; Al Aithan, Abdulsalam; Jose, Jesna; Abdukahil, Sheryl Ann I; Afesh, Lara Y; Dbsawy, Maamoun; Al-Dawood, Abdulaziz

2018-03-15

The Pneumatic CompREssion for Preventing VENous Thromboembolism (PREVENT) trial evaluates the effect of adjunctive intermittent pneumatic compression (IPC) with pharmacologic thromboprophylaxis compared to pharmacologic thromboprophylaxis alone on venous thromboembolism (VTE) in critically ill adults. In this multicenter randomized trial, critically ill patients receiving pharmacologic thromboprophylaxis will be randomized to an IPC or a no IPC (control) group. The primary outcome is "incident" proximal lower-extremity deep vein thrombosis (DVT) within 28 days after randomization. Radiologists interpreting the lower-extremity ultrasonography will be blinded to intervention allocation, whereas the patients and treating team will be unblinded. The trial has 80% power to detect a 3% absolute risk reduction in the rate of proximal DVT from 7% to 4%. Consistent with international guidelines, we have developed a detailed plan to guide the analysis of the PREVENT trial. This plan specifies the statistical methods for the evaluation of primary and secondary outcomes, and defines covariates for adjusted analyses a priori. Application of this statistical analysis plan to the PREVENT trial will facilitate unbiased analyses of clinical data. ClinicalTrials.gov , ID: NCT02040103 . Registered on 3 November 2013; Current controlled trials, ID: ISRCTN44653506 . Registered on 30 October 2013.

Antiviral treatment of Bell's palsy based on baseline severity: a systematic review and meta-analysis.

PubMed

Turgeon, Ricky D; Wilby, Kyle J; Ensom, Mary H H

2015-06-01

We conducted a systematic review with meta-analysis to evaluate the efficacy of antiviral agents on complete recovery of Bell's palsy. We searched CENTRAL, Embase, MEDLINE, International Pharmaceutical Abstracts, and sources of unpublished literature to November 1, 2014. Primary and secondary outcomes were complete and satisfactory recovery, respectively. To evaluate statistical heterogeneity, we performed subgroup analysis of baseline severity of Bell's palsy and between-study sensitivity analyses based on risk of allocation and detection bias. The 10 included randomized controlled trials (2419 patients; 807 with severe Bell's palsy at onset) had variable risk of bias, with 9 trials having a high risk of bias in at least 1 domain. Complete recovery was not statistically significantly greater with antiviral use versus no antiviral use in the random-effects meta-analysis of 6 trials (relative risk, 1.06; 95% confidence interval, 0.97-1.16; I(2) = 65%). Conversely, random-effects meta-analysis of 9 trials showed a statistically significant difference in satisfactory recovery (relative risk, 1.10; 95% confidence interval, 1.02-1.18; I(2) = 63%). Response to antiviral agents did not differ visually or statistically between patients with severe symptoms at baseline and those with milder disease (test for interaction, P = .11). Sensitivity analyses did not show a clear effect of bias on outcomes. Antiviral agents are not efficacious in increasing the proportion of patients with Bell's palsy who achieved complete recovery, regardless of baseline symptom severity. Copyright © 2015 Elsevier Inc. All rights reserved.

Raloxifene for women with Alzheimer disease

PubMed Central

Ala, Tom; Sainani, Kristin L.; Bernstein, Allan L.; Stephenson, B. Sue; Rosen, Allyson C.; Farlow, Martin R.

2015-01-01

Objective: To determine whether raloxifene, a selective estrogen receptor modulator, improves cognitive function compared with placebo in women with Alzheimer disease (AD) and to provide an estimate of cognitive effect. Methods: This pilot study was conducted as a randomized, double-blind, placebo-controlled trial, with a planned treatment of 12 months. Women with late-onset AD of mild to moderate severity were randomly allocated to high-dose (120 mg) oral raloxifene or identical placebo provided once daily. The primary outcome compared between treatment groups at 12 months was change in the Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS-cog). Results: Forty-two women randomized to raloxifene or placebo were included in intent-to-treat analyses (mean age 76 years, range 68–84), and 39 women contributed 12-month outcomes. ADAS-cog change scores at 12 months did not differ significantly between treatment groups (standardized difference 0.03, 95% confidence interval −0.39 to 0.44, 2-tailed p = 0.89). Raloxifene and placebo groups did not differ significantly on secondary analyses of dementia rating, activities of daily living, behavior, or a global cognition composite score. Caregiver burden and caregiver distress were similar in both groups. Conclusions: Results on the primary outcome showed no cognitive benefits in the raloxifene-treated group. Classification of evidence: This study provides Class I evidence that for women with AD, raloxifene does not have a significant cognitive effect. The study lacked the precision to exclude a small effect. PMID:26537053

Systematic review: proton pump inhibitors (PPIs) for the healing of reflux oesophagitis - a comparison of esomeprazole with other PPIs.

PubMed

Edwards, S J; Lind, T; Lundell, L

2006-09-01

No randomized controlled trial has compared all the licensed standard dose proton pump inhibitors in the healing of reflux oesophagitis. To compare the effectiveness of esomeprazole with licensed standard dose proton pump inhibitors for healing of reflux oesophagitis (i.e. lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg and rabeprazole 20 mg). Systematic review of CENTRAL, BIOSIS, EMBASE and MEDLINE for randomized controlled trials in patients with reflux oesophagitis. Searching was completed in February 2005. Data on endoscopic healing rates at 4 and 8 weeks were extracted and re-analysed if not analysed by intention-to-treat. Meta-analysis was conducted using a fixed effects model. Of 133 papers identified in the literature search, six were of sufficient quality to be included in the analysis. No studies were identified comparing rabeprazole with esomeprazole. A meta-analysis of healing rates of esomeprazole 40 mg compared with standard dose proton pump inhibitors gave the following results: at 4 weeks [relative risk (RR) 0.92; 95% CI: 0.90, 0.94; P < 0.00001], and 8 weeks (RR 0.95; 95% CI: 0.94, 0.97; P < 0.00001). Publication bias did not have a significant impact on the results. The results were robust to changes in the inclusion/exclusion criteria and using a random effects model. Esomeprazole consistently demonstrates higher healing rates when compared with standard dose proton pump inhibitors.

Effects of physical activity on schoolchildren's academic performance: The Active Smarter Kids (ASK) cluster-randomized controlled trial.

PubMed

Resaland, Geir K; Aadland, Eivind; Moe, Vegard Fusche; Aadland, Katrine N; Skrede, Turid; Stavnsbo, Mette; Suominen, Laura; Steene-Johannessen, Jostein; Glosvik, Øyvind; Andersen, John R; Kvalheim, Olav M; Engelsrud, Gunn; Andersen, Lars B; Holme, Ingar M; Ommundsen, Yngvar; Kriemler, Susi; van Mechelen, Willem; McKay, Heather A; Ekelund, Ulf; Anderssen, Sigmund A

2016-10-01

To investigate the effect of a seven-month, school-based cluster-randomized controlled trial on academic performance in 10-year-old children. In total, 1129 fifth-grade children from 57 elementary schools in Sogn og Fjordane County, Norway, were cluster-randomized by school either to the intervention group or to the control group. The children in the 28 intervention schools participated in a physical activity intervention between November 2014 and June 2015 consisting of three components: 1) 90min/week of physically active educational lessons mainly carried out in the school playground; 2) 5min/day of physical activity breaks during classroom lessons; 3) 10min/day physical activity homework. Academic performance in numeracy, reading and English was measured using standardized Norwegian national tests. Physical activity was measured objectively by accelerometry. We found no effect of the intervention on academic performance in primary analyses (standardized difference 0.01-0.06, p>0.358). Subgroup analyses, however, revealed a favorable intervention effect for those who performed the poorest at baseline (lowest tertile) for numeracy (p=0.005 for the subgroup∗group interaction), compared to controls (standardized difference 0.62, 95% CI 0.19-1.07). This large, rigorously conducted cluster RCT in 10-year-old children supports the notion that there is still inadequate evidence to conclude that increased physical activity in school enhances academic achievement in all children. Still, combining physical activity and learning seems a viable model to stimulate learning in those academically weakest schoolchildren. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Effect of a smoking cessation intervention for women in subsidized neighborhoods: A randomized controlled trial.

PubMed

Andrews, Jeannette O; Mueller, Martina; Dooley, Mary; Newman, Susan D; Magwood, Gayenell S; Tingen, Martha S

2016-09-01

To evaluate the effectiveness of a community based participatory research (CBPR) developed, multi-level smoking cessation intervention among women in subsidized housing neighborhoods in the Southeastern US. A total of n=409 women in 14 subsidized housing neighborhoods in Georgia and South Carolina participated in this group randomized controlled trial conducted from 2009 to 2013. Intervention neighborhoods received a 24-week intervention with 1:1 community health worker contact, behavioral peer group sessions, and nicotine replacement. Control neighborhoods received written cessation materials at weeks 1, 6, 12, 18. Random coefficient models were used to compare smoking abstinence outcomes at 6 and 12months. Significance was set a p<0.05. The majority of participants (91.2%) were retained during the 12-month intervention period. Smoking abstinence rates at 12months for intervention vs. control were 9% vs. 4.3%, p=0.05. Additional analyses accounting for passive smoke exposure in these multi-unit housing settings demonstrated 12month abstinence rates of 12% vs. 5.3%, p=0.016. However, in the multivariate regression analyses, there was no significant effect of the intervention on the odds of being a non-smoker (OR=0.44, 95% CI: 0.18-1.07). Intervention participants who kept coach visits, attended group sessions, and used patches were more likely to remain abstinent. This CBPR developed intervention showed potential to engage smokers and reduce smoking among women in these high-poverty neighborhoods. Effectiveness in promoting cessation in communities burdened with fiscal, environmental and social inequities remains a public health priority. Copyright © 2016 Elsevier Inc. All rights reserved.

An analysis of random projection for changeable and privacy-preserving biometric verification.

PubMed

Wang, Yongjin; Plataniotis, Konstantinos N

2010-10-01

Changeability and privacy protection are important factors for widespread deployment of biometrics-based verification systems. This paper presents a systematic analysis of a random-projection (RP)-based method for addressing these problems. The employed method transforms biometric data using a random matrix with each entry an independent and identically distributed Gaussian random variable. The similarity- and privacy-preserving properties, as well as the changeability of the biometric information in the transformed domain, are analyzed in detail. Specifically, RP on both high-dimensional image vectors and dimensionality-reduced feature vectors is discussed and compared. A vector translation method is proposed to improve the changeability of the generated templates. The feasibility of the introduced solution is well supported by detailed theoretical analyses. Extensive experimentation on a face-based biometric verification problem shows the effectiveness of the proposed method.

Subgroup analysis of telehealthcare for patients with chronic obstructive pulmonary disease: the cluster-randomized Danish Telecare North Trial

PubMed Central

Witt Udsen, Flemming; Lilholt, Pernille H; Hejlesen, Ole K; Ehlers, Lars H

2017-01-01

Purpose Results from the Danish cluster-randomized trial of telehealthcare to 1,225 patients with chronic obstructive pulmonary disease (COPD), the Danish Telecare North Trial, concluded that the telehealthcare solution was unlikely to be cost-effective, by applying international willingness-to-pay threshold values. The purpose of this article was to assess potential sources of variation across subgroups, which could explain overall cost-effectiveness results or be utilized in future economic studies in telehealthcare research. Methods First, the cost-structures and cost-effectiveness across COPD severities were analyzed. Second, five additional subgroup analyses were conducted, focusing on differences in cost-effectiveness across a set of comorbidities, age-groups, genders, resource patterns (resource use in the social care sector prior to randomization), and delivery sites. All subgroups were investigated post hoc. In analyzing cost-effectiveness, two separate linear mixed-effects models with treatment-by-covariate interactions were applied: one for quality-adjusted life-year (QALY) gain and one for total healthcare and social sector costs. Probabilistic sensitivity analysis was used for each subgroup result in order to quantify the uncertainty around the cost-effectiveness results. Results The study concludes that, across the COPD severities, patients with severe COPD (GOLD 3 classification) are likely to be the most cost-effective group. This is primarily due to lower hospital-admission and primary-care costs. Telehealthcare for patients younger than 60 years is also more likely to be cost-effective than for older COPD patients. Overall, results indicate that existing resource patterns of patients and variations in delivery-site practices might have a strong influence on cost-effectiveness, possibly stronger than the included health or sociodemographic sources of heterogeneity. Conclusion Future research should focus more on sources of heterogeneity found in the implementation context and the way telehealthcare is adopted (eg, by integrating formative evaluation into cost-effectiveness analyses). Trial registration Clinicaltrials.gov, NCT01984840. PMID:28740411

The Evaluation of Bivariate Mixed Models in Meta-analyses of Diagnostic Accuracy Studies with SAS, Stata and R.

PubMed

Vogelgesang, Felicitas; Schlattmann, Peter; Dewey, Marc

2018-05-01

Meta-analyses require a thoroughly planned procedure to obtain unbiased overall estimates. From a statistical point of view not only model selection but also model implementation in the software affects the results. The present simulation study investigates the accuracy of different implementations of general and generalized bivariate mixed models in SAS (using proc mixed, proc glimmix and proc nlmixed), Stata (using gllamm, xtmelogit and midas) and R (using reitsma from package mada and glmer from package lme4). Both models incorporate the relationship between sensitivity and specificity - the two outcomes of interest in meta-analyses of diagnostic accuracy studies - utilizing random effects. Model performance is compared in nine meta-analytic scenarios reflecting the combination of three sizes for meta-analyses (89, 30 and 10 studies) with three pairs of sensitivity/specificity values (97%/87%; 85%/75%; 90%/93%). The evaluation of accuracy in terms of bias, standard error and mean squared error reveals that all implementations of the generalized bivariate model calculate sensitivity and specificity estimates with deviations less than two percentage points. proc mixed which together with reitsma implements the general bivariate mixed model proposed by Reitsma rather shows convergence problems. The random effect parameters are in general underestimated. This study shows that flexibility and simplicity of model specification together with convergence robustness should influence implementation recommendations, as the accuracy in terms of bias was acceptable in all implementations using the generalized approach. Schattauer GmbH.

Exercise improves depressive symptoms in older adults: An umbrella review of systematic reviews and meta-analyses.

PubMed

Catalan-Matamoros, Daniel; Gomez-Conesa, Antonia; Stubbs, Brendon; Vancampfort, Davy

2016-10-30

Late-life depression is a growing public health concern. Exercise may be of added value but the literature remains equivocal. We conducted a systematic overview of meta-analyses and an exploratory pooled analysis of previous meta-analyses to determine the effect of exercise on depression in older adults. Two independent researchers searched Pubmed, CINAHL, Cochrane Plus, PsycArticles, and PsycInfo for meta-analyses on exercise in late-life depression. Methodological quality was assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) Instrument. We pooled effect sizes from previous meta-analyses of randomized controlled trials to determine the effect of exercise on depression in older adults. The systematic review yielded 3 meta-analyses. In total, 16 unique cohorts of 1487 participants were included. The quality of the three included meta-analyses was considered as "moderate" according to AMSTAR scores. No serious adverse events were reported. Compared to controls (n=583), those exercising (n=541) significantly reduced depressive symptoms. Our umbrella review indicates that exercise is safe and efficacious in reducing depressive symptoms in older people. Since exercise has many other known health benefits, it should be considered as a core intervention in the multidisciplinary treatment of older adults experiencing depression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Intra-Aortic Balloon Pump Counterpulsation during Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction and Cardiogenic Shock: Insights from the British Columbia Cardiac Registry

PubMed Central

Iqbal, M. Bilal; Robinson, Simon D.; Ding, Lillian; Fung, Anthony; Aymong, Eve; Chan, Albert W.; Hodge, Steven; Della Siega, Anthony; Nadra, Imad J.

2016-01-01

Background Cardiogenic shock complicating ST-elevation myocardial infarction (STEMI) is associated with significant morbidity and mortality. In the primary percutaneous coronary intervention (PPCI) era, randomized trials have not shown a survival benefit with intra-aortic balloon pump (IABP) therapy. This differs to observational data which show a detrimental effect, potentially reflecting bias and confounding. Without robust and valid risk adjustment, findings from non-randomized studies may remain biased. Methods We compared long-term mortality following IABP therapy in patients with cardiogenic shock undergoing PPCI during 2008–2013 from the British Columbia Cardiac Registry. We addressed measured and unmeasured confounding using propensity score and instrumental variable methods. Results A total of 12,105 patients with STEMI were treated with PPCI during the study period. Of these, 700 patients (5.8%) had cardiogenic shock. Of the patients with cardiogenic shock, 255 patients (36%) received IABP therapy. Multivariable analyses identified IABP therapy to be associated with increased mortality up to 3 years (HR = 1.67, 95% CI:1.20–2.67, p<0.001). This association was lost in propensity-matched analyses (HR = 1.23, 95% CI: 0.84–1.80, p = 0.288). When addressing measured and unmeasured confounders, instrumental variable analyses demonstrated that IABP therapy was not associated with mortality at 3 years (Δ = 16.7%, 95% CI: -12.7%, 46.1%, p = 0.281). Subgroup analyses demonstrated IABP was associated with increased mortality in non-diabetics; patients not undergoing multivessel intervention; patients without renal disease and patients not having received prior thrombolysis. Conclusions In this observational analysis of patients with STEMI and cardiogenic shock, when adjusting for confounding, IABP therapy had a neutral effect with no association with long-term mortality. These findings differ to previously reported observational studies, but are in keeping with randomized trial data. PMID:26870950

Dose-related beneficial and harmful effects of gabapentin in postoperative pain management – post hoc analyses from a systematic review with meta-analyses and trial sequential analyses

PubMed Central

Fabritius, Maria Louise; Wetterslev, Jørn; Mathiesen, Ole; Dahl, Jørgen B

2017-01-01

Background During the last 15 years, gabapentin has become an established component of postoperative pain treatment. Gabapentin has been employed in a wide range of doses, but little is known about the optimal dose, providing the best balance between benefit and harm. This systematic review with meta-analyses aimed to explore the beneficial and harmful effects of various doses of gabapentin administered to surgical patients. Materials and methods Data in this paper were derived from an original review, and the subgroup analyses were predefined in an International Prospective Register of Systematic Reviews published protocol: PROSPERO (ID: CRD42013006538). The methods followed Cochrane guidelines. The Cochrane Library’s CENTRAL, PubMed, EMBASE, Science Citation Index Expanded, Google Scholar, and FDA database were searched for relevant trials. Randomized clinical trials comparing gabapentin versus placebo were included. Four different dose intervals were investigated: 0–350, 351–700, 701–1050, and >1050 mg. Primary co-outcomes were 24-hour morphine consumption and serious adverse events (SAEs), with emphasis put on trials with low risk of bias. Results One hundred and twenty-two randomized clinical trials, with 8466 patients, were included. Sixteen were overall low risk of bias. No consistent increase in morphine-sparing effect was observed with increasing doses of gabapentin from the trials with low risk of bias. Analyzing all trials, the smallest and the highest dose subgroups demonstrated numerically the most prominent reduction in morphine consumption. Twenty-seven trials reported 72 SAEs, of which 83% were reported in the >1050 mg subgroup. No systematic increase in SAEs was observed with increasing doses of gabapentin. Conclusion Data were sparse, and the small number of trials with low risk of bias is a major limitation for firm conclusions. Taking these limitations into account, we were not able to demonstrate a clear relationship between the dosage of gabapentin and opioid-sparing or harmful effects. These subgroup analyses are exploratory and hypothesis-generating for future trialists. PMID:29138592

Effect of Fruit Juice on Glucose Control and Insulin Sensitivity in Adults: A Meta-Analysis of 12 Randomized Controlled Trials

PubMed Central

Mi, Mantian; Wang, Jian

2014-01-01

Background Diabetes mellitus has become a worldwide health problem. Whether fruit juice is beneficial in glycemic control is still inconclusive. This study aimed to synthesize evidence from randomized controlled trials on fruit juice in relationship to glucose control and insulin sensitivity. Methods A strategic literature search of PubMed, EMBASE, and the Cochrane Library (updated to March, 2014) was performed to retrieve the randomized controlled trials that evaluated the effects of fruit juice on glucose control and insulin sensitivity. Study quality was assessed using the Jadad scale. Weighted mean differences were calculated for net changes in the levels of fasting glucose, fasting insulin, hemoglobin A1c (HbA1c), and homeostatic model assessment of insulin resistance (HOMA-IR) using fixed- or random-effects model. Prespecified subgroup and sensitivity analyses were performed to explore the potential heterogeneity. Results Twelve trials comprising a total of 412 subjects were included in the current meta-analysis. The numbers of these studies that reported the data on fasting glucose, fasting insulin, HbA1c and HOMA-IR were 12, 5, 3 and 3, respectively. Fruit juice consumption did not show a significant effect on fasting glucose and insulin concentrations. The net change was 0.79 mg/dL (95% CI: −1.44, 3.02 mg/dL; P = 0.49) for fasting glucose concentrations and −0.74 µIU/ml (95% CI: −2.62, 1.14 µIU/ml; P = 0.44) for fasting insulin concentrations in the fixed-effects model. Subgroup analyses further suggested that the effect of fruit juice on fasting glucose concentrations was not influenced by population region, baseline glucose concentration, duration, type of fruit juice, glycemic index of fruit juice, fruit juice nutrient constitution, total polyphenols dose and Jadad score. Conclusion This meta-analysis showed that fruit juice may have no overall effect on fasting glucose and insulin concentrations. More RCTs are warranted to further clarify the association between fruit juice and glycemic control. PMID:24743260

Random sampling of constrained phylogenies: conducting phylogenetic analyses when the phylogeny is partially known.

PubMed

Housworth, E A; Martins, E P

2001-01-01

Statistical randomization tests in evolutionary biology often require a set of random, computer-generated trees. For example, earlier studies have shown how large numbers of computer-generated trees can be used to conduct phylogenetic comparative analyses even when the phylogeny is uncertain or unknown. These methods were limited, however, in that (in the absence of molecular sequence or other data) they allowed users to assume that no phylogenetic information was available or that all possible trees were known. Intermediate situations where only a taxonomy or other limited phylogenetic information (e.g., polytomies) are available are technically more difficult. The current study describes a procedure for generating random samples of phylogenies while incorporating limited phylogenetic information (e.g., four taxa belong together in a subclade). The procedure can be used to conduct comparative analyses when the phylogeny is only partially resolved or can be used in other randomization tests in which large numbers of possible phylogenies are needed.

Degradation mechanisms of bioresorbable polyesters. Part 2. Effects of initial molecular weight and residual monomer.

PubMed

Gleadall, Andrew; Pan, Jingzhe; Kruft, Marc-Anton; Kellomäki, Minna

2014-05-01

This paper presents an understanding of how initial molecular weight and initial monomer fraction affect the degradation of bioresorbable polymers in terms of the underlying hydrolysis mechanisms. A mathematical model was used to analyse the effects of initial molecular weight for various hydrolysis mechanisms including noncatalytic random scission, autocatalytic random scission, noncatalytic end scission or autocatalytic end scission. Different behaviours were identified to relate initial molecular weight to the molecular weight half-life and to the time until the onset of mass loss. The behaviours were validated by fitting the model to experimental data for molecular weight reduction and mass loss of samples with different initial molecular weights. Several publications that consider initial molecular weight were reviewed. The effect of residual monomer on degradation was also analysed, and shown to accelerate the reduction of molecular weight and mass loss. An inverse square root law relationship was found between molecular weight half-life and initial monomer fraction for autocatalytic hydrolysis. The relationship was tested by fitting the model to experimental data with various residual monomer contents. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Immediate changes in widespread pressure pain sensitivity, neck pain, and cervical range of motion after cervical or thoracic thrust manipulation in patients with bilateral chronic mechanical neck pain: a randomized clinical trial.

PubMed

Martínez-Segura, Raquel; De-la-Llave-Rincón, Ana I; Ortega-Santiago, Ricardo; Cleland, Joshua A; Fernández-de-Las-Peñas, César

2012-09-01

Randomized clinical trial. To compare the effects of cervical versus thoracic thrust manipulation in patients with bilateral chronic mechanical neck pain on pressure pain sensitivity, neck pain, and cervical range of motion (CROM). Evidence suggests that spinal interventions can stimulate descending inhibitory pain pathways. To our knowledge, no study has investigated the neurophysiological effects of thoracic thrust manipulation in individuals with bilateral chronic mechanical neck pain, including widespread changes on pressure sensitivity. Ninety patients (51% female) were randomly assigned to 1 of 3 groups: cervical thrust manipulation on the right, cervical thrust manipulation on the left, or thoracic thrust manipulation. Pressure pain thresholds (PPTs) over the C5-6 zygapophyseal joint, lateral epicondyle, and tibialis anterior muscle, neck pain (11-point numeric pain rating scale), and cervical spine range of motion (CROM) were collected at baseline and 10 minutes after the intervention by an assessor blinded to the treatment allocation of the patients. Mixed-model analyses of covariance were used to examine the effects of the treatment on each outcome variable, with group as the between-subjects variable, time and side as the within-subject variables, and gender as the covariate. The primary analysis was the group-by-time interaction. No significant interactions were found with the mixed-model analyses of covariance for PPT level (C5-6, P>.210; lateral epicondyle, P>.186; tibialis anterior muscle, P>.268), neck pain intensity (P = .923), or CROM (flexion, P = .700; extension, P = .387; lateral flexion, P>.672; rotation, P>.192) as dependent variables. All groups exhibited similar changes in PPT, neck pain, and CROM (all, P<.001). Gender did not influence the main effects or the interaction effects in the analyses of the outcomes (P>.10). The results of the current randomized clinical trial suggest that cervical and thoracic thrust manipulation induce similar changes in PPT, neck pain intensity, and CROM in individuals with bilateral chronic mechanical neck pain. However, changes in PPT and CROM were small and did not surpass their respective minimal detectable change values. Further, because we did not include a control group, we cannot rule out a placebo effect of the thrust interventions on the outcomes. Therapy, level 1b.J Orthop Sports Phys Ther 2012;42(9):806-814, Epub 18 June 2012. doi:10.2519/jospt.2012.4151.

A semiparametric Bayesian proportional hazards model for interval censored data with frailty effects.

PubMed

Henschel, Volkmar; Engel, Jutta; Hölzel, Dieter; Mansmann, Ulrich

2009-02-10

Multivariate analysis of interval censored event data based on classical likelihood methods is notoriously cumbersome. Likelihood inference for models which additionally include random effects are not available at all. Developed algorithms bear problems for practical users like: matrix inversion, slow convergence, no assessment of statistical uncertainty. MCMC procedures combined with imputation are used to implement hierarchical models for interval censored data within a Bayesian framework. Two examples from clinical practice demonstrate the handling of clustered interval censored event times as well as multilayer random effects for inter-institutional quality assessment. The software developed is called survBayes and is freely available at CRAN. The proposed software supports the solution of complex analyses in many fields of clinical epidemiology as well as health services research.

Chinese Herbal Bath Therapy for the Treatment of Knee Osteoarthritis: Meta-Analysis of Randomized Controlled Trials

PubMed Central

Chen, Bo; Zhan, Hongsheng; Chung, Mei; Lin, Xun; Zhang, Min; Pang, Jian; Wang, Chenchen

2015-01-01

Objective. Chinese herbal bath therapy (CHBT) has traditionally been considered to have analgesic and anti-inflammatory effects. We conducted the first meta-analysis evaluating its benefits for patients with knee osteoarthritis (OA). Methods. We searched three English and four Chinese databases through October, 2014. Randomized trials evaluating at least 2 weeks of CHBT for knee OA were selected. The effects of CHBT on clinical symptoms included both pain level (via the visual analog scale) and total effectiveness rate, which assessed pain, physical performance, and wellness. We performed random-effects meta-analyses using mean difference. Results. Fifteen studies totaling 1618 subjects met eligibility criteria. Bath prescription included, on average, 13 Chinese herbs with directions to steam and wash around the knee for 20–40 minutes once or twice daily. Mean treatment duration was 3 weeks. Results from meta-analysis showed superior pain improvement (mean difference = −0.59 points; 95% confidence intervals [CI], −0.83 to −0.36; p < 0.00001) and higher total effectiveness rate (risk ratio = 1.21; 95% CI, 1.15 to 1.28; p < 0.00001) when compared with standard western treatment. No serious adverse events were reported. Conclusion. Chinese herbal bath therapy may be a safe, effective, and simple alternative treatment modality for knee OA. Further rigorously designed, randomized trials are warranted. PMID:26483847

Iterative Usage of Fixed and Random Effect Models for Powerful and Efficient Genome-Wide Association Studies

PubMed Central

Liu, Xiaolei; Huang, Meng; Fan, Bin; Buckler, Edward S.; Zhang, Zhiwu

2016-01-01

False positives in a Genome-Wide Association Study (GWAS) can be effectively controlled by a fixed effect and random effect Mixed Linear Model (MLM) that incorporates population structure and kinship among individuals to adjust association tests on markers; however, the adjustment also compromises true positives. The modified MLM method, Multiple Loci Linear Mixed Model (MLMM), incorporates multiple markers simultaneously as covariates in a stepwise MLM to partially remove the confounding between testing markers and kinship. To completely eliminate the confounding, we divided MLMM into two parts: Fixed Effect Model (FEM) and a Random Effect Model (REM) and use them iteratively. FEM contains testing markers, one at a time, and multiple associated markers as covariates to control false positives. To avoid model over-fitting problem in FEM, the associated markers are estimated in REM by using them to define kinship. The P values of testing markers and the associated markers are unified at each iteration. We named the new method as Fixed and random model Circulating Probability Unification (FarmCPU). Both real and simulated data analyses demonstrated that FarmCPU improves statistical power compared to current methods. Additional benefits include an efficient computing time that is linear to both number of individuals and number of markers. Now, a dataset with half million individuals and half million markers can be analyzed within three days. PMID:26828793

Re-Examining the Association between Vitamin D and Childhood Caries

PubMed Central

Dudding, Tom; Thomas, Steve J.; Duncan, Karen; Lawlor, Debbie A.; Timpson, Nicholas J.

2015-01-01

Background Previous studies have reported an inverse association between vitamin D and childhood dental caries, but whether this is causal is unclear. Objective To determine the causal effect of circulating 25-hydroxyvitamin D concentration on dental caries experience, early caries onset and the requirement for a dental general anesthetic. Design A Mendelian randomization study was undertaken, using genetic variants known to be associated with circulating 25-hydroxyvitamin D concentrations in 5,545 European origin children from the South West of England. Data on caries and related characteristics were obtained from parental and child completed questionnaires between 38 and 91 months and clinical assessments in a random 10% sample at 31, 44 and 61 months. Results In multivariable confounder adjusted analyses no strong evidence for an association of 25-hydroxyvitamin D with caries experience or severity was found but there was evidence for an association with early caries onset, or having a general anesthetic for dental problems. In Mendelian randomization analysis the odds ratio for caries experience per 10 nmol/L increase in 25-hydroxyvitamin D was 0.93 (95% confidence interval: 0.83, 1.05; P = 0.26) and the odds ratio for dental general anaesthetic per 10 nmol/L increase in 25-hydroxyvitamin D was 0.96 (95% confidence interval: 0.75, 1.22; P = 0.72). Conclusions This Mendelian randomization study provides little evidence to support an inverse causal effect of 25-hydroxyvitamin D on dental caries. However, the estimates are imprecise and a larger study is required to refine these analyses. PMID:26692013

Basic Diagnosis and Prediction of Persistent Contrail Occurrence using High-resolution Numerical Weather Analyses/Forecasts and Logistic Regression. Part I: Effects of Random Error

NASA Technical Reports Server (NTRS)

Duda, David P.; Minnis, Patrick

2009-01-01

Straightforward application of the Schmidt-Appleman contrail formation criteria to diagnose persistent contrail occurrence from numerical weather prediction data is hindered by significant bias errors in the upper tropospheric humidity. Logistic models of contrail occurrence have been proposed to overcome this problem, but basic questions remain about how random measurement error may affect their accuracy. A set of 5000 synthetic contrail observations is created to study the effects of random error in these probabilistic models. The simulated observations are based on distributions of temperature, humidity, and vertical velocity derived from Advanced Regional Prediction System (ARPS) weather analyses. The logistic models created from the simulated observations were evaluated using two common statistical measures of model accuracy, the percent correct (PC) and the Hanssen-Kuipers discriminant (HKD). To convert the probabilistic results of the logistic models into a dichotomous yes/no choice suitable for the statistical measures, two critical probability thresholds are considered. The HKD scores are higher when the climatological frequency of contrail occurrence is used as the critical threshold, while the PC scores are higher when the critical probability threshold is 0.5. For both thresholds, typical random errors in temperature, relative humidity, and vertical velocity are found to be small enough to allow for accurate logistic models of contrail occurrence. The accuracy of the models developed from synthetic data is over 85 percent for both the prediction of contrail occurrence and non-occurrence, although in practice, larger errors would be anticipated.

Methods for increasing upper airway muscle tonus in treating obstructive sleep apnea: systematic review.

PubMed

Valbuza, Juliana Spelta; de Oliveira, Márcio Moysés; Conti, Cristiane Fiquene; Prado, Lucila Bizari F; de Carvalho, Luciane Bizari Coin; do Prado, Gilmar Fernandes

2010-12-01

Treatment of obstructive sleep apnea (OSA) using methods for increasing upper airway muscle tonus has been controversial and poorly reported. Thus, a review of the evidence is needed to evaluate the effectiveness of these methods. The design used was a systematic review of randomized controlled trials. Data sources are from the Cochrane Library, Medline, Embase and Scielo, registries of ongoing trials, theses indexed at Biblioteca Regional de Medicina/Pan-American Health Organization of the World Health Organization and the reference lists of all the trials retrieved. This was a review of randomized or quasi-randomized double-blind trials on OSA. Two reviewers independently applied eligibility criteria. One reviewer assessed study quality and extracted data, and these processes were checked by a second reviewer. The primary outcome was a decrease in the apnea/hypopnea index (AHI) of below five episodes per hour. Other outcomes were subjective sleep quality, sleep quality measured by night polysomnography, quality of life measured subjectively and adverse events associated with the treatments. Three eligible trials were included. Two studies showed improvements through the objective and subjective analyses, and one study showed improvement of snoring, but not of AHI while the subjective analyses showed no improvement. The adverse events were reported and they were not significant. There is no accepted scientific evidence that methods aiming to increase muscle tonus of the stomatognathic system are effective in reducing AHI to below five events per hour. Well-designed randomized controlled trials are needed to assess the efficacy of such methods.

Economic evaluation of an intervention program with the aim to improve at-work productivity for workers with rheumatoid arthritis.

PubMed

Noben, Cindy; Vilsteren, Myrthe van; Boot, Cécile; Steenbeek, Romy; Schaardenburg, Dirkjan van; Anema, Johannes R; Evers, Silvia; Nijhuis, Frans; Rijk, Angelique de

2017-05-25

Evaluating the cost effectiveness and cost utility of an integrated care intervention and participatory workplace intervention for workers with rheumatoid arthritis (RA) to improve their work productivity. Twelve month follow-up economic evaluation alongside a randomized controlled trial (RCT) within specialized rheumatology treatment centers. Adults diagnosed with RA between 18-64 years, in a paid job for at least eight hours per week, experiencing minor difficulties in work functioning were randomized to the intervention (n = 75) or the care-as-usual (CAU) group (n = 75). Effect outcomes were productivity and quality of life (QALYs). Costs associated with healthcare, patient and family, productivity, and intervention were calculated from a societal perspective. Cost effectiveness and cost utility were assessed to indicate the incremental costs and benefits per additional unit of effect. Subgroup and sensitivity analyses evaluated the robustness of the findings. At-work productivity loss was about 4.6 hours in the intervention group and 3.5 hours in the care as usual (CAU) group per two weeks. Differences in QALY were negligible; 0.77 for the CAU group and 0.74 for the intervention group. In total, average costs after twelve months follow-up were highest in the intervention group (€7,437.76) compared to the CAU group (€5,758.23). The cost-effectiveness and cost-utility analyses show that the intervention was less effective and (often) more expensive when compared to CAU. Sensitivity analyses supported these findings. The integrated care intervention and participatory workplace intervention for workers with RA provides gains neither in productivity at the workplace nor in quality of life. These results do not justify the additional costs.

Economic evaluation of an intervention program with the aim to improve at-work productivity for workers with rheumatoid arthritis

PubMed Central

Noben, Cindy; van Vilsteren, Myrthe; Boot, Cécile; Steenbeek, Romy; van Schaardenburg, Dirkjan; Anema, Johannes R.; Evers, Silvia; Nijhuis, Frans; de Rijk, Angelique

2017-01-01

Objectives: Evaluating the cost effectiveness and cost utility of an integrated care intervention and participatory workplace intervention for workers with rheumatoid arthritis (RA) to improve their work productivity. Methods: Twelve month follow-up economic evaluation alongside a randomized controlled trial (RCT) within specialized rheumatology treatment centers. Adults diagnosed with RA between 18-64 years, in a paid job for at least eight hours per week, experiencing minor difficulties in work functioning were randomized to the intervention (n = 75) or the care-as-usual (CAU) group (n = 75). Effect outcomes were productivity and quality of life (QALYs). Costs associated with healthcare, patient and family, productivity, and intervention were calculated from a societal perspective. Cost effectiveness and cost utility were assessed to indicate the incremental costs and benefits per additional unit of effect. Subgroup and sensitivity analyses evaluated the robustness of the findings. Results: At-work productivity loss was about 4.6 hours in the intervention group and 3.5 hours in the care as usual (CAU) group per two weeks. Differences in QALY were negligible; 0.77 for the CAU group and 0.74 for the intervention group. In total, average costs after twelve months follow-up were highest in the intervention group (€7,437.76) compared to the CAU group (€5,758.23). The cost-effectiveness and cost-utility analyses show that the intervention was less effective and (often) more expensive when compared to CAU. Sensitivity analyses supported these findings. Discussion: The integrated care intervention and participatory workplace intervention for workers with RA provides gains neither in productivity at the workplace nor in quality of life. These results do not justify the additional costs. PMID:28381814

Effects and moderators of psychosocial interventions on quality of life, and emotional and social function in patients with cancer: An individual patient data meta‐analysis of 22 RCTs

PubMed Central

Kalter, J.; Verdonck‐de Leeuw, I.M.; Sweegers, M.G.; Aaronson, N.K.; Jacobsen, P.B.; Newton, R.U.; Courneya, K.S.; Aitken, J.F.; Armes, J.; Arving, C.; Boersma, L.J.; Braamse, A.M.J.; Brandberg, Y.; Chambers, S.K.; Dekker, J.; Ell, K.; Ferguson, R.J.; Gielissen, M.F.M.; Glimelius, B.; Goedendorp, M.M.; Graves, K.D.; Heiney, S.P.; Horne, R.; Hunter, M.S.; Johansson, B.; Kimman, M.L.; Knoop, H.; Meneses, K.; Northouse, L.L.; Oldenburg, H.S.; Prins, J.B.; Savard, J.; van Beurden, M.; van den Berg, S.W.; Brug, J.

2018-01-01

Abstract Objective This individual patient data (IPD) meta‐analysis aimed to evaluate the effects of psychosocial interventions (PSI) on quality of life (QoL), emotional function (EF), and social function (SF) in patients with cancer, and to study moderator effects of demographic, clinical, personal, and intervention‐related characteristics. Methods Relevant studies were identified via literature searches in 4 databases. We pooled IPD from 22 (n = 4217) of 61 eligible randomized controlled trials. Linear mixed‐effect model analyses were used to study intervention effects on the post‐intervention values of QoL, EF, and SF (z‐scores), adjusting for baseline values, age, and cancer type. We studied moderator effects by testing interactions with the intervention for demographic, clinical, personal, and intervention‐related characteristics, and conducted subsequent stratified analyses for significant moderator variables.Results: PSI significantly improved QoL (β = 0.14,95%CI = 0.06;0.21), EF (β = 0.13,95%CI = 0.05;0.20), and SF (β = 0.10,95%CI = 0.03;0.18). Significant differences in effects of different types of PSI were found, with largest effects of psychotherapy. The effects of coping skills training were moderated by age, treatment type, and targeted interventions. Effects of psychotherapy on EF may be moderated by cancer type, but these analyses were based on 2 randomized controlled trials with small sample sizes of some cancer types. Conclusions PSI significantly improved QoL, EF, and SF, with small overall effects. However, the effects differed by several demographic, clinical, personal, and intervention‐related characteristics. Our study highlights the beneficial effects of coping skills training in patients treated with chemotherapy, the importance of targeted interventions, and the need of developing interventions tailored to the specific needs of elderly patients. PMID:29361206

Fiber for the treatment of hemorrhoids complications: a systematic review and meta-analysis.

PubMed

Alonso-Coello, Pablo; Mills, Ed; Heels-Ansdell, Diane; López-Yarto, Maite; Zhou, Qi; Johanson, John F; Guyatt, Gordon

2006-01-01

To evaluate the impact of laxatives on a wide range of symptoms in patients with symptomatic hemorrhoids. We searched using the following sources: MEDLINE, EMBASE, CINAHL and CENTRAL, BIOSIS, AMED, Papers First and Proceedings; study authors, industry, and experts in the field. We included all published and unpublished parallel group randomized controlled trials comparing any type of laxative to placebo or no therapy in patients with symptomatic hemorrhoids. Two reviewers independently screened studies for inclusion, retrieved all potentially relevant studies, and extracted data on study population, intervention, prespecified outcomes, and methodology. Seven trials randomized 378 patients to fiber or a nonfiber control. Studies were of moderate quality for most outcomes. Meta-analyses using random effects models suggested that fiber has an apparent beneficial effect. The risk of not improving/persisting symptoms decreased by 47% in the fiber group (RR = 0.53, 95% CI 0.38-0.73) and the risk of bleeding by 50% (RR = 0.50, 95% CI 0.28-0.89). Studies with multiple follow-ups, usually at 6 wk and at 3 months, showed consistent results over time. Results are also compatible with large treatment effects in prolapse, pain, and itching, but even in the pooled analyses confidence intervals were wide and compatible with no effect (RR = 0.79, 95% CI 0.37-1.67; RR = 0.33, 95% CI 0.07-1.65; and RR = 0.71, 95% CI 0.24-2.10, respectively). One study suggested a decrease in recurrence. Results showed a nonsignificant trend toward increases in mild adverse events in the fiber group (RR = 6.0, 95% CI 0.57-64.8). Trials of fiber show a consistent beneficial effect for symptoms and bleeding in the treatment of symptomatic hemorrhoids.

Home-based balance training using the Wii balance board: a randomized, crossover pilot study in multiple sclerosis.

PubMed

Prosperini, Luca; Fortuna, Deborah; Giannì, Costanza; Leonardi, Laura; Marchetti, Maria Rita; Pozzilli, Carlo

2013-01-01

To evaluate the effectiveness of a home-based rehabilitation of balance using the Nintendo Wii Balance Board System (WBBS) in patients affected by multiple sclerosis (MS). In this 24-week, randomized, 2-period crossover pilot study, 36 patients having an objective balance disorder were randomly assigned in a 1:1 ratio to 2 counterbalanced arms. Group A started a 12-week period of home-based WBBS training followed by a 12-week period without any intervention; group B received the treatment in reverse order. As endpoints, we considered the mean difference (compared with baseline) in force platform measures (i.e., the displacement of body center of pressure in 30 seconds), 4-step square test (FSST), 25-foot timed walking test (25-FWT), and 29-item MS Impact Scale (MSIS-29), as evaluated after 12 weeks and at the end of the 24-week study period. The 2 groups did not differ in baseline characteristics. Repeated-measures analyses of variance showed significant time × treatment effects, indicating that WBBS was effective in ameliorating force platform measures (F = 4.608, P = .016), FSST (F = 3.745, P = .034), 25-FWT (F = 3.339, P = .048), and MSIS-29 (F = 4.282, P = .023). Five adverse events attributable to the WBSS training (knee or low back pain) were recorded, but only 1 patient had to retire from the study. A home-based WBBS training might potentially provide an effective, engaging, balance rehabilitation solution for people with MS. However, the risk of WBBS training-related injuries should be carefully balanced with benefits. Further studies, including cost-effectiveness analyses, are warranted to establish whether WBBS may be useful in the home setting.

Internet-Delivered Cognitive Behavior Therapy for Adolescents With Irritable Bowel Syndrome: A Randomized Controlled Trial.

PubMed

Bonnert, Marianne; Olén, Ola; Lalouni, Maria; Benninga, Marc A; Bottai, Matteo; Engelbrektsson, Johanna; Hedman, Erik; Lenhard, Fabian; Melin, Bo; Simrén, Magnus; Vigerland, Sarah; Serlachius, Eva; Ljótsson, Brjánn

2017-01-01

Few treatments have been able to effectively manage pediatric irritable bowel syndrome (IBS). Internet-delivered cognitive behavior therapy (Internet-CBT) based on exposure for abdominal symptoms is effective for adult IBS. The objective of this study was to evaluate the efficacy of Internet-CBT based on behavioral exposure for adolescents with IBS. Adolescents with IBS fulfilling the Rome III criteria were randomized to either Internet-CBT or a wait-list control. The Internet-CBT was a 10-week intervention where the main component was exposure to IBS symptoms by reduction of avoidance of abdominal symptoms and instead stepwise provocation of symptoms. The primary outcome was total score on Gastrointestinal Symptoms Rating Scale for IBS (GSRS-IBS). Secondary outcomes included adolescent- and parent-rated quality of life and parent-rated gastrointestinal symptoms. Difference between groups was assessed from pretreatment to posttreatment and the Internet-CBT group was also evaluated at 6 months after treatment completion. A total of 101 adolescents with IBS (13-17 years of age) were included in this study. Dropout rates were low (6%) and all randomized patients were included in intent-to-treat analyses based on mixed effects models. Analyses showed a significant larger pretreatment to posttreatment change on the primary outcome GSRS-IBS (B=-6.42, P=0.006, effect size Cohen's d=0.45, 95% confidence interval (0.12, 0.77)) and on almost all secondary outcomes for the Internet-CBT group compared with the control group. After 6 months, the results were stable or significantly improved. Internet-CBT based on exposure exercises for adolescents with IBS can effectively improve gastrointestinal symptoms and quality of life.

Effects of condom social marketing on condom use in developing countries: a systematic review and meta-analysis, 1990-2010.

PubMed

Sweat, Michael D; Denison, Julie; Kennedy, Caitlin; Tedrow, Virginia; O'Reilly, Kevin

2012-08-01

To examine the relationship between condom social marketing programmes and condom use. Standard systematic review and meta-analysis methods were followed. The review included studies of interventions in which condoms were sold, in which a local brand name(s) was developed for condoms, and in which condoms were marketed through a promotional campaign to increase sales. A definition of intervention was developed and standard inclusion criteria were followed in selecting studies. Data were extracted from each eligible study, and a meta-analysis of the results was carried out. Six studies with a combined sample size of 23,048 met the inclusion criteria. One was conducted in India and five in sub-Saharan Africa. All studies were cross-sectional or serial cross-sectional. Three studies had a comparison group, although all lacked equivalence in sociodemographic characteristics across study arms. All studies randomly selected participants for assessments, although none randomly assigned participants to intervention arms. The random-effects pooled odds ratio for condom use was 2.01 (95% confidence interval, CI: 1.42-2.84) for the most recent sexual encounter and 2.10 (95% CI: 1.51-2.91) for a composite of all condom use outcomes. Tests for heterogeneity yielded significant results for both meta-analyses. The evidence base for the effect of condom social marketing on condom use is small because few rigorous studies have been conducted. Meta-analyses showed a positive and statistically significant effect on increasing condom use, and all individual studies showed positive trends. The cumulative effect of condom social marketing over multiple years could be substantial. We strongly encourage more evaluations of these programmes with study designs of high rigour.

Effect of patient navigation on colorectal cancer screening in a community-based randomized controlled trial of urban African American adults

PubMed Central

Phelan-Emrick, Darcy F.; Pollack, Craig E.; Markakis, Diane; Wenzel, Jennifer; Ahmed, Saifuddin; Garza, Mary A.; Shapiro, Gary R.; Bone, Lee R.; Johnson, Lawrence B.; Ford, Jean G.

2015-01-01

Purpose In recent years, colorectal cancer (CRC) screening rates have increased steadily in the USA, though racial and ethnic disparities persist. In a community-based randomized controlled trial, we investigated the effect of patient navigation on increasing CRC screening adherence among older African Americans. Methods Participants in the Cancer Prevention and Treatment Demonstration were randomized to either the control group, receiving only printed educational materials (PEM), or the intervention arm where they were assigned a patient navigator in addition to PEM. Navigators assisted participants with identifying and overcoming screening barriers. Logistic regression analyses were used to assess the effect of patient navigation on CRC screening adherence. Up-to-date with screening was defined as self-reported receipt of colonoscopy/sigmoidoscopy in the previous 10 years or fecal occult blood testing (FOBT) in the year prior to the exit interview. Results Compared with controls, the intervention group was more likely to report being up-to-date with CRC screening at the exit interview (OR 1.55, 95 % CI 1.07–2.23), after adjusting for select demographics. When examining the screening modalities separately, the patient navigator increased screening for colonoscopy/sigmoidoscopy (OR 1.53, 95 % CI 1.07–2.19), but not FOBT screening. Analyses of moderation revealed stronger effects of navigation among participants 65–69 years and those with an adequate health literacy level. Conclusions In a population of older African Americans adults, patient navigation was effective in increasing the likelihood of CRC screening. However, more intensive navigation may be necessary for adults over 70 years and individuals with low literacy levels. PMID:25516073

Effect of patient navigation on colorectal cancer screening in a community-based randomized controlled trial of urban African American adults.

PubMed

Horne, Hisani N; Phelan-Emrick, Darcy F; Pollack, Craig E; Markakis, Diane; Wenzel, Jennifer; Ahmed, Saifuddin; Garza, Mary A; Shapiro, Gary R; Bone, Lee R; Johnson, Lawrence B; Ford, Jean G

2015-02-01

In recent years, colorectal cancer (CRC) screening rates have increased steadily in the USA, though racial and ethnic disparities persist. In a community-based randomized controlled trial, we investigated the effect of patient navigation on increasing CRC screening adherence among older African Americans. Participants in the Cancer Prevention and Treatment Demonstration were randomized to either the control group, receiving only printed educational materials (PEM), or the intervention arm where they were assigned a patient navigator in addition to PEM. Navigators assisted participants with identifying and overcoming screening barriers. Logistic regression analyses were used to assess the effect of patient navigation on CRC screening adherence. Up-to-date with screening was defined as self-reported receipt of colonoscopy/sigmoidoscopy in the previous 10 years or fecal occult blood testing (FOBT) in the year prior to the exit interview. Compared with controls, the intervention group was more likely to report being up-to-date with CRC screening at the exit interview (OR 1.55, 95 % CI 1.07-2.23), after adjusting for select demographics. When examining the screening modalities separately, the patient navigator increased screening for colonoscopy/sigmoidoscopy (OR 1.53, 95 % CI 1.07-2.19), but not FOBT screening. Analyses of moderation revealed stronger effects of navigation among participants 65-69 years and those with an adequate health literacy level. In a population of older African Americans adults, patient navigation was effective in increasing the likelihood of CRC screening. However, more intensive navigation may be necessary for adults over 70 years and individuals with low literacy levels.

Effects of condom social marketing on condom use in developing countries: a systematic review and meta-analysis, 1990–2010

PubMed Central

Denison, Julie; Kennedy, Caitlin; Tedrow, Virginia; O'Reilly, Kevin

2012-01-01

Abstract Objective To examine the relationship between condom social marketing programmes and condom use. Methods Standard systematic review and meta-analysis methods were followed. The review included studies of interventions in which condoms were sold, in which a local brand name(s) was developed for condoms, and in which condoms were marketed through a promotional campaign to increase sales. A definition of intervention was developed and standard inclusion criteria were followed in selecting studies. Data were extracted from each eligible study, and a meta-analysis of the results was carried out. Findings Six studies with a combined sample size of 23 048 met the inclusion criteria. One was conducted in India and five in sub-Saharan Africa. All studies were cross-sectional or serial cross-sectional. Three studies had a comparison group, although all lacked equivalence in sociodemographic characteristics across study arms. All studies randomly selected participants for assessments, although none randomly assigned participants to intervention arms. The random-effects pooled odds ratio for condom use was 2.01 (95% confidence interval, CI: 1.42–2.84) for the most recent sexual encounter and 2.10 (95% CI: 1.51–2.91) for a composite of all condom use outcomes. Tests for heterogeneity yielded significant results for both meta-analyses. Conclusion The evidence base for the effect of condom social marketing on condom use is small because few rigorous studies have been conducted. Meta-analyses showed a positive and statistically significant effect on increasing condom use, and all individual studies showed positive trends. The cumulative effect of condom social marketing over multiple years could be substantial. We strongly encourage more evaluations of these programmes with study designs of high rigour. PMID:22893745

Meta-regression analyses, meta-analyses, and trial sequential analyses of the effects of supplementation with beta-carotene, vitamin A, and vitamin E singly or in different combinations on all-cause mortality: do we have evidence for lack of harm?

PubMed

Bjelakovic, Goran; Nikolova, Dimitrinka; Gluud, Christian

2013-01-01

Evidence shows that antioxidant supplements may increase mortality. Our aims were to assess whether different doses of beta-carotene, vitamin A, and vitamin E affect mortality in primary and secondary prevention randomized clinical trials with low risk of bias. The present study is based on our 2012 Cochrane systematic review analyzing beneficial and harmful effects of antioxidant supplements in adults. Using random-effects meta-analyses, meta-regression analyses, and trial sequential analyses, we examined the association between beta-carotene, vitamin A, and vitamin E, and mortality according to their daily doses and doses below and above the recommended daily allowances (RDA). We included 53 randomized trials with low risk of bias (241,883 participants, aged 18 to 103 years, 44.6% women) assessing beta-carotene, vitamin A, and vitamin E. Meta-regression analysis showed that the dose of vitamin A was significantly positively associated with all-cause mortality. Beta-carotene in a dose above 9.6 mg significantly increased mortality (relative risk (RR) 1.06, 95% confidence interval (CI) 1.02 to 1.09, I(2) = 13%). Vitamin A in a dose above the RDA (> 800 µg) did not significantly influence mortality (RR 1.08, 95% CI 0.98 to 1.19, I(2) = 53%). Vitamin E in a dose above the RDA (> 15 mg) significantly increased mortality (RR 1.03, 95% CI 1.00 to 1.05, I(2) = 0%). Doses below the RDAs did not affect mortality, but data were sparse. Beta-carotene and vitamin E in doses higher than the RDA seem to significantly increase mortality, whereas we lack information on vitamin A. Dose of vitamin A was significantly associated with increased mortality in meta-regression. We lack information on doses below the RDA. All essential compounds to stay healthy cannot be synthesized in our body. Therefore, these compounds must be taken through our diet or obtained in other ways [1]. Oxidative stress has been suggested to cause a variety of diseases [2]. Therefore, it is speculated that antioxidant supplements could have a potential role in preventing diseases and death. Despite the fact that a normal diet in high-income countries may provide sufficient amounts of antioxidants [3,4], more than one third of adults regularly take antioxidant supplements [5,6].

Genetic analyses of partial egg production in Japanese quail using multi-trait random regression models.

PubMed

Karami, K; Zerehdaran, S; Barzanooni, B; Lotfi, E

2017-12-01

1. The aim of the present study was to estimate genetic parameters for average egg weight (EW) and egg number (EN) at different ages in Japanese quail using multi-trait random regression (MTRR) models. 2. A total of 8534 records from 900 quail, hatched between 2014 and 2015, were used in the study. Average weekly egg weights and egg numbers were measured from second until sixth week of egg production. 3. Nine random regression models were compared to identify the best order of the Legendre polynomials (LP). The most optimal model was identified by the Bayesian Information Criterion. A model with second order of LP for fixed effects, second order of LP for additive genetic effects and third order of LP for permanent environmental effects (MTRR23) was found to be the best. 4. According to the MTRR23 model, direct heritability for EW increased from 0.26 in the second week to 0.53 in the sixth week of egg production, whereas the ratio of permanent environment to phenotypic variance decreased from 0.48 to 0.1. Direct heritability for EN was low, whereas the ratio of permanent environment to phenotypic variance decreased from 0.57 to 0.15 during the production period. 5. For each trait, estimated genetic correlations among weeks of egg production were high (from 0.85 to 0.98). Genetic correlations between EW and EN were low and negative for the first two weeks, but they were low and positive for the rest of the egg production period. 6. In conclusion, random regression models can be used effectively for analysing egg production traits in Japanese quail. Response to selection for increased egg weight would be higher at older ages because of its higher heritability and such a breeding program would have no negative genetic impact on egg production.

Health Promotion and Healthier Products Increase Vending Purchases: A Randomized Factorial Trial.

PubMed

Hua, Sophia V; Kimmel, Lisa; Van Emmenes, Michael; Taherian, Rafi; Remer, Geraldine; Millman, Adam; Ickovics, Jeannette R

2017-07-01

The current food environment has a high prevalence of nutrient-sparse foods and beverages, most starkly seen in vending machine offerings. There are currently few studies that explore different interventions that might lead to healthier vending machine purchases. To examine how healthier product availability, price reductions, and/or promotional signs affect sales and revenue of snack and beverage vending machines. A 2×2×2 factorial randomized controlled trial was conducted. Students, staff, and employees on a university campus. All co-located snack and beverage vending machines (n=56, 28 snack and 28 beverage) were randomized into one of eight conditions: availability of healthier products and/or 25% price reduction for healthier items and/or promotional signs on machines. Aggregate sales and revenue data for the 5-month study period (February to June 2015) were compared with data from the same months 1 year prior. Analyses were conducted July 2015. The change in units sold and revenue between February through June 2014 and 2015. Linear regression models (main effects and interaction effects) and t test analyses were performed. The interaction between healthier product guidelines and promotional signs in snack vending machines documented increased revenue (P<0.05). Beverage machines randomized to meet healthier product guidelines documented increased units sold (P<0.05) with no revenue change. Price reductions alone had no effect, nor were there any effects for the three-way interaction of the factors. Examining top-selling products for all vending machines combined, pre- to postintervention, we found an overall shift to healthier purchasing. When healthier vending snacks are available, promotional signs are also important to ensure consumers purchase those items in greater amounts. Mitigating potential loss in profits is essential for sustainability of a healthier food environment. Copyright © 2017 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

The effect of concentrated bone marrow aspirate in operative treatment of fifth metatarsal stress fractures; a double-blind randomized controlled trial.

PubMed

Weel, Hanneke; Mallee, Wouter H; van Dijk, C Niek; Blankevoort, Leendert; Goedegebuure, Simon; Goslings, J Carel; Kennedy, John G; Kerkhoffs, Gino M M J

2015-08-20

Fifth metatarsal (MT-V) stress fractures often exhibit delayed union and are high-risk fractures for non-union. Surgical treatment, currently considered as the gold standard, does not give optimal results, with a mean time to fracture union of 12-18 weeks. In recent studies, the use of bone marrow cells has been introduced to accelerate healing of fractures with union problems. The aim of this randomized trial is to determine if operative treatment of MT-V stress fractures with use of concentrated blood and bone marrow aspirate (cB + cBMA) is more effective than surgery alone. We hypothesize that using cB + cBMA in the operative treatment of MT-V stress fractures will lead to an earlier fracture union. A prospective, double-blind, randomized controlled trial (RCT) will be conducted in an academic medical center in the Netherlands. Ethics approval is received. 50 patients will be randomized to either operative treatment with cB + cBMA, harvested from the iliac crest, or operative treatment without cB + cBMA but with a sham-treatment of the iliac crest. The fracture fixation is the same in both groups, as is the post-operative care.. Follow up will be one year. The primary outcome measure is time to union in weeks on X-ray. Secondary outcome measures are time to resumption of work and sports, functional outcomes (SF-36, FAOS, FAAM), complication rate, composition of osteoprogenitors in cB + cBMA and cost-effectiveness. Furthermore, a bone biopsy is taken from every stress fracture and analysed histologically to determine the stage of the stress fracture. The difference in primary endpoint between the two groups is analysed using student's t-test or equivalent. This trial will likely provide level-I evidence on the effectiveness of cB + cBMA in the operative treatment of MT-V stress fractures. Netherlands Trial Register (reg.nr NTR4377 ).

The role of reflection in the effects of community service on adolescent development: a meta-analysis.

PubMed

van Goethem, Anne; van Hoof, Anne; Orobio de Castro, Bram; Van Aken, Marcel; Hart, Daniel

2014-01-01

This meta-analysis assessed the effect of community service on adolescent development and the moderation of this effect by reflection, community service, and adolescent characteristics to explicate the mechanisms underlying community service effects. Random effects analyses, based on 49 studies (24,477 participants, 12-20 years old), revealed that community service had positive effects on academic, personal, social, and civic outcomes. Moderation analyses indicated that reflection was essential; the effect for studies that include reflection was substantial (mean ES = .41) while community service in the absence of reflection yielded negligible benefits (mean ES = .05). Effects increased when studies include more frequent reflection and community service, reflection on academic content, and older adolescents. These findings have implications for understanding and improving community service. © 2014 The Authors. Child Development © 2014 Society for Research in Child Development, Inc.

Role of Acupuncture in the Treatment or Prevention of Migraine, Tension-Type Headache, or Chronic Headache Disorders.

PubMed

Coeytaux, Remy R; Befus, Deanna

2016-07-01

To summarize the current evidence that evaluates the effectiveness of acupuncture for the treatment or prevention of migraine, tension-type headache, and chronic headache disorders. Findings from selected systematic reviews and meta-analyses are summarized. Recently published systematic reviews and meta-analyses demonstrate that acupuncture is associated with improved clinical outcomes compared to routine care only, medical management, and sham acupuncture 2 months after randomization. The evidence in support of acupuncture's comparative effectiveness at longer follow-up periods is mixed. Cost effectiveness analyses conducted in the United Kingdom and Germany suggest that acupuncture is a cost-effective treatment option in those countries. There are few or no cost-effectiveness studies of acupuncture in the United States. This brief review of the current, published evidence does not include a discussion of potential risks or adverse events associated with acupuncture. There is also the question of the extent to which placebo effects might contribute to acupuncture's clinical effectiveness. From a purely comparative effectiveness perspective, however, the evidence from clinical trials and meta-analyses makes a compelling case in support of a potentially important role for acupuncture as part of a treatment plan for patients with migraine, tension-type headache, and several different types of chronic headache disorders. © 2016 American Headache Society.

A Randomized Control Intervention Investigating the Effects of Acute Exercise on Emotional Regulation.

PubMed

Edwards, Meghan K; Rhodes, Ryan E; Loprinzi, Paul D

2017-09-01

Exercise may help to cope with hectic or demanding events after a stressful situation occurs. Limited research has evaluated whether exercise, prior to a stressor, helps to facilitate subsequent emotional regulation. This pilot study addresses this novel paradigm. We employed a randomized controlled trial evaluating the effects of acute exercise on emotional regulation. Participants were randomly assigned to stretch (control group, N = 10), walk (N = 9), or jog (N = 8) for 15-minutes, after which they were exposed to a film clip intended to elicit a negative emotional response. Participants' emotions were monitored before and during exercise, as well as after the film clip. Emotional responses were evaluated using the Exercise Induced Feeling Inventory and Affective Circumplex Scale. A group x time splitplot interaction effect was significant for anger (p = .046) and anxiousness (p = .038). Follow-up analyses showed that only the stretching group (p = .048) had a significantly increased anger score from baseline to post-film clip, suggesting a protective emotional effect from walking and jogging. Exercise was effective in regulating anger and anxiousness after a stressful event. These findings provide evidence for potential preventive effects of exercise in facilitating emotional regulation.

Therapist Adherence and Competence with Manualized Cognitive-Behavioral Therapy for PTSD Delivered via Videoconferencing Technology

ERIC Educational Resources Information Center

Frueh, B. Christopher; Monnier, Jeannine; Grubaugh, Anouk L.; Elhai, Jon D.; Yim, Eunsil; Knapp, Rebecca

2007-01-01

Using secondary analyses from a randomized trial comparing the effectiveness of manualized cognitive-behavioral therapy for posttraumatic stress disorder, we compared ratings of therapist competency and adherence between two service delivery modes: telepsychiatry (TP) and same room (SR). Patients were 38 male treatment-seeking veterans recruited…

Preventing Adolescents' Externalizing and Internalizing Symptoms: Effects of the Penn Resiliency Program

ERIC Educational Resources Information Center

Cutuli, J. J.; Gillham, Jane E.; Chaplin, Tara M.; Reivich, Karen J.; Seligman, Martin E. P.; Gallop, Robert J.; Abenavoli, Rachel M.; Freres, Derek R.

2013-01-01

This study reports secondary outcome analyses from a past study of the Penn Resiliency Program (PRP), a cognitive-behavioral depression prevention program for middle-school aged children. Middle school students (N = 697) were randomly assigned to PRP, PEP (an alternate intervention), or control conditions. Gillham et al., (2007) reported analyses…

The Richer, the Happier? An Empirical Investigation in Selected European Countries

ERIC Educational Resources Information Center

Seghieri, Chiara; Desantis, Gustavo; Tanturri, Maria Letizia

2006-01-01

This study analyses the relationship between subjective and objective measures of well-being in selected European countries using the data of the European Community Household Panel (ECHP). In the first part of the paper, we develop a random-effect ordered probit model, separately for each country, relating the subjective measure of income…

Student-Produced Videos Can Enhance Engagement and Learning in the Online Environment

ERIC Educational Resources Information Center

Stanley, Denise; Zhang, Yi

2018-01-01

Student engagement in online learning remains a challenge for the design of effective coursework. Additionally, few analyses have focused on student-produced activities in the online mode or upon how such class activity affects student subgroups differently. We conducted a randomized design experiment with student video production at a large…

Applying Randomized Controlled Trials and Systematic Reviews in Social Work Research

ERIC Educational Resources Information Center

Soydan, Haluk

2008-01-01

This article elaborates on the centrality of interventions for social work practice and the importance of understanding the effects of interventions for a more efficient, harmless, transparent, and ethical social work practice. Low-bias research designs and meta-analyses are important means of generating the best possible evidence on what works in…

Aspirin Metabolomics in Colorectal Cancer Chemoprevention | Division of Cancer Prevention

Cancer.gov

Substantial evidence supports the effectiveness of aspirin for cancer chemoprevention in addition to its well-established role in cardiovascular protection. In recent meta-analyses of randomized controlled trials in humans, daily aspirin use reduced incidence, metastasis and mortality from several common types of cancer, especially colorectal cancer. The mechanism(s) by which

The Efficacy of Adapted MBCT on Core Symptoms and Executive Functioning in Adults With ADHD: A Preliminary Randomized Controlled Trial.

PubMed

Hepark, Sevket; Janssen, Lotte; de Vries, Alicia; Schoenberg, Poppy L A; Donders, Rogier; Kan, Cornelis C; Speckens, Anne E M

2015-11-20

The aim of this study was to examine the effectiveness of mindfulness as a treatment for adults diagnosed with ADHD. A 12-week-adapted mindfulness-based cognitive therapy (MBCT) program is compared with a waiting list (WL) group. Adults with ADHD were randomly allocated to MBCT (n = 55) or waitlist (n = 48). Outcome measures included investigator-rated ADHD symptoms (primary), self-reported ADHD symptoms, executive functioning, depressive and anxiety symptoms, patient functioning, and mindfulness skills. MBCT resulted in a significant reduction of ADHD symptoms, both investigator-rated and self-reported, based on per-protocol and intention-to-treat analyses. Significant improvements in executive functioning and mindfulness skills were found. Additional analyses suggested that the efficacy of MBCT in reducing ADHD symptoms and improving executive functioning is partially mediated by an increase in the mindfulness skill "Act With Awareness." No improvements were observed for depressive and anxiety symptoms, and patient functioning. This study provides preliminary support for the effectiveness of MBCT for adults with ADHD. © The Author(s) 2015.

Mediation Analysis of the Efficacy of the Eban HIV/STD Risk-Reduction Intervention for African American HIV Serodiscordant Couples.

PubMed

El-Bassel, Nabila; Jemmott, John B; Bellamy, Scarlett L; Pequegnat, Willo; Wingood, Gina M; Wyatt, Gail E; Landis, J Richard; Remien, Robert H

2016-06-01

Targeting couples is a promising behavioral HIV risk-reduction strategy, but the mechanisms underlying the effects of such interventions are unknown. We report secondary analyses testing whether Social-Cognitive-Theory variables mediated the Eban HIV-risk-reduction intervention's effects on condom-use outcomes. In a multisite randomized controlled trial conducted in four US cities, 535 African American HIV-serodiscordant couples were randomized to the Eban HIV risk-reduction intervention or attention-matched control intervention. Outcomes were proportion condom-protected sex, consistent condom use, and frequency of unprotected sex measured pre-, immediately post-, and 6 and 12 months post-intervention. Potential mediators included Social-Cognitive-Theory variables: outcome expectancies and self-efficacy. Mediation analyses using the product-of-coefficients approach in a generalized-estimating-equations framework revealed that condom-use outcome expectancy, partner-reaction outcome expectancy, intention, self-efficacy, and safer-sex communication improved post-intervention and mediated intervention-induced improvements in condom-use outcomes. These findings underscore the importance of targeting outcome expectancies, self-efficacy, and safer-sex communication in couples-level HIV risk-reduction interventions.

A structured framework for assessing sensitivity to missing data assumptions in longitudinal clinical trials.

PubMed

Mallinckrodt, C H; Lin, Q; Molenberghs, M

2013-01-01

The objective of this research was to demonstrate a framework for drawing inference from sensitivity analyses of incomplete longitudinal clinical trial data via a re-analysis of data from a confirmatory clinical trial in depression. A likelihood-based approach that assumed missing at random (MAR) was the primary analysis. Robustness to departure from MAR was assessed by comparing the primary result to those from a series of analyses that employed varying missing not at random (MNAR) assumptions (selection models, pattern mixture models and shared parameter models) and to MAR methods that used inclusive models. The key sensitivity analysis used multiple imputation assuming that after dropout the trajectory of drug-treated patients was that of placebo treated patients with a similar outcome history (placebo multiple imputation). This result was used as the worst reasonable case to define the lower limit of plausible values for the treatment contrast. The endpoint contrast from the primary analysis was - 2.79 (p = .013). In placebo multiple imputation, the result was - 2.17. Results from the other sensitivity analyses ranged from - 2.21 to - 3.87 and were symmetrically distributed around the primary result. Hence, no clear evidence of bias from missing not at random data was found. In the worst reasonable case scenario, the treatment effect was 80% of the magnitude of the primary result. Therefore, it was concluded that a treatment effect existed. The structured sensitivity framework of using a worst reasonable case result based on a controlled imputation approach with transparent and debatable assumptions supplemented a series of plausible alternative models under varying assumptions was useful in this specific situation and holds promise as a generally useful framework. Copyright © 2012 John Wiley & Sons, Ltd.

Effect of coenzyme Q10 supplementation on heart failure: a meta-analysis123

PubMed Central

Thompson-Paul, Angela M; Bazzano, Lydia A

2013-01-01

Background: Coenzyme Q10 (CoQ10; also called ubiquinone) is an antioxidant that has been postulated to improve functional status in congestive heart failure (CHF). Several randomized controlled trials have examined the effects of CoQ10 on CHF with inconclusive results. Objective: The objective of this meta-analysis was to evaluate the impact of CoQ10 supplementation on the ejection fraction (EF) and New York Heart Association (NYHA) functional classification in patients with CHF. Design: A systematic review of the literature was conducted by using databases including MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and manual examination of references from selected studies. Studies included were randomized controlled trials of CoQ10 supplementation that reported the EF or NYHA functional class as a primary outcome. Information on participant characteristics, trial design and duration, treatment, dose, control, EF, and NYHA classification were extracted by using a standardized protocol. Results: Supplementation with CoQ10 resulted in a pooled mean net change of 3.67% (95% CI: 1.60%, 5.74%) in the EF and −0.30 (95% CI: −0.66, 0.06) in the NYHA functional class. Subgroup analyses showed significant improvement in EF for crossover trials, trials with treatment duration ≤12 wk in length, studies published before 1994, and studies with a dose ≤100 mg CoQ10/d and in patients with less severe CHF. These subgroup analyses should be interpreted cautiously because of the small number of studies and patients included in each subgroup. Conclusions: Pooled analyses of available randomized controlled trials suggest that CoQ10 may improve the EF in patients with CHF. Additional well-designed studies that include more diverse populations are needed. PMID:23221577

Meta-analyses of mood stabilizers, antidepressants and antipsychotics in the treatment of borderline personality disorder: effectiveness for depression and anger symptoms.

PubMed

Mercer, Deanna; Douglass, Alan B; Links, Paul S

2009-04-01

The objective of our study was to complete separate meta-analyses of randomized controlled trials of mood stabilizers, antidepressants and antipsychotics to determine whether these medications are efficacious for depression and anger symptoms in borderline personality disorder (BPD). Studies were obtained from OVID Medline, Cochrane Central Register of Controlled Trials, and PsychInfo. References of all original papers and reviews were searched for additional studies. Index terms included: BPD, randomized controlled trials, drug therapy, medication, and treatment. Studies were included if they were randomized double-blind placebo-controlled trials, published in a peer reviewed journal, had a majority of patients with BPD or included patients with BPD where anger was a target of treatment. Preference was given to studies using outcome measures that were well known, validated, objective, and based on intent-to-treat data. Where available, measures of anger that incorporated verbal and other indirect forms of aggression were utilized. The StatsDirect meta-analysis program was used to calculate an effect size and 95% confidence interval for each study. Mood stabilizers, with the exception of divalproic acid, were found to have a large pooled effect size (-1.75, 95% CI = -2.77 to -0.74) for anger. Divalproic acid and carbamazepine had a moderate effect on depression. Antidepressants had a moderate effect on anger reduction, but a small effect on depression. Antipsychotics had a moderate effect on anger; however aripiprazole had a much larger effect-size than other antipsychotics. Antipsychotics did not have an effect for depression. Sources of variation between studies included length of treatment (5-24 weeks), drop out rates (5% to 65%), proportion of patients in psychotherapy (0-100%) and with comorbid mood disorders (0-100%). Unfortunately most studies excluded patients with alcohol and substance abuse, suicidality, and self-harm behaviors. This may limit the ability to generalize our findings to usual clinical practice.

Treatment effects of fixed functional appliances in patients with Class II malocclusion: a systematic review and meta-analysis

PubMed Central

Zymperdikas, Vasileios F.; Koretsi, Vasiliki; Papageorgiou, Spyridon N.

2016-01-01

Summary Objective: To assess the treatment effects of fixed functional appliances (FFAs) in treated versus untreated Class II patients by means of lateral cephalometric radiographs. Search methods: Unrestricted electronic search of 18 databases and additional manual searches up to October 2014. Selection criteria: Prospective randomized and non-randomized controlled trials reporting on cephalometric angular measurements of Class II patients treated with FFAs and their matched untreated controls. Data collection and analysis: Skeletal, dental, and soft tissue cephalometric data were annualized and stratified according to the time of evaluation in effects. Following risk of bias evaluation, the mean differences (MDs) and 95 % confidence intervals (CIs) were calculated with random-effects models. Patient- and appliance-related subgroup analyses and sensitivity analyses were performed with mixed-effects models. Results: Nine studies were included (244 patients; mean age: 13.5 years and 174 untreated controls; mean age: 12.8 years) reporting on cephalometric effects directly after the removal of FFAs. FFAs were found to induce a small reduction of SNA angle (MD = −0.83 degree/year, 95 % CI: −1.17 to −0.48), a small increase of SNB angle (MD = 0.87 degree/year, 95 % CI: 0.30–1.43), and moderate decrease of ANB angle (MD = −1.74 degree/year, 95 % CI: −2.50 to −0.98) compared to untreated Class II patients. FFA treatment resulted in significant dentoalveolar and soft tissue changes. Several patient- or appliance-related factors seem to affect the treatment outcome. Long-term effectiveness of FFAs could not be assessed due to limited evidence. Conclusions: According to existing evidence, FFAs seem to be effective in improving Class II malocclusion in the short term, although their effects seem to be mainly dentoalveolar rather than skeletal. PMID:25995359

The effectiveness of lifestyle triple P in the Netherlands: a randomized controlled trial.

PubMed

Gerards, Sanne M P L; Dagnelie, Pieter C; Gubbels, Jessica S; van Buuren, Stef; Hamers, Femke J M; Jansen, Maria W J; van der Goot, Odilia H M; de Vries, Nanne K; Sanders, Matthew R; Kremers, Stef P J

2015-01-01

Lifestyle Triple P is a general parenting intervention which focuses on preventing further excessive weight gain in overweight and obese children. The objective of the current study was to assess the effectiveness of the Lifestyle Triple P intervention in the Netherlands. We used a parallel randomized controlled design to test the effectiveness of the intervention. In total, 86 child-parent triads (children 4-8 years old, overweight or obese) were recruited and randomly assigned (allocation ratio 1:1) to the Lifestyle Triple P intervention or the control condition. Parents in the intervention condition received a 14-week intervention consisting of ten 90-minute group sessions and four individual telephone sessions. Primary outcome measure was the children's body composition (BMI z-scores, waist circumference and skinfolds). The research assistant who performed the measurements was blinded for group assignment. Secondary outcome measures were the children's dietary behavior and physical activity level, parenting practices, parental feeding style, parenting style, and parental self-efficacy. Outcome measures were assessed at baseline and 4 months (short-term) and 12 months (long-term) after baseline. Multilevel multiple regression analyses were conducted to determine the effect of the intervention on primary and secondary outcome measures. No intervention effects were found on children's body composition. Analyses of secondary outcomes showed positive short-term intervention effects on children's soft-drink consumption and parental responsibility regarding physical activity, encouragement to eat, psychological control, and efficacy and satisfaction with parenting. Longer-term intervention effects were found on parent's report of children's time spent on sedentary behavior and playing outside, parental monitoring food intake, and responsibility regarding nutrition. Although the Lifestyle Triple P intervention showed positive effects on some parent reported child behaviors and parenting measures, no effects were visible on children's body composition or objectively measured physical activity. Several adjustments of the intervention content are recommended, for example including a booster session. Nederlands Trial Register NTR 2555.

META-ANALYSIS OF ACUTE EXERCISE EFFECTS ON STATE ANXIETY: AN UPDATE OF RANDOMIZED CONTROLLED TRIALS OVER THE PAST 25 YEARS.

PubMed

Ensari, Ipek; Greenlee, Tina A; Motl, Robert W; Petruzzello, Steven J

2015-08-01

One prominent and well-cited meta-analysis published nearly 25 years ago reported that an acute or single bout of exercise reduced state anxiety by approximately ¼ standard deviation. We conducted a meta-analysis of randomized controlled trials (RCTs) published after that meta-analysis for updating our understanding of the acute effects of exercise on state anxiety. We searched PubMed, EBSCOHost, Medline, PsycINFO, ERIC, and ScienceDirect for RCTs of acute exercise and state anxiety as an outcome. There were 36 RCTs that met inclusion criteria and yielded data for effect size (ES) generation (Cohen's d). An overall ES was calculated using a random effects model and expressed as Hedge's g. The weighted mean ES was small (Hedge's g = 0.16, standard error (SE) = 0.06), but statistically significant (P < 0.05), and indicated that a single bout of exercise resulted in an improvement in state anxiety compared with control. The overall ES was heterogeneous and post hoc, exploratory analyses using both random- and fixed-effects models identified several variables as moderators including sample age, sex and health status, baseline activity levels, exercise intensity, modality and control condition, randomization, overall study quality, and the anxiety measure (P < 0.05). The cumulative evidence from high quality studies indicates that acute bouts of exercise can yield a small reduction in state anxiety. The research is still plagued by floor effects associated with recruiting persons with normal or lower levels of state anxiety, and this should be overcome in subsequent trials. © 2015 Wiley Periodicals, Inc.

Cost-Effectiveness of Group and Internet Cognitive Behavioral Therapy for Insomnia in Adolescents: Results from a Randomized Controlled Trial

PubMed Central

De Bruin, Eduard J.; van Steensel, Francisca J.A.; Meijer, Anne Marie

2016-01-01

Study Objectives: To investigate cost-effectiveness of adolescent cognitive behavioral therapy for insomnia (CBTI) in group- and Internet-delivered formats, from a societal perspective with a time horizon of 1 y Methods: Costs and effects data up to 1-y follow-up were obtained from a randomized controlled trial (RCT) comparing Internet CBTI to face-to-face group CBTI. The study was conducted at the laboratory of the Research Institute of Child Development and Education at the University of Amsterdam, and the academic youth mental health care center UvAMinds in Amsterdam. Sixty-two participants meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for insomnia were randomized to face-to-face group CBTI (GT; n = 31, age = 15.6 y ± 1.8, 71.0% girls) or individual Internet CBTI (IT; n = 31, age = 15.4 y ± 1.5, 83.9% girls). The intervention consisted of six weekly sessions and a 2-mo follow up booster-session of CBTI, consisting of psychoeducation, sleep hygiene, restriction of time in bed, stimulus control, cognitive therapy, and relaxation techniques. GT sessions were held in groups of six to eight adolescents guided by two trained sleep therapists. IT consisted of individual Internet therapy with preprogrammed content similar to GT, and guided by trained sleep therapists. Results: Outcome measures were subjective sleep efficiency (SE) ≥ 85%, and quality-adjusted life-years (QALY). Analyses were conducted from a societal perspective. Incremental cost-effectiveness ratios (ICERs) were calculated using bootstrap sampling, and presented in cost-effectiveness planes. Primary analysis showed costs over 1 y were higher for GT but effects were similar for IT and GT. Bootstrapped ICERs demonstrated there is a high probability of IT being cost-effective compared to GT. Secondary analyses confirmed robustness of results. Conclusions: Internet CBTI is a cost-effective treatment compared to group CBTI for adolescents, although effects were largely similar for both formats. Further studies in a clinical setting are warranted. Clinical Trial Registration: ID: ISRCTN33922163; trial name: Effectiveness of cognitive behavioral therapy for sleeplessness in adolescents; URL: http://www.isrctn.com/ISRCTN33922163 Citation: De Bruin EJ, van Steensel FJ, Meijer AM. Cost-effectiveness of group and internet cognitive behavioral therapy for insomnia in adolescents: results from a randomized controlled trial. SLEEP 2016;39(8):1571–1581. PMID:27306272

Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses.

PubMed

Khankari, Nikhil K; Shu, Xiao-Ou; Wen, Wanqing; Kraft, Peter; Lindström, Sara; Peters, Ulrike; Schildkraut, Joellen; Schumacher, Fredrick; Bofetta, Paolo; Risch, Angela; Bickeböller, Heike; Amos, Christopher I; Easton, Douglas; Eeles, Rosalind A; Gruber, Stephen B; Haiman, Christopher A; Hunter, David J; Chanock, Stephen J; Pierce, Brandon L; Zheng, Wei

2016-09-01

Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using height-associated genetic variants identified in a genome-wide association study (GWAS), to evaluate the association of adult height with these cancers. A systematic review of prospective studies was conducted using the PubMed, Embase, and Web of Science databases. Using meta-analyses, results obtained from 62 studies were summarized for the association of a 10-cm increase in height with cancer risk. Mendelian randomization analyses were conducted using summary statistics obtained for 423 genetic variants identified from a recent GWAS of adult height and from a cancer genetics consortium study of multiple cancers that included 47,800 cases and 81,353 controls. For a 10-cm increase in height, the summary relative risks derived from the meta-analyses of prospective studies were 1.12 (95% CI 1.10, 1.15), 1.07 (95% CI 1.05, 1.10), and 1.06 (95% CI 1.02, 1.11) for colorectal, prostate, and lung cancers, respectively. Mendelian randomization analyses showed increased risks of colorectal (odds ratio [OR] = 1.58, 95% CI 1.14, 2.18) and lung cancer (OR = 1.10, 95% CI 1.00, 1.22) associated with each 10-cm increase in genetically predicted height. No association was observed for prostate cancer (OR = 1.03, 95% CI 0.92, 1.15). Our meta-analysis was limited to published studies. The sample size for the Mendelian randomization analysis of colorectal cancer was relatively small, thus affecting the precision of the point estimate. Our study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the risk of these cancers.

Effect of intradermal human recombinant copper-zinc superoxide dismutase on random pattern flaps in rats.

PubMed

Schein, Ophir; Westreich, Melvyn; Shalom, Avshalom

2013-09-01

Studies have focused on enhancing flap viability using superoxide dismutase (SOD), but only a few used SOD from human origin, and most gave the compound systemically. We evaluated the ability of SOD to improve random skin flap survival using human recombinant copper-zinc superoxide dismutase (Hr-CuZnSOD) in variable doses, injected intradermally into the flap. Seventy male Sprague Dawley rats were randomly assigned into 4 groups. Cephalic random pattern flaps were elevated on their backs and intradermal injections of different dosages of Hr-CuZnSOD were given 15 minutes before surgery. Flap survival was evaluated by fluorescein fluorescence. Analysis of variance (ANOVA) and t test statistical analyses were performed. Flap survival in all treated groups was significantly better than in the controls. The beneficial effect of HR-CuZnSOD on flap survival is attained when it is given intradermally into the flap tissue. Theoretically, Hr-CuZnSOD delivered with local anesthetics used in flap elevation may be a valuable clinical tool. Copyright © 2012 Wiley Periodicals, Inc.

Multilevel covariance regression with correlated random effects in the mean and variance structure.

PubMed

Quintero, Adrian; Lesaffre, Emmanuel

2017-09-01

Multivariate regression methods generally assume a constant covariance matrix for the observations. In case a heteroscedastic model is needed, the parametric and nonparametric covariance regression approaches can be restrictive in the literature. We propose a multilevel regression model for the mean and covariance structure, including random intercepts in both components and allowing for correlation between them. The implied conditional covariance function can be different across clusters as a result of the random effect in the variance structure. In addition, allowing for correlation between the random intercepts in the mean and covariance makes the model convenient for skewedly distributed responses. Furthermore, it permits us to analyse directly the relation between the mean response level and the variability in each cluster. Parameter estimation is carried out via Gibbs sampling. We compare the performance of our model to other covariance modelling approaches in a simulation study. Finally, the proposed model is applied to the RN4CAST dataset to identify the variables that impact burnout of nurses in Belgium. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Benefits and risks for primary prevention with statins in the elderly].

PubMed

Joseph, Jean-Philippe; Afonso, Mélanie; Berdaï, Driss; Salles, Nathalie; Bénard, Antoine; Gay, Bernard; Bonnet, Fabrice

2015-12-01

Statins in primary prevention before 75 years old reduce cardiovascular events from 20 to 30% and mortality from 10% with acceptable side effects. We investigated whether these results persisted for patients aged 75 and older taking statin. Methodic review of large randomized clinical trials and meta-analyzes that included patients 75 years and older treated with statins in primary prevention. Since the 1990s, a score of randomized controlled trials studying statins versus placebo in primary prevention were published and studied in meta-analyses. Exclusion criteria, including persons older than 70 years, are often restrictive. The impact on all-cause mortality in the four main studies and meta-analyses in over 75 years has not been demonstrated. On the other hand, a recent meta-analyses of observational studies including subjects between 70 and 89 years treated with statins found that low total cholesterol was associated with a moderate decrease in cardiovascular mortality, with no decrease in all-cause mortality. Moreover, in a common context of comorbidities in this age group, statins may be responsible for many adverse effects, drug interactions and impaired quality of life. Given the lack of formal evidence of effectiveness in terms of all-cause mortality and a high level of adverse effects, the benefit/risk of primary prevention with statins is not established in the elderly. The economic weight of statin prescriptions and their possible impact on quality of life justify an economic analysis of discontinuing statin therapy for people 75 years and older. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Patient Expectancy as a Mediator of Placebo Effects in Antidepressant Clinical Trials.

PubMed

Rutherford, Bret R; Wall, Melanie M; Brown, Patrick J; Choo, Tse-Hwei; Wager, Tor D; Peterson, Bradley S; Chung, Sarah; Kirsch, Irving; Roose, Steven P

2017-02-01

Causes of placebo effects in antidepressant trials have been inferred from observational studies and meta-analyses, but their mechanisms have not been directly established. The goal of this study was to examine in a prospective, randomized controlled trial whether patient expectancy mediates placebo effects in antidepressant studies. Adult outpatients with major depressive disorder were randomly assigned to open or placebo-controlled citalopram treatment. Following measurement of pre- and postrandomization expectancy, participants were treated with citalopram or placebo for 8 weeks. Independent samples t tests determined whether patient expectancy differed between the open and placebo-controlled groups, and mixed-effects models assessed group effects on Hamilton Depression Rating Scale (HAM-D) scores over time while controlling for treatment assignment. Finally, mediation analyses tested whether between-group differences in patient expectancy mediated the group effect on HAM-D scores. Postrandomization expectancy scores were significantly higher in the open group (mean=12.1 [SD=2.1]) compared with the placebo-controlled group (mean=11.0 [SD=2.0]). Mixed-effects modeling revealed a significant week-by-group interaction, indicating that HAM-D scores for citalopram-treated participants declined at a faster rate in the open group compared with the placebo-controlled group. Patient expectations postrandomization partially mediated group effects on week 8 HAM-D. Patient expectancy is a significant mediator of placebo effects in antidepressant trials. Expectancy-related interventions should be investigated as a means of controlling placebo responses in antidepressant clinical trials and improving patient outcome in clinical treatment.

Effects of a web-based tailored multiple-lifestyle intervention for adults: a two-year randomized controlled trial comparing sequential and simultaneous delivery modes.

PubMed

Schulz, Daniela N; Kremers, Stef P J; Vandelanotte, Corneel; van Adrichem, Mathieu J G; Schneider, Francine; Candel, Math J J M; de Vries, Hein

2014-01-27

Web-based computer-tailored interventions for multiple health behaviors can have a significant public health impact. Yet, few randomized controlled trials have tested this assumption. The objective of this paper was to test the effects of a sequential and simultaneous Web-based tailored intervention on multiple lifestyle behaviors. A randomized controlled trial was conducted with 3 tailoring conditions (ie, sequential, simultaneous, and control conditions) in the Netherlands in 2009-2012. Follow-up measurements took place after 12 and 24 months. The intervention content was based on the I-Change model. In a health risk appraisal, all respondents (N=5055) received feedback on their lifestyle behaviors that indicated whether they complied with the Dutch guidelines for physical activity, vegetable consumption, fruit consumption, alcohol intake, and smoking. Participants in the sequential (n=1736) and simultaneous (n=1638) conditions received tailored motivational feedback to change unhealthy behaviors one at a time (sequential) or all at the same time (simultaneous). Mixed model analyses were performed as primary analyses; regression analyses were done as sensitivity analyses. An overall risk score was used as outcome measure, then effects on the 5 individual lifestyle behaviors were assessed and a process evaluation was performed regarding exposure to and appreciation of the intervention. Both tailoring strategies were associated with small self-reported behavioral changes. The sequential condition had the most significant effects compared to the control condition after 12 months (T1, effect size=0.28). After 24 months (T2), the simultaneous condition was most effective (effect size=0.18). All 5 individual lifestyle behaviors changed over time, but few effects differed significantly between the conditions. At both follow-ups, the sequential condition had significant changes in smoking abstinence compared to the simultaneous condition (T1 effect size=0.31; T2 effect size=0.41). The sequential condition was more effective in decreasing alcohol consumption than the control condition at 24 months (effect size=0.27). Change was predicted by the amount of exposure to the intervention (total visiting time: beta=-.06; P=.01; total number of visits: beta=-.11; P<.001). Both interventions were appreciated well by respondents without significant differences between conditions. Although evidence was found for the effectiveness of both programs, no simple conclusive finding could be drawn about which intervention mode was more effective. The best kind of intervention may depend on the behavior that is targeted or on personal preferences and motivation. Further research is needed to identify moderators of intervention effectiveness. The results need to be interpreted in view of the high and selective dropout rates, multiple comparisons, and modest effect sizes. However, a large number of people were reached at low cost and behavioral change was achieved after 2 years. Nederlands Trial Register: NTR 2168; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2168 (Archived by WebCite at http://www.webcitation.org/6MbUqttYB).

Does Mother Know Best? Treatment Adherence as a Function of Anticipated Treatment Benefit

PubMed Central

Glymour, M. Maria; Nguyen, Quynh; Matsouaka, Roland; Tchetgen Tchetgen, Eric J.; Schmidt, Nicole M.; Osypuk, Theresa L.

2016-01-01

Background We describe bias resulting from individualized treatment selection, which occurs when treatment has heterogeneous effects and individuals selectively choose treatments of greatest benefit to themselves. This pernicious bias may confound estimates from observational studies and lead to important misinterpretation of intent-to-treat analyses of randomized trials. Despite the potentially serious threat to inferences, individualized treatment selection has rarely been formally described or assessed. Methods The Moving to Opportunity (MTO) trial randomly assigned subsidized rental vouchers to low-income families in high-poverty public housing. We assessed the Kessler-6 psychological distress and Behavior Problems Index outcomes for 2,829 adolescents 4–7 years after randomization. Among families randomly assigned to receive vouchers, we estimated probability of moving (treatment), predicted by pre-randomization characteristics (c-statistic=0.63). We categorized families into tertiles of this estimated probability of moving, and compared instrumental variable effect estimates for moving on Behavior Problems Index and Kessler-6 across tertiles. Results Instrumental variable estimated effects of moving on behavioral problems index were most adverse for boys least likely to move (b=0.93; 95% CI: 0.33, 1.53) compared to boys most likely to move (b=0.14; 95% CI: −0.15, 0.44; p=.02 for treatment*tertile interaction). Effects on Kessler-6 were more beneficial for girls least likely to move compared to girls most likely to move (−0.62 vs. 0.02; interaction p=.03). Conclusions Evidence of Individualized treatment selection differed by child gender and outcome and should be evaluated in randomized trial reports, especially when heterogeneous treatment effects are likely and non-adherence is common. PMID:26628424

Specifying a target trial prevents immortal time bias and other self-inflicted injuries in observational analyses

PubMed Central

Hernán, Miguel A.; Sauer, Brian C.; Hernández-Díaz, Sonia; Platt, Robert; Shrier, Ian

2016-01-01

Many analyses of observational data are attempts to emulate a target trial. The emulation of the target trial may fail when researchers deviate from simple principles that guide the design and analysis of randomized experiments. We review a framework to describe and prevent biases, including immortal time bias, that result from a failure to align start of follow-up, specification of eligibility, and treatment assignment. We review some analytic approaches to avoid these problems in comparative effectiveness or safety research. PMID:27237061

Long-Chain Omega-3 Fatty Acids Eicosapentaenoic Acid and Docosahexaenoic Acid and Blood Pressure: A Meta-Analysis of Randomized Controlled Trials

PubMed Central

Van Elswyk, Mary; Alexander, Dominik D.

2014-01-01

BACKGROUND Although a large body of literature has been devoted to examining the relationship between eicosapentaenoic and docosahexaenoic acids (EPA+DHA) and blood pressure, past systematic reviews have been hampered by narrow inclusion criteria and a limited scope of analytical subgroups. In addition, no meta-analysis to date has captured the substantial volume of randomized controlled trials (RCTs) published in the past 2 years. The objective of this meta-analysis was to examine the effect of EPA+DHA, without upper dose limits and including food sources, on blood pressure in RCTs. METHODS Random-effects meta-analyses were used to generate weighted group mean differences and 95% confidence intervals (CIs) between the EPA+DHA group and the placebo group. Analyses were conducted for subgroups defined by key subject or study characteristics. RESULTS Seventy RCTs were included. Compared with placebo, EPA+DHA provision reduced systolic blood pressure (−1.52mm Hg; 95% confidence interval (CI) = −2.25 to −0.79) and diastolic blood pressure (−0.99mm Hg; 95% CI = −1.54 to −0.44) in the meta-analyses of all studies combined. The strongest effects of EPA+DHA were observed among untreated hypertensive subjects (systolic blood pressure = −4.51mm Hg, 95% CI = −6.12 to −2.83; diastolic blood pressure = −3.05mm Hg, 95% CI = −4.35 to −1.74), although blood pressure also was lowered among normotensive subjects (systolic blood pressure = −1.25mm Hg, 95% CI = −2.05 to −0.46; diastolic blood pressure = −0.62mm Hg, 95% CI = −1.22 to −0.02). CONCLUSIONS Overall, available evidence from RCTs indicates that provision of EPA+DHA reduces systolic blood pressure, while provision of ≥2 grams reduces diastolic blood pressure. PMID:24610882

Long-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and blood pressure: a meta-analysis of randomized controlled trials.

PubMed

Miller, Paige E; Van Elswyk, Mary; Alexander, Dominik D

2014-07-01

Although a large body of literature has been devoted to examining the relationship between eicosapentaenoic and docosahexaenoic acids (EPA+DHA) and blood pressure, past systematic reviews have been hampered by narrow inclusion criteria and a limited scope of analytical subgroups. In addition, no meta-analysis to date has captured the substantial volume of randomized controlled trials (RCTs) published in the past 2 years. The objective of this meta-analysis was to examine the effect of EPA+DHA, without upper dose limits and including food sources, on blood pressure in RCTs. Random-effects meta-analyses were used to generate weighted group mean differences and 95% confidence intervals (CIs) between the EPA+DHA group and the placebo group. Analyses were conducted for subgroups defined by key subject or study characteristics. Seventy RCTs were included. Compared with placebo, EPA+DHA provision reduced systolic blood pressure (-1.52 mm Hg; 95% confidence interval (CI) = -2.25 to -0.79) and diastolic blood pressure (-0.99 mm Hg; 95% CI = -1.54 to -0.44) in the meta-analyses of all studies combined. The strongest effects of EPA+DHA were observed among untreated hypertensive subjects (systolic blood pressure = -4.51 mm Hg, 95% CI = -6.12 to -2.83; diastolic blood pressure = -3.05 mm Hg, 95% CI = -4.35 to - 1.74), although blood pressure also was lowered among normotensive subjects (systolic blood pressure = -1.25 mm Hg, 95% CI = -2.05 to -0.46; diastolic blood pressure = -0.62 mm Hg, 95% CI = -1.22 to -0.02). Overall, available evidence from RCTs indicates that provision of EPA+DHA reduces systolic blood pressure, while provision of ≥2 grams reduces diastolic blood pressure. © The Author 2014. Published by Oxford University Press on behalf of the American Journal of Hypertension.

Internet and computer-based cognitive behavioral therapy for anxiety and depression in youth: a meta-analysis of randomized controlled outcome trials.

PubMed

Ebert, David Daniel; Zarski, Anna-Carlotta; Christensen, Helen; Stikkelbroek, Yvonne; Cuijpers, Pim; Berking, Matthias; Riper, Heleen

2015-01-01

Anxiety and depression in children and adolescents are undertreated. Computer- and Internet-based cognitive behavioral treatments (cCBT) may be an attractive treatment alternative to regular face-to-face treatment.This meta-analysis aims to evaluate whether cCBT is effective for treating symptoms of anxiety and depression in youth. We conducted systematic searches in bibliographical databases (Pubmed, Cochrane controlled trial register, PsychInfo) up to December 4, 2013. Only randomized controlled trials in which a computer-, Internet- or mobile-based cognitive behavioral intervention targeting either depression, anxiety or both in children or adolescents up to the age of 25 were compared to a control condition were selected. We employed a random-effects pooling model in overall effect analyses and a mixed effect model for sub-group analyses. Searches resulted in identifying 13 randomized trials, including 796 children and adolescents that met inclusion criteria. Seven studies were directed at treating anxiety, four studies at depression, and two were of a transdiagnostic nature, targeting both anxiety and depression. The overall mean effect size (Hedges' g) of cCBT on symptoms of anxiety or depression at post-test was g=0.72 (95% CI:0.55-0.90, numbers needed to be treated (NNT)=2.56). Heterogeneity was low (I²=20.14%, 95% CI: 0-58%). The superiority of cCBT over controls was evident for interventions targeting anxiety (g=0.68; 95% CI: 0.45-0.92; p < .001; NNT=2.70) and for interventions targeting depression (g=0.76; 95% CI: 0.41-0.12; p < .001; NNT=2.44) as well as for transdiagnostic interventions (g=0.94; 95% CI: 0.23-2.66; p < .001; NNT=2.60). Results provide evidence for the efficacy of cCBT in the treatment of anxiety and depressive symptoms in youth. Hence, such interventions may be a promising treatment alternative when evidence based face-to-face treatment is not feasible. Future studies should examine long-term effects of treatments and should focus on obtaining patient-level data from existing studies, to perform an individual patient data meta-analysis.

Effects of the X:IT smoking intervention: a school-based cluster randomized trial.

PubMed

Andersen, Anette; Krølner, Rikker; Bast, Lotus Sofie; Thygesen, Lau Caspar; Due, Pernille

2015-12-01

Uptake of smoking in adolescence is still of major public health concern. Evaluations of school-based programmes for smoking prevention show mixed results. The aim of this study was to examine the effect of X:IT, a multi-component school-based programme to prevent adolescent smoking. Data from a Danish cluster randomized trial included 4041 year-7 students (mean age: 12.5) from 51 intervention and 43 control schools. Outcome measure 'current smoking' was dichotomized into smoking daily, weekly, monthly or more seldom vs do not smoke. Analyses were adjusted for baseline covariates: sex, family socioeconomic position (SEP), best friend's smoking and parental smoking. We performed multilevel, logistic regression analyses of available cases and intention-to-treat (ITT) analyses, replacing missing outcome values by multiple imputation. At baseline, 4.7% and 6.8% of the students at the intervention and the control schools smoked, respectively. After 1 year of the intervention, the prevalence was 7.9% and 10.7%, respectively. At follow-up, 553 students (13.7%) did not answer the question on smoking. Available case analyses: crude odds ratios (OR) for smoking at intervention schools compared with control schools: 0.65 (0.48-0.88) and adjusted: 0.70 (0.47-1.04). ITT analyses: crude OR for smoking at intervention schools compared with control schools: 0.67 (0.50-0.89) and adjusted: 0.61 (0.45-0.82). Students at intervention schools had a lower risk of smoking after a year of intervention in year 7. This multi-component intervention involving educational, parental and context-related intervention components seems to be efficient in lowering or postponing smoking uptake in Danish adolescents. © The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Early studies reported extreme findings with large variability: a meta-epidemiologic study in the field of endocrinology.

PubMed

Wang, Zhen; Alahdab, Fares; Almasri, Jehad; Haydour, Qusay; Mohammed, Khaled; Abu Dabrh, Abd Moain; Prokop, Larry J; Alfarkh, Wedad; Lakis, Sumaya; Montori, Victor M; Murad, Mohammad Hassan

2016-04-01

To evaluate the presence of extreme findings and fluctuation in effect size in endocrinology. We systematically identified all meta-analyses published in 2014 in the field of endocrinology. Within each meta-analysis, the effect size of the primary binary outcome was compared across studies according to their order of publication. We pooled studies using the DerSimonian and Laird random-effects method. Heterogeneity was evaluated using the I(2) and tau(2). Twelve percent of the included 100 meta-analyses reported the largest effect size in the very first published study. The largest effect size occurred in the first 2 earliest studies in 31% of meta-analyses. When the effect size was the largest in the first published study, it was three times larger than the final pooled effect (ratio of rates, 3.26; 95% confidence interval: 1.80, 5.90). The largest heterogeneity measured by I(2) was observed in 18% of the included meta-analyses when combining the first 2 studies or 17% when combing the first 3 studies. In endocrinology, early studies reported extreme findings with large variability. This behavior of the evidence needs to be taken into account when used to formulate clinical policies. Copyright © 2016 Elsevier Inc. All rights reserved.

Transfusion Indication Threshold Reduction (TITRe2) randomized controlled trial in cardiac surgery: statistical analysis plan.

PubMed

Pike, Katie; Nash, Rachel L; Murphy, Gavin J; Reeves, Barnaby C; Rogers, Chris A

2015-02-22

The Transfusion Indication Threshold Reduction (TITRe2) trial is the largest randomized controlled trial to date to compare red blood cell transfusion strategies following cardiac surgery. This update presents the statistical analysis plan, detailing how the study will be analyzed and presented. The statistical analysis plan has been written following recommendations from the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, prior to database lock and the final analysis of trial data. Outlined analyses are in line with the Consolidated Standards of Reporting Trials (CONSORT). The study aims to randomize 2000 patients from 17 UK centres. Patients are randomized to either a restrictive (transfuse if haemoglobin concentration <7.5 g/dl) or liberal (transfuse if haemoglobin concentration <9 g/dl) transfusion strategy. The primary outcome is a binary composite outcome of any serious infectious or ischaemic event in the first 3 months following randomization. The statistical analysis plan details how non-adherence with the intervention, withdrawals from the study, and the study population will be derived and dealt with in the analysis. The planned analyses of the trial primary and secondary outcome measures are described in detail, including approaches taken to deal with multiple testing, model assumptions not being met and missing data. Details of planned subgroup and sensitivity analyses and pre-specified ancillary analyses are given, along with potential issues that have been identified with such analyses and possible approaches to overcome such issues. ISRCTN70923932 .

Pilot Study of Treatment for Major Depression Among Women Prisoners with Substance Use Disorder

PubMed Central

Johnson, Jennifer E.; Zlotnick, Caron

2012-01-01

This study, the largest randomized controlled trial of treatment for major depressive disorder (MDD) in an incarcerated population to date, wave-randomized 38 incarcerated women (6 waves) in prison substance use treatment with MDD to group interpersonal psychotherapy (IPT) or to an attention-matched control. Intent-to-treat analyses found that IPT participants had significantly lower depressive symptoms at the end of 8 weeks of in-prison treatment than did control participants. Control participants improved later, after prison release. IPT's rapid effect on MDD within prison may reduce serious in-prison consequences of MDD. PMID:22694906

Telephone-based continuing care counseling in substance abuse treatment: economic analysis of a randomized trial

PubMed Central

Daley, Marilyn C.; Neuman, Matthew J.; Blaakman, Aaron P.; McKay, James R.

2016-01-01

Purpose To investigate whether telephone-based continuing care (TEL) is a promising alternative to traditional face-to-face counseling for clients in treatment for substance abuse. Methods Patients with alcohol and/or cocaine dependence who had completed a 4-week intensive outpatient program were randomly assigned through urn randomization into one of three 12-week interventions: standard continuing care (STD), in-person relapse prevention (RP), or telephone-based continuing care (TEL). This study performed cost, cost-effectiveness, and cost-benefit analyses of TEL and RP compared to STD, using results from the randomized clinical trial with two years of follow up (359 participants). In addition, the study examined the potential moderating effect of baseline patient costs on economic outcomes. Results The study found that TEL was less expensive per client from the societal perspective ($569) than STD ($870) or RP ($1,684). TEL also was also significantly more effective, with an abstinence rate of 57.1% compared to 46.7% for STD (p<0.05). Thus TEL dominated STD, with a highly favorable negative incremental cost-effectiveness ratio (−$1,400 per abstinent year). TEL also proved favorable under a benefit-cost perspective. Conclusions TEL proved to be a cost-effective and cost-beneficial contributor to long-term recovery over two years. Because TEL dominated STD care interventions, wider adoption should be considered. PMID:26718395

Telephone-based continuing care counseling in substance abuse treatment: Economic analysis of a randomized trial.

PubMed

Shepard, Donald S; Daley, Marilyn C; Neuman, Matthew J; Blaakman, Aaron P; McKay, James R

2016-02-01

To investigate whether telephone-based continuing care (TEL) is a promising alternative to traditional face-to-face counseling for clients in treatment for substance abuse. Patients with alcohol and/or cocaine dependence who had completed a 4-week intensive outpatient program were randomly assigned through urn randomization into one of three 12-week interventions: standard continuing care (STD), in-person relapse prevention (RP), or telephone-based continuing care (TEL). This study performed cost, cost-effectiveness, and cost-benefit analyses of TEL and RP compared to STD, using results from the randomized clinical trial with two years of follow up (359 participants). In addition, the study examined the potential moderating effect of baseline patient costs on economic outcomes. The study found that TEL was less expensive per client from the societal perspective ($569) than STD ($870) or RP ($1684). TEL also was also significantly more effective, with an abstinence rate of 57.1% compared to 46.7% for STD (p<0.05). Thus TEL dominated STD, with a highly favorable negative incremental cost-effectiveness ratio (-$1400 per abstinent year). TEL also proved favorable under a benefit-cost perspective. TEL proved to be a cost-effective and cost-beneficial contributor to long-term recovery over two years. Because TEL dominated STD care interventions, wider adoption should be considered. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effectiveness and cost-effectiveness of a health coaching intervention to improve the lifestyle of patients with knee osteoarthritis: cluster randomized clinical trial.

PubMed

Carmona-Terés, Victoria; Lumillo-Gutiérrez, Iris; Jodar-Fernández, Lina; Rodriguez-Blanco, Teresa; Moix-Queraltó, Joanna; Pujol-Ribera, Enriqueta; Mas, Xavier; Batlle-Gualda, Enrique; Gobbo-Montoya, Milena; Berenguera, Anna

2015-02-25

The prevalence of osteoarthritis and knee osteoarthritis in the Spanish population is estimated at 17% and 10.2%, respectively. The clinical guidelines concur that the first line treatment for knee osteoarthritis should be non-pharmacological and include weight loss, physical activity and self-management of pain. Health Coaching has been defined as an intervention that facilitates the achievement of health improvement goals, the reduction of unhealthy lifestyles, the improvement of self-management for chronic conditions and quality of life enhancement. The aim of this study is to analyze the effectiveness, cost-effectiveness and cost-utility of a health coaching intervention on quality of life, pain, overweight and physical activity in patients from 18 primary care centres of Barcelona with knee osteoarthritis. Methodology from the Medical Research Council on developing complex interventions. Phase 1: Intervention modelling and operationalization through a qualitative, socioconstructivist study using theoretical sampling with 10 in-depth interviews to patients with knee osteoarthritis and 4 discussion groups of 8-12 primary care professionals, evaluated using a sociological discourse analysis. Phase 2: Effectiveness, cost-effectiveness and cost-utility study with a community-based randomized clinical trial. 360 patients with knee osteoarthritis (180 in each group). Randomization unit: Primary Care Centre. Intervention Group: will receive standard care plus 20-hour health coaching and follow-up sessions. will receive standard care. quality of life as measured by the WOMAC index. Data Analyses: will include standardized response mean and multilevel analysis of repeated measures. Economic analysis: based on cost-effectiveness and cost-utility measures. Phase 3: Evaluation of the intervention programme with a qualitative study. Methodology as in Phase 1. If the analyses show the cost-effectiveness and cost-utility of the intervention the results can be incorporated into the clinical guidelines for the management of knee osteoarthritis in primary care. ISRCTN57405925. Registred 20 June 2014.

Clinical and psychological moderators of the effect of mindfulness-based cognitive therapy on persistent pain in women treated for primary breast cancer - explorative analyses from a randomized controlled trial.

PubMed

Johannsen, M; O'Toole, M S; O'Connor, M; Jensen, A B; Zachariae, R

2017-02-01

Mindfulness-based intervention has been found efficacious in reducing persistent pain in women treated for breast cancer. Little, however, is known about possible moderators of the effect. We explored clinical and psychological moderators of the effect on pain intensity previously found in a randomized controlled trial of mindfulness-based cognitive therapy (MBCT) with women treated for breast cancer with persistent pain. A total of 129 women treated for breast cancer reporting persistent pain were randomized to MBCT or a wait-list control. The primary outcome of pain intensity (11-point numeric rating scale) was measured at baseline, post-intervention, three, and six months follow-up. Proposed clinical moderators included age, axillary lymph node dissection (ALND), radiotherapy, and endocrine treatment. Psychological moderators included psychological distress [the Hospital Anxiety and Depression Scale (HADS)], the adult attachment dimensions anxiety and avoidance [the Experiences in Close Relationships Short Form (the ECR-SF)], and alexithymia [the Toronto Alexithymia Scale (TAS-20)]. Multi-level models were used to test moderation effects over time, i.e. time × group × moderator. Only attachment avoidance (p = 0.03, d = 0.36) emerged as a statistically significant moderator. Higher levels of attachment avoidance predicted a larger effect of MBCT in reducing pain intensity compared with lower levels attachment avoidance. None of the remaining psychological or clinical moderators reached statistical significance. However, based on the effect size, radiotherapy (p = 0.075, d = 0.49) was indicated as a possible clinical moderator of the effect, with radiotherapy being associated with a smaller effect of MBCT on pain intensity over time compared with no radiotherapy. Attachment avoidance, and potentially radiotherapy, may be clinically relevant factors for identifying the patients who may benefit most from MBCT as a pain intervention. Due to the exploratory nature of the analyses, the results should be considered preliminary.

Logistic random effects regression models: a comparison of statistical packages for binary and ordinal outcomes.

PubMed

Li, Baoyue; Lingsma, Hester F; Steyerberg, Ewout W; Lesaffre, Emmanuel

2011-05-23

Logistic random effects models are a popular tool to analyze multilevel also called hierarchical data with a binary or ordinal outcome. Here, we aim to compare different statistical software implementations of these models. We used individual patient data from 8509 patients in 231 centers with moderate and severe Traumatic Brain Injury (TBI) enrolled in eight Randomized Controlled Trials (RCTs) and three observational studies. We fitted logistic random effects regression models with the 5-point Glasgow Outcome Scale (GOS) as outcome, both dichotomized as well as ordinal, with center and/or trial as random effects, and as covariates age, motor score, pupil reactivity or trial. We then compared the implementations of frequentist and Bayesian methods to estimate the fixed and random effects. Frequentist approaches included R (lme4), Stata (GLLAMM), SAS (GLIMMIX and NLMIXED), MLwiN ([R]IGLS) and MIXOR, Bayesian approaches included WinBUGS, MLwiN (MCMC), R package MCMCglmm and SAS experimental procedure MCMC.Three data sets (the full data set and two sub-datasets) were analysed using basically two logistic random effects models with either one random effect for the center or two random effects for center and trial. For the ordinal outcome in the full data set also a proportional odds model with a random center effect was fitted. The packages gave similar parameter estimates for both the fixed and random effects and for the binary (and ordinal) models for the main study and when based on a relatively large number of level-1 (patient level) data compared to the number of level-2 (hospital level) data. However, when based on relatively sparse data set, i.e. when the numbers of level-1 and level-2 data units were about the same, the frequentist and Bayesian approaches showed somewhat different results. The software implementations differ considerably in flexibility, computation time, and usability. There are also differences in the availability of additional tools for model evaluation, such as diagnostic plots. The experimental SAS (version 9.2) procedure MCMC appeared to be inefficient. On relatively large data sets, the different software implementations of logistic random effects regression models produced similar results. Thus, for a large data set there seems to be no explicit preference (of course if there is no preference from a philosophical point of view) for either a frequentist or Bayesian approach (if based on vague priors). The choice for a particular implementation may largely depend on the desired flexibility, and the usability of the package. For small data sets the random effects variances are difficult to estimate. In the frequentist approaches the MLE of this variance was often estimated zero with a standard error that is either zero or could not be determined, while for Bayesian methods the estimates could depend on the chosen "non-informative" prior of the variance parameter. The starting value for the variance parameter may be also critical for the convergence of the Markov chain.

Contingency Management interventions for non-prescribed drug use during treatment for opiate addiction: A systematic review and meta-analysis.

PubMed

Ainscough, Tom S; McNeill, Ann; Strang, John; Calder, Robert; Brose, Leonie S

2017-09-01

Use of non-prescribed drugs during treatment for opiate addiction reduces treatment success, creating a need for effective interventions. This review aimed to assess the efficacy of contingency management, a behavioural treatment that uses rewards to encourage desired behaviours, for treating non-prescribed drug use during opiate addiction treatment. A systematic search of the databases Embase, PsychInfo, PsychArticles and Medline from inception to March 2015 was performed. Random effects meta-analysis tested the use of contingency management to treat the use of drugs during opiate addiction treatment, using either longest duration of abstinence (LDA) or percentage of negative samples (PNS). Random effects moderator analyses were performed for six potential moderators: drug targeted for intervention, decade in which the study was carried out, study quality, intervention duration, type of reinforcer, and form of opiate treatment. The search returned 3860 papers; 22 studies met inclusion criteria and were meta-analysed. Follow-up data was only available for three studies, so all analyses used end of treatment data. Contingency management performed significantly better than control in reducing drug use measured using LDA (d=0.57, 95% CI: 0.42-0.72) or PNS (d=0.41) (95% CI: 0.28-0.54). This was true for all drugs other than opiates. The only significant moderator was drug targeted (LDA: Q=10.75, p=0.03). Contingency management appears to be efficacious for treating most drug use during treatment for opiate addiction. Further research is required to ascertain the full effects of moderating variables, and longer term effects. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

On the repeated measures designs and sample sizes for randomized controlled trials.

PubMed

Tango, Toshiro

2016-04-01

For the analysis of longitudinal or repeated measures data, generalized linear mixed-effects models provide a flexible and powerful tool to deal with heterogeneity among subject response profiles. However, the typical statistical design adopted in usual randomized controlled trials is an analysis of covariance type analysis using a pre-defined pair of "pre-post" data, in which pre-(baseline) data are used as a covariate for adjustment together with other covariates. Then, the major design issue is to calculate the sample size or the number of subjects allocated to each treatment group. In this paper, we propose a new repeated measures design and sample size calculations combined with generalized linear mixed-effects models that depend not only on the number of subjects but on the number of repeated measures before and after randomization per subject used for the analysis. The main advantages of the proposed design combined with the generalized linear mixed-effects models are (1) it can easily handle missing data by applying the likelihood-based ignorable analyses under the missing at random assumption and (2) it may lead to a reduction in sample size, compared with the simple pre-post design. The proposed designs and the sample size calculations are illustrated with real data arising from randomized controlled trials. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Permissive or Trophic Enteral Nutrition and Full Enteral Nutrition Had Similar Effects on Clinical Outcomes in Intensive Care: A Systematic Review of Randomized Clinical Trials.

PubMed

Silva, Camila F A; de Vasconcelos, Simone G; da Silva, Thales A; Silva, Flávia M

2018-01-26

The aim of this study was to systematically review the effect of permissive underfeeding/trophic feeding on the clinical outcomes of critically ill patients. A systematic review of randomized clinical trials to evaluate the mortality, length of stay, and mechanical ventilation duration in patients randomized to either hypocaloric or full-energy enteral nutrition was performed. Data sources included PubMed and Scopus and the reference lists of the articles retrieved. Two independent reviewers participated in all phases of this systematic review as proposed by the Cochrane Handbook, and the review was reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 7 randomized clinical trials that included a total of 1,717 patients were reviewed. Intensive care unit length of stay and mechanical ventilation duration were not statistically different between the intervention and control groups in all randomized clinical trials, and mortality rate was also not different between the groups. In conclusion, hypocaloric enteral nutrition had no significantly different effects on morbidity and mortality in critically ill patients when compared with full-energy nutrition. It is still necessary to determine the safety of this intervention in this group of patients, the optimal amount of energy provided, and the duration of this therapy. © 2018 American Society for Parenteral and Enteral Nutrition.

Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes: Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study

PubMed Central

Chin, Melanie P.; Bakris, George L.; Block, Geoffrey A.; Chertow, Glenn M.; Goldsberry, Angie; Inker, Lesley A.; Heerspink, Hiddo J.L.; O'Grady, Megan; Pergola, Pablo E.; Wanner, Christoph; Warnock, David G.; Meyer, Colin J.

2018-01-01

Background Increases in measured inulin clearance, measured creatinine clearance, and estimated glomerular filtration rate (eGFR) have been observed with bardoxolone methyl in 7 studies enrolling approximately 2,600 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The largest of these studies was Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), a multinational, randomized, double-blind, placebo-controlled phase 3 trial which enrolled patients with T2D and CKD stage 4. The BEACON trial was terminated after preliminary analyses showed that patients randomized to bardoxolone methyl experienced significantly higher rates of heart failure events. We performed post-hoc analyses to characterize changes in kidney function induced by bardoxolone methyl. Methods Patients in ­BEACON (n = 2,185) were randomized 1: 1 to receive once-daily bardoxolone methyl (20 mg) or placebo. We compared the effects of bardoxolone methyl and placebo on a post-hoc composite renal endpoint consisting of ≥30% decline from baseline in eGFR, eGFR <15 mL/min/1.73 m2, and end-stage renal disease (ESRD) events (provision of dialysis or kidney transplantation). Results Consistent with prior studies, patients randomized to bardoxolone methyl experienced mean increases in eGFR that were sustained through study week 48. Moreover, increases in eGFR from baseline were sustained 4 weeks after cessation of treatment. Patients randomized to bardoxolone methyl were significantly less likely to experience the composite renal endpoint (hazards ratio 0.48 [95% CI 0.36–0.64]; p < 0.0001). Conclusions Bardoxolone methyl preserves kidney function and may delay the onset of ESRD in patients with T2D and stage 4 CKD. PMID:29402767

Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes: Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study.

PubMed

Chin, Melanie P; Bakris, George L; Block, Geoffrey A; Chertow, Glenn M; Goldsberry, Angie; Inker, Lesley A; Heerspink, Hiddo J L; O'Grady, Megan; Pergola, Pablo E; Wanner, Christoph; Warnock, David G; Meyer, Colin J

2018-01-01

Increases in measured inulin clearance, measured creatinine clearance, and estimated glomerular filtration rate (eGFR) have been observed with bardoxolone methyl in 7 studies enrolling approximately 2,600 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The largest of these studies was Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), a multinational, randomized, double-blind, placebo-controlled phase 3 trial which enrolled patients with T2D and CKD stage 4. The BEACON trial was terminated after preliminary analyses showed that patients randomized to bardoxolone methyl experienced significantly higher rates of heart failure events. We performed post-hoc analyses to characterize changes in kidney function induced by bardoxolone methyl. Patients in -BEACON (n = 2,185) were randomized 1: 1 to receive once-daily bardoxolone methyl (20 mg) or placebo. We compared the effects of bardoxolone methyl and placebo on a post-hoc composite renal endpoint consisting of ≥30% decline from baseline in eGFR, eGFR <15 mL/min/1.73 m2, and end-stage renal disease (ESRD) events (provision of dialysis or kidney transplantation). Consistent with prior studies, patients randomized to bardoxolone methyl experienced mean increases in eGFR that were sustained through study week 48. Moreover, increases in eGFR from baseline were sustained 4 weeks after cessation of treatment. Patients randomized to bardoxolone methyl were significantly less likely to experience the composite renal endpoint (hazards ratio 0.48 [95% CI 0.36-0.64]; p < 0.0001). Bardoxolone methyl preserves kidney function and may delay the onset of ESRD in patients with T2D and stage 4 CKD. © 2018 The Author(s) Published by S. Karger AG, Basel.

Effects of a Web-Based Computer-Tailored Game to Reduce Binge Drinking Among Dutch Adolescents: A Cluster Randomized Controlled Trial

PubMed Central

Crutzen, Rik; Mercken, Liesbeth; Candel, Math; de Vries, Hein

2016-01-01

Background Binge drinking among Dutch adolescents is among the highest in Europe. Few interventions so far have focused on adolescents aged 15 to 19 years. Because binge drinking increases significantly during those years, it is important to develop binge drinking prevention programs for this group. Web-based computer-tailored interventions can be an effective tool for reducing this behavior in adolescents. Embedding the computer-tailored intervention in a serious game may make it more attractive to adolescents. Objective The aim was to assess whether a Web-based computer-tailored intervention is effective in reducing binge drinking in Dutch adolescents aged 15 to 19 years. Secondary outcomes were reduction in excessive drinking and overall consumption during the previous week. Personal characteristics associated with program adherence were also investigated. Methods A cluster randomized controlled trial was conducted among 34 Dutch schools. Each school was randomized into either an experimental (n=1622) or a control (n=1027) condition. Baseline assessment took place in January and February 2014. At baseline, demographic variables and alcohol use were assessed. Follow-up assessment of alcohol use took place 4 months later (May and June 2014). After the baseline assessment, participants in the experimental condition started with the intervention consisting of a game about alcohol in which computer-tailored feedback regarding motivational characteristics was embedded. Participants in the control condition only received the baseline questionnaire. Both groups received the 4-month follow-up questionnaire. Effects of the intervention were assessed using logistic regression mixed models analyses for binge and excessive drinking and linear regression mixed models analyses for weekly consumption. Factors associated with intervention adherence in the experimental condition were explored by means of a linear regression model. Results In total, 2649 adolescents participated in the baseline assessment. At follow-up, 824 (31.11%) adolescents returned. The intervention was effective in reducing binge drinking among adolescents aged 15 years (P=.03) and those aged 16 years when they participated in at least 2 intervention sessions (P=.04). Interaction effects between excessive drinking and educational level (P=.08) and between weekly consumption and age (P=.09) were found; however, in-depth analyses revealed no significant subgroup effects for both interaction effects. Additional analyses revealed that prolonged use of the intervention was associated with stronger effects for binge drinking. Yet, overall adherence to the intervention was low. Analyses revealed that being Protestant, female, younger, a nonbinge drinker, and having a higher educational background were associated with adherence. Conclusions The intervention was effective for adolescents aged 15 and 16 years concerning binge drinking. Prevention messages may be more effective for those at the start of their drinking career, whereas other methods may be needed for those with a longer history of alcohol consumption. Despite using game elements, intervention completion was low. Trial Registration Dutch Trial Register: NTR4048; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4048 (Archived by WebCite® at http://www.webcitation.org/6eSJD3FiY) PMID:26842694

Effects of a Web-Based Computer-Tailored Game to Reduce Binge Drinking Among Dutch Adolescents: A Cluster Randomized Controlled Trial.

PubMed

Jander, Astrid; Crutzen, Rik; Mercken, Liesbeth; Candel, Math; de Vries, Hein

2016-02-03

Binge drinking among Dutch adolescents is among the highest in Europe. Few interventions so far have focused on adolescents aged 15 to 19 years. Because binge drinking increases significantly during those years, it is important to develop binge drinking prevention programs for this group. Web-based computer-tailored interventions can be an effective tool for reducing this behavior in adolescents. Embedding the computer-tailored intervention in a serious game may make it more attractive to adolescents. The aim was to assess whether a Web-based computer-tailored intervention is effective in reducing binge drinking in Dutch adolescents aged 15 to 19 years. Secondary outcomes were reduction in excessive drinking and overall consumption during the previous week. Personal characteristics associated with program adherence were also investigated. A cluster randomized controlled trial was conducted among 34 Dutch schools. Each school was randomized into either an experimental (n=1622) or a control (n=1027) condition. Baseline assessment took place in January and February 2014. At baseline, demographic variables and alcohol use were assessed. Follow-up assessment of alcohol use took place 4 months later (May and June 2014). After the baseline assessment, participants in the experimental condition started with the intervention consisting of a game about alcohol in which computer-tailored feedback regarding motivational characteristics was embedded. Participants in the control condition only received the baseline questionnaire. Both groups received the 4-month follow-up questionnaire. Effects of the intervention were assessed using logistic regression mixed models analyses for binge and excessive drinking and linear regression mixed models analyses for weekly consumption. Factors associated with intervention adherence in the experimental condition were explored by means of a linear regression model. In total, 2649 adolescents participated in the baseline assessment. At follow-up, 824 (31.11%) adolescents returned. The intervention was effective in reducing binge drinking among adolescents aged 15 years (P=.03) and those aged 16 years when they participated in at least 2 intervention sessions (P=.04). Interaction effects between excessive drinking and educational level (P=.08) and between weekly consumption and age (P=.09) were found; however, in-depth analyses revealed no significant subgroup effects for both interaction effects. Additional analyses revealed that prolonged use of the intervention was associated with stronger effects for binge drinking. Yet, overall adherence to the intervention was low. Analyses revealed that being Protestant, female, younger, a nonbinge drinker, and having a higher educational background were associated with adherence. The intervention was effective for adolescents aged 15 and 16 years concerning binge drinking. Prevention messages may be more effective for those at the start of their drinking career, whereas other methods may be needed for those with a longer history of alcohol consumption. Despite using game elements, intervention completion was low. Dutch Trial Register: NTR4048; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4048 (Archived by WebCite® at http://www.webcitation.org/6eSJD3FiY).

Effects of Recombinant Human Growth Hormone for Osteoporosis: Systematic Review and Meta-Analysis.

PubMed

Atkinson, Hayden F; Moyer, Rebecca F; Yacoub, Daniel; Coughlin, Dexter; Birmingham, Trevor B

2017-03-01

Our objective was to evaluate the efficacy of recombinant human growth hormone (GH) on bone mineral density (BMD) in persons age 50 and older, with normal pituitary function, with or at risk for developing osteoporosis. We systematically reviewed randomized clinical trials (RCTs), searching six databases, and conducted meta-analyses to examine GH effects on BMD of the lumbar spine and femoral neck. Data for fracture incidence, bone metabolism biomarkers, and adverse events were also extracted and analysed. Thirteen RCTs met the eligibility criteria. Pooled effect sizes suggested no significant GH effect on BMD. Pooled effect sizes were largest, but nonsignificant, when compared to placebo. GH had a significant effect on several bone metabolism biomarkers. A significantly higher rate of adverse events was observed in the GH groups. Meta-analysis of RCTs suggests that GH treatment for persons with or at risk for developing osteoporosis results in very small, nonsignificant increases in BMD.

Habitual coffee consumption and cognitive function: a Mendelian randomization meta-analysis in up to 415,530 participants.

PubMed

Zhou, Ang; Taylor, Amy E; Karhunen, Ville; Zhan, Yiqiang; Rovio, Suvi P; Lahti, Jari; Sjögren, Per; Byberg, Liisa; Lyall, Donald M; Auvinen, Juha; Lehtimäki, Terho; Kähönen, Mika; Hutri-Kähönen, Nina; Perälä, Mia Maria; Michaëlsson, Karl; Mahajan, Anubha; Lind, Lars; Power, Chris; Eriksson, Johan G; Raitakari, Olli T; Hägg, Sara; Pedersen, Nancy L; Veijola, Juha; Järvelin, Marjo-Riitta; Munafò, Marcus R; Ingelsson, Erik; Llewellyn, David J; Hyppönen, Elina

2018-05-14

Coffee's long-term effect on cognitive function remains unclear with studies suggesting both benefits and adverse effects. We used Mendelian randomization to investigate the causal relationship between habitual coffee consumption and cognitive function in mid- to later life. This included up to 415,530 participants and 300,760 coffee drinkers from 10 meta-analysed European ancestry cohorts. In each cohort, composite cognitive scores that capture global cognition and memory were computed using available tests. A genetic score derived using CYP1A1/2 (rs2472297) and AHR (rs6968865) was chosen as a proxy for habitual coffee consumption. Null associations were observed when examining the associations of the genetic score with global and memory cognition (β = -0.0007, 95% C.I. -0.009 to 0.008, P = 0.87; β = -0.001, 95% C.I. -0.005 to 0.002, P = 0.51, respectively), with high consistency between studies (P heterogeneity  > 0.4 for both). Domain specific analyses using available cognitive measures in the UK Biobank also did not support effects by habitual coffee intake for reaction time, pairs matching, reasoning or prospective memory (P ≥ 0.05 for all). Despite the power to detect very small effects, our meta-analysis provided no evidence for causal long-term effects of habitual coffee consumption on global cognition or memory.

Assessing the effectiveness and cost-effectiveness of audit and feedback on physician’s prescribing indicators: study protocol of a randomized controlled trial with economic evaluation

PubMed Central

2012-01-01

Background Physician prescribing is the most frequent medical intervention with a highest impact on healthcare costs and outcomes. Therefore improving and promoting rational drug use is a great interest. We aimed to assess the effectiveness and cost-effectiveness of two forms of conducting prescribing audit and feedback interventions and a printed educational material intervention in improving physician prescribing. Method/design A four-arm randomized trial with economic evaluation will be conducted in Tehran. Three interventions (routine feedback, revised feedback, and printed educational material) and a no intervention control arm will be compared. Physicians working in outpatient practices are randomly allocated to one of the four arms using stratified randomized sampling. The interventions are developed based on a review of literature, physician interviews, current experiences in Iran and with theoretical insights from the Theory of Planned Behavior. Effects of the interventions on improving antibiotics and corticosteroids prescribing will be assessed in regression analyses. Cost data will be assessed from a health care provider’s perspective and incremental cost-effectiveness ratios will be calculated. Discussion This study will determine the effectiveness and cost-effectiveness of three interventions and allow us to determine the most effective interventions in improving prescribing pattern. If the interventions are cost-effective, they will likely be applied nationwide. Trial registration Iranian Registry of Clinical Trials Registration Number: IRCT201106086740N1Pharmaceutical Sciences Research Center of TUMS Ethics Committee Registration Number: 90-02-27-07 PMID:23351564

Survival in Malnourished Older Patients Receiving Post-Discharge Nutritional Support; Long-Term Results of a Randomized Controlled Trial.

PubMed

Neelemaat, F; van Keeken, S; Langius, J A E; de van der Schueren, M A E; Thijs, A; Bosmans, J E

2017-01-01

Previous analyses have shown that a post-discharge individualized nutritional intervention had positive effects on body weight, lean body mass, functional limitations and fall incidents in malnourished older patients. However, the impact of this intervention on survival has not yet been studied. The objective of this randomized controlled study was to examine the effect of a post-discharge individualized nutritional intervention on survival in malnourished older patients. Malnourished older patients, aged ≥ 60 years, were randomized during hospitalization to a three-months post-discharge nutritional intervention group (protein and energy enriched diet, oral nutritional supplements, vitamin D3/calcium supplement and telephone counseling by a dietitian) or to a usual care regimen (control group). Survival data were collected 4 years after enrollment. Survival analyses were performed using intention-to-treat analysis by Log-rank tests and Cox regression adjusted for confounders. The study population consisted of 94 men (45%) and 116 women with a mean age of 74.5 (SD 9.5) years. There were no statistically significant differences in baseline characteristics. Survival data was available in 208 out of 210 patients. After 1 and 4 years of follow-up, survival rates were respectively 66% and 29% in the intervention group (n=104) and 73% and 30% in the control group (n=104). There were no statistically significant differences in survival between the two groups 1 year (HR= 0.933, 95% CI=0.675-1.289) and 4 years after enrollment (HR=0.928, 95% CI=0.671-1.283). The current study failed to show an effect of a three-months post-discharge multi-component nutritional intervention in malnourished older patients on long-term survival, despite the positive effects on short-term outcome such as functional limitations and falls.

Confidence intervals for the between-study variance in random-effects meta-analysis using generalised heterogeneity statistics: should we use unequal tails?

PubMed

Jackson, Dan; Bowden, Jack

2016-09-07

Confidence intervals for the between study variance are useful in random-effects meta-analyses because they quantify the uncertainty in the corresponding point estimates. Methods for calculating these confidence intervals have been developed that are based on inverting hypothesis tests using generalised heterogeneity statistics. Whilst, under the random effects model, these new methods furnish confidence intervals with the correct coverage, the resulting intervals are usually very wide, making them uninformative. We discuss a simple strategy for obtaining 95 % confidence intervals for the between-study variance with a markedly reduced width, whilst retaining the nominal coverage probability. Specifically, we consider the possibility of using methods based on generalised heterogeneity statistics with unequal tail probabilities, where the tail probability used to compute the upper bound is greater than 2.5 %. This idea is assessed using four real examples and a variety of simulation studies. Supporting analytical results are also obtained. Our results provide evidence that using unequal tail probabilities can result in shorter 95 % confidence intervals for the between-study variance. We also show some further results for a real example that illustrates how shorter confidence intervals for the between-study variance can be useful when performing sensitivity analyses for the average effect, which is usually the parameter of primary interest. We conclude that using unequal tail probabilities when computing 95 % confidence intervals for the between-study variance, when using methods based on generalised heterogeneity statistics, can result in shorter confidence intervals. We suggest that those who find the case for using unequal tail probabilities convincing should use the '1-4 % split', where greater tail probability is allocated to the upper confidence bound. The 'width-optimal' interval that we present deserves further investigation.

Treatment effects of Ginkgo biloba extract EGb 761® on the spectrum of behavioral and psychological symptoms of dementia: meta-analysis of randomized controlled trials.

PubMed

Savaskan, Egemen; Mueller, Heiko; Hoerr, Robert; von Gunten, Armin; Gauthier, Serge

2018-03-01

ABSTRACTBackground:In randomized controlled trials, Ginkgo biloba extract EGb 761® has been found to be effective in the treatment of behavioral and psychological symptoms of dementia (BPSD). To assess the effects of EGb 761® on specific BPSD, we analyzed data from all randomized, placebo-controlled, at least 20-week, trials of EGb 761® enrolling patients with dementia (probable Alzheimer's disease (AD), probable vascular dementia or probable AD with cerebrovascular disease) who had clinically significant BPSD (Neuropsychiatric Inventory (NPI) total score at least 6). Data were pooled and joint analyses of NPI single item composite and caregiver distress scores were performed by meta-analysis with a fixed effects model. Four trials involving 1628 patients (EGb 761®, 814; placebo, 814) were identified; treatment duration was 22 or 24 weeks; the daily dose of EGb 761® was 240 mg in all trials. Pooled analyses including data from the full analysis sets of all trials (EGb 761®, 796 patients; placebo, 802 patients) revealed significant superiority of EGb 761® over placebo in total scores and 10 single symptom scores. Regarding caregiver distress scores, EGb 761®-treated patients improved significantly more than those receiving placebo in all symptoms except delusions, hallucinations, and elation/euphoria. The benefit of EGb 761® mainly consists of improvement in symptoms present at baseline, but the incidence of some symptoms was also decreased. Twenty two- to twenty four-week treatment with Ginkgo biloba extract EGb 761® improved BPSD (except psychotic-like features) and caregiver distress caused by such symptoms.

Cost-Effectiveness of an Internet-Delivered Treatment for Substance Abuse: Data from a Multisite Randomized Controlled Trial

PubMed Central

Murphy, Sean M.; Campbell, Aimee N. C.; Ghitza, Udi E.; Kyle, Tiffany L.; Bailey, Genie L.; Nunes, Edward V.; Polsky, Daniel

2016-01-01

Background Substance misuse and excessive alcohol consumption are major public health issues. Internet-based interventions for substance use disorders (SUDs) are a relatively new method for addressing barriers to access and supplementing existing care. This study examines cost-effectiveness in a multisite, randomized trial of an internet-based version of the community reinforcement approach (CRA) with contingency management (CM) known as the Therapeutic Education System (TES). Methods Economic evaluation of the 12-week trial with follow-up at 24 and 36 weeks. 507 individuals who were seeking therapy for alcohol or other substance use disorders at 10 outpatient community-based treatment programs were recruited and randomized to either treatment as usual (TAU) or TES+TAU. Sub-analyses were completed on participants with a poorer prognosis (i.e., those not abstinent at study entry). Results From the provider’s perspective, TES+TAU as it was implemented in this study costs $278 (SE=87) more than TAU alone after 12 weeks. The quality-adjusted life years gained by TES+TAU and TAU were similar; however, TES+TAU has at least a 95% chance of being considered cost-effective for providers and payers with willingness-to-pay thresholds as low as $20,000 per abstinent year. Findings for the subgroup not abstinent at study entry are slightly more favorable. Conclusions With regard to the clinical outcome of abstinence, our cost-effectiveness findings of TES+TAU compare favorably to those found elsewhere in the CM literature. The analyses performed here serve as an initial economic framework for future studies integrating technology into SUD therapy. Clinical trial registration NCT01104805. PMID:26880594

Results from the Periodontitis and Vascular Events (PAVE) Study: a pilot multicentered, randomized, controlled trial to study effects of periodontal therapy in a secondary prevention model of cardiovascular disease.

PubMed

Offenbacher, Steven; Beck, James D; Moss, Kevin; Mendoza, Luisito; Paquette, David W; Barrow, David A; Couper, David J; Stewart, Dawn D; Falkner, Karen L; Graham, Susan P; Grossi, Sara; Gunsolley, John C; Madden, Theresa; Maupome, Gerardo; Trevisan, Maurizio; Van Dyke, Thomas E; Genco, Robert J

2009-02-01

In the Periodontitis and Vascular Events (PAVE) pilot study, periodontal therapy was provided as an intervention in a secondary cardiac event prevention model through five coordinated cardiac-dental centers. Subjects were randomized to either community care or protocol provided scaling and root planing to evaluate effects on periodontal status and systemic levels of high-sensitivity C-reactive protein (hs-CRP). After 6 months, there was a significant reduction in mean probing depth and extent of 4- or 5-mm pockets. However, there were no significant differences in attachment levels, bleeding upon probing, or extent of subgingival calculus comparing subjects assigned to protocol therapy (n = 151) to those assigned to community care (n = 152). Using intent-to-treat analyses, there was no significant effect on serum hs-CRP levels at 6 months. However, 48% of the subjects randomized to community care received preventive or periodontal treatments. Secondary analyses demonstrated that consideration of any preventive or periodontal care (i.e., any treatment) compared to no treatment showed a significant reduction in the percentage of people with elevated hs-CRP (values >3 mg/l) at 6 months. However, obesity nullified the periodontal treatment effects on hs-CRP reduction. The adjusted odds ratio for hs-CRP levels >3 mg/l at 6 months for any treatment versus no treatment among non-obese individuals was 0.26 (95% confidence interval: 0.09 to 0.72), adjusting for smoking, marital status, and gender. This pilot study demonstrated the critical role of considering obesity as well as rigorous preventive and periodontal care in trials designed to reduce cardiovascular risk.

Results From the Periodontitis and Vascular Events (PAVE) Study: A Pilot Multicentered, Randomized, Controlled Trial to Study Effects of Periodontal Therapy in a Secondary Prevention Model of Cardiovascular Disease

PubMed Central

Offenbacher, Steven; Beck, James D.; Moss, Kevin; Mendoza, Luisito; Paquette, David W.; Barrow, David A.; Couper, David J.; Stewart, Dawn D.; Falkner, Karen L.; Graham, Susan P.; Grossi, Sara; Gunsolley, John C.; Madden, Theresa; Maupome, Gerardo; Trevisan, Maurizio; Van Dyke, Thomas E.; Genco, Robert J.

2009-01-01

Background In the Periodontitis and Vascular Events (PAVE) pilot study, periodontal therapy was provided as an intervention in a secondary cardiac event prevention model through five coordinated cardiac– dental centers. Methods Subjects were randomized to either community care or protocol provided scaling and root planing to evaluate effects on periodontal status and systemic levels of high-sensitivity C-reactive protein (hs-CRP). Results After 6 months, there was a significant reduction in mean probing depth and extent of 4- or 5-mm pockets. However, there were no significant differences in attachment levels, bleeding upon probing, or extent of subgingival calculus comparing subjects assigned to protocol therapy (n = 151) to those assigned to community care (n = 152). Using intent-to-treat analyses, there was no significant effect on serum hs-CRP levels at 6 months. However, 48% of the subjects randomized to community care received preventive or periodontal treatments. Secondary analyses demonstrated that consideration of any preventive or periodontal care (i.e., any treatment) compared to no treatment showed a significant reduction in the percentage of people with elevated hs-CRP (values >3 mg/l) at 6 months. However, obesity nullified the periodontal treatment effects on hs-CRP reduction. The adjusted odds ratio for hs-CRP levels >3 mg/l at 6 months for any treatment versus no treatment among non-obese individuals was 0.26 (95%confidence interval: 0.09 to 0.72), adjusting for smoking, marital status, and gender. Conclusion This pilot study demonstrated the critical role of considering obesity as well as rigorous preventive and periodontal care in trials designed to reduce cardiovascular risk. PMID:19186958

Cost-effectiveness of an internet-delivered treatment for substance abuse: Data from a multisite randomized controlled trial.

PubMed

Murphy, Sean M; Campbell, Aimee N C; Ghitza, Udi E; Kyle, Tiffany L; Bailey, Genie L; Nunes, Edward V; Polsky, Daniel

2016-04-01

Substance misuse and excessive alcohol consumption are major public health issues. Internet-based interventions for substance use disorders (SUDs) are a relatively new method for addressing barriers to access and supplementing existing care. This study examines cost-effectiveness in a multisite, randomized trial of an internet-based version of the community reinforcement approach (CRA) with contingency management (CM) known as the Therapeutic Education System (TES). Economic evaluation of the 12-week trial with follow-up at 24 and 36 weeks. 507 individuals who were seeking therapy for alcohol or other substance use disorders at 10 outpatient community-based treatment programs were recruited and randomized to either treatment as usual (TAU) or TES+TAU. Sub-analyses were completed on participants with a poorer prognosis (i.e., those not abstinent at study entry). From the provider's perspective, TES+TAU as it was implemented in this study costs $278 (SE=87) more than TAU alone after 12 weeks. The quality-adjusted life years gained by TES+TAU and TAU were similar; however, TES+TAU has at least a 95% chance of being considered cost-effective for providers and payers with willingness-to-pay thresholds as low as $20,000 per abstinent year. Findings for the subgroup not abstinent at study entry are slightly more favorable. With regard to the clinical outcome of abstinence, our cost-effectiveness findings of TES+TAU compare favorably to those found elsewhere in the CM literature. The analyses performed here serve as an initial economic framework for future studies integrating technology into SUD therapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

POWER for reproductive health: results from a social marketing campaign promoting female and male condoms.

PubMed

Bull, Sheana S; Posner, Samuel F; Ortiz, Charlene; Beaty, Brenda; Benton, Kathryn; Lin, Lillian; Pals, Sherri L; Evans, Tom

2008-07-01

To evaluate effects of a 6-month social marketing campaign on awareness of, attitudes toward and use of female as well as male condoms for 15-25 year-old-women. Using a time-space sampling methodology, we conducted a cross-sectional survey of 3407 women at pre-campaign in 12 western U.S. neighborhoods on female and male condom awareness, attitudes, and use. Six of the 12 study neighborhoods were randomly selected to receive the POWER social marketing campaign designed to impact condom knowledge, attitudes, and use. The campaign was followed with another cross-sectional survey of 3,003 women in all 12 study neighborhoods on condom knowledge, attitudes, use and awareness of POWER materials. We compared pre-and post-campaign surveys to determine the efficacy of POWER and conducted post hoc analyses on post-campaign data to determine if exposure to POWER was related to higher levels of positive condom attitudes and norms and condom use. We found no differences between neighborhoods with and without the POWER campaign with regard to our primary outcomes. To diagnose reasons for this null effect, we examined outcomes post hoc examining the influence of POWER exposure. Post hoc analyses show some evidence that exposure to POWER was associated with condom use. In the context of the nested trial, this raises concerns that post test only evaluations are limited. Establishing the efficacy of a social marketing campaign is challenging. This group randomized trial showed a null effect. Social marketing campaigns may need to have more media channels and saturation before they can show behavioral effects. Using a nested design with randomization at the community level and probability sampling introduces rigor not commonly seen in evaluations of social marketing campaigns.

Genetic analysis of body weights of individually fed beef bulls in South Africa using random regression models.

PubMed

Selapa, N W; Nephawe, K A; Maiwashe, A; Norris, D

2012-02-08

The aim of this study was to estimate genetic parameters for body weights of individually fed beef bulls measured at centralized testing stations in South Africa using random regression models. Weekly body weights of Bonsmara bulls (N = 2919) tested between 1999 and 2003 were available for the analyses. The model included a fixed regression of the body weights on fourth-order orthogonal Legendre polynomials of the actual days on test (7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77, and 84) for starting age and contemporary group effects. Random regressions on fourth-order orthogonal Legendre polynomials of the actual days on test were included for additive genetic effects and additional uncorrelated random effects of the weaning-herd-year and the permanent environment of the animal. Residual effects were assumed to be independently distributed with heterogeneous variance for each test day. Variance ratios for additive genetic, permanent environment and weaning-herd-year for weekly body weights at different test days ranged from 0.26 to 0.29, 0.37 to 0.44 and 0.26 to 0.34, respectively. The weaning-herd-year was found to have a significant effect on the variation of body weights of bulls despite a 28-day adjustment period. Genetic correlations amongst body weights at different test days were high, ranging from 0.89 to 1.00. Heritability estimates were comparable to literature using multivariate models. Therefore, random regression model could be applied in the genetic evaluation of body weight of individually fed beef bulls in South Africa.

Effects of relationship education on couple communication and satisfaction: A randomized controlled trial with low-income couples.

PubMed

Williamson, Hannah C; Altman, Noemi; Hsueh, JoAnn; Bradbury, Thomas N

2016-02-01

Although preventive educational interventions for couples have been examined in more than 100 experimental studies, the value of this work is limited by reliance on economically advantaged populations and by an absence of data on proposed mediators and moderators. Data from the Supporting Healthy Marriage Project-a randomized, controlled trial of relationship education for couples living with low incomes-were therefore analyzed to test whether intervention effects on relationship satisfaction would be mediated by observational assessments of relationship communication and whether any such effects would be moderated by couples' pretreatment risk. Within the larger sample of Supporting Healthy Marriage Project couples randomized to a relationship education or no-treatment control condition, the present analyses focus on the 1,034 couples who provided (a) data on sociodemographic risk at baseline, (b) observational data on couple communication 12 months after randomization, and (c) reports of relationship satisfaction 30 months after randomization. Intervention couples reported higher satisfaction at 30 months than control couples, regardless of their level of pretreatment risk. Among higher risk couples, the intervention improved observed communication as well. Contrary to prediction, treatment effects on satisfaction were not mediated by improvements in communication, and improvements in communication did not translate into greater satisfaction. Relationship education programs produce small improvements in relationship satisfaction and communication, particularly for couples at elevated sociodemographic risk. The absence of behavioral effects on satisfaction indicates, however, that the mechanisms by which couples may benefit from relationship education are not yet well understood. (c) 2016 APA, all rights reserved).

The Effects of Aerobic and Anaerobic Training Programs Applied to Elite Wrestlers on Body Mass Index (BMI) and Blood Lipids

ERIC Educational Resources Information Center

Demirel, Nurcan; Özbay, Serhat; Kaya, Fatih

2018-01-01

The purpose of this study is to analyse the effects of aerobic and anaerobic training programs applied to elite wrestlers on body mass index (BMI) and blood lipids. 20 elite wrestlers, whose average age is (experimental group; 15.20 ± 4.61, n = 10), control group; 15.90 ± 2.08, n = 10), participated in the study and they were randomly divided into…

Branched-chain amino acids for people with hepatic encephalopathy.

PubMed

Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo; Córdoba, Juan; Marchesini, Giulio; Borre, Mette; Aagaard, Niels Kristian; Vilstrup, Hendrik

2015-02-25

Hepatic encephalopathy is a brain dysfunction with neurological and psychiatric changes associated with liver insufficiency or portal-systemic shunting. The severity ranges from minor symptoms to coma. A Cochrane systematic review including 11 randomised clinical trials on branched-chain amino acids (BCAA) versus control interventions has evaluated if BCAA may benefit people with hepatic encephalopathy. To evaluate the beneficial and harmful effects of BCAA versus any control intervention for people with hepatic encephalopathy. We identified trials through manual and electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index on 2 October 2014. We included randomised clinical trials, irrespective of the bias control, language, or publication status. The authors independently extracted data based on published reports and collected data from the primary investigators. We changed our primary outcomes in this update of the review to include mortality (all cause), hepatic encephalopathy (number of people without improved manifestations of hepatic encephalopathy), and adverse events. The analyses included random-effects and fixed-effect meta-analyses. We performed subgroup, sensitivity, regression, and trial sequential analyses to evaluate sources of heterogeneity (including intervention, and participant and trial characteristics), bias (using The Cochrane Hepato-Biliary Group method), small-study effects, and the robustness of the results after adjusting for sparse data and multiplicity. We graded the quality of the evidence using the GRADE approach. We found 16 randomised clinical trials including 827 participants with hepatic encephalopathy classed as overt (12 trials) or minimal (four trials). Eight trials assessed oral BCAA supplements and seven trials assessed intravenous BCAA. The control groups received placebo/no intervention (two trials), diets (10 trials), lactulose (two trials), or neomycin (two trials). In 15 trials, all participants had cirrhosis. Based on the combined Cochrane Hepato-Biliary Group score, we classed seven trials as low risk of bias and nine trials as high risk of bias (mainly due to lack of blinding or for-profit funding). In a random-effects meta-analysis of mortality, we found no difference between BCAA and controls (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.69 to 1.11; 760 participants; 15 trials; moderate quality of evidence). We found no evidence of small-study effects. Sensitivity analyses of trials with a low risk of bias found no beneficial or detrimental effect of BCAA on mortality. Trial sequential analysis showed that the required information size was not reached, suggesting that additional evidence was needed. BCAA had a beneficial effect on hepatic encephalopathy (RR 0.73, 95% CI 0.61 to 0.88; 827 participants; 16 trials; high quality of evidence). We found no small-study effects and confirmed the beneficial effect of BCAA in a sensitivity analysis that only included trials with a low risk of bias (RR 0.71, 95% CI 0.52 to 0.96). The trial sequential analysis showed that firm evidence was reached. In a fixed-effect meta-analysis, we found that BCAA increased the risk of nausea and vomiting (RR 5.56; 2.93 to 10.55; moderate quality of evidence). We found no beneficial or detrimental effects of BCAA on nausea or vomiting in a random-effects meta-analysis or on quality of life or nutritional parameters. We did not identify predictors of the intervention effect in the subgroup, sensitivity, or meta-regression analyses. In sensitivity analyses that excluded trials with a lactulose or neomycin control, BCAA had a beneficial effect on hepatic encephalopathy (RR 0.76, 95% CI 0.63 to 0.92). Additional sensitivity analyses found no difference between BCAA and lactulose or neomycin (RR 0.66, 95% CI 0.34 to 1.30). In this updated review, we included five additional trials. The analyses showed that BCAA had a beneficial effect on hepatic encephalopathy. We found no effect on mortality, quality of life, or nutritional parameters, but we need additional trials to evaluate these outcomes. Likewise, we need additional randomised clinical trials to determine the effect of BCAA compared with interventions such as non-absorbable disaccharides, rifaximin, or other antibiotics.

Branched-chain amino acids for people with hepatic encephalopathy.

PubMed

Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo; Marchesini, Giulio; Borre, Mette; Aagaard, Niels Kristian; Vilstrup, Hendrik

2017-05-18

Hepatic encephalopathy is a brain dysfunction with neurological and psychiatric changes associated with liver insufficiency or portal-systemic shunting. The severity ranges from minor symptoms to coma. A Cochrane systematic review including 11 randomised clinical trials on branched-chain amino acids (BCAA) versus control interventions has evaluated if BCAA may benefit people with hepatic encephalopathy. To evaluate the beneficial and harmful effects of BCAA versus any control intervention for people with hepatic encephalopathy. We identified trials through manual and electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded and Conference Proceedings Citation Index - Science, and LILACS (May 2017). We included randomised clinical trials, irrespective of the bias control, language, or publication status. The authors independently extracted data based on published reports and collected data from the primary investigators. We changed our primary outcomes in this update of the review to include mortality (all cause), hepatic encephalopathy (number of people without improved manifestations of hepatic encephalopathy), and adverse events. The analyses included random-effects and fixed-effect meta-analyses. We performed subgroup, sensitivity, regression, and trial sequential analyses to evaluate sources of heterogeneity (including intervention, and participant and trial characteristics), bias (using The Cochrane Hepato-Biliary Group method), small-study effects, and the robustness of the results after adjusting for sparse data and multiplicity. We graded the quality of the evidence using the GRADE approach. We found 16 randomised clinical trials including 827 participants with hepatic encephalopathy classed as overt (12 trials) or minimal (four trials). Eight trials assessed oral BCAA supplements and seven trials assessed intravenous BCAA. The control groups received placebo/no intervention (two trials), diets (10 trials), lactulose (two trials), or neomycin (two trials). In 15 trials, all participants had cirrhosis. We classed seven trials as low risk of bias and nine trials as high risk of bias (mainly due to lack of blinding or for-profit funding). In a random-effects meta-analysis of mortality, we found no difference between BCAA and controls (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.69 to 1.11; 760 participants; 15 trials; moderate quality of evidence). We found no evidence of small-study effects. Sensitivity analyses of trials with a low risk of bias found no beneficial or detrimental effect of BCAA on mortality. Trial sequential analysis showed that the required information size was not reached, suggesting that additional evidence was needed. BCAA had a beneficial effect on hepatic encephalopathy (RR 0.73, 95% CI 0.61 to 0.88; 827 participants; 16 trials; high quality of evidence). We found no small-study effects and confirmed the beneficial effect of BCAA in a sensitivity analysis that only included trials with a low risk of bias (RR 0.71, 95% CI 0.52 to 0.96). The trial sequential analysis showed that firm evidence was reached. In a fixed-effect meta-analysis, we found that BCAA increased the risk of nausea and vomiting (RR 5.56; 2.93 to 10.55; moderate quality of evidence). We found no beneficial or detrimental effects of BCAA on nausea or vomiting in a random-effects meta-analysis or on quality of life or nutritional parameters. We did not identify predictors of the intervention effect in the subgroup, sensitivity, or meta-regression analyses. In sensitivity analyses that excluded trials with a lactulose or neomycin control, BCAA had a beneficial effect on hepatic encephalopathy (RR 0.76, 95% CI 0.63 to 0.92). Additional sensitivity analyses found no difference between BCAA and lactulose or neomycin (RR 0.66, 95% CI 0.34 to 1.30). In this updated review, we included five additional trials. The analyses showed that BCAA had a beneficial effect on hepatic encephalopathy. We found no effect on mortality, quality of life, or nutritional parameters, but we need additional trials to evaluate these outcomes. Likewise, we need additional randomised clinical trials to determine the effect of BCAA compared with interventions such as non-absorbable disaccharides, rifaximin, or other antibiotics.

Branched-chain amino acids for people with hepatic encephalopathy.

PubMed

Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo; Córdoba, Juan; Marchesini, Giulio; Borre, Mette; Aagaard, Niels Kristian; Vilstrup, Hendrik

2015-09-17

Hepatic encephalopathy is a brain dysfunction with neurological and psychiatric changes associated with liver insufficiency or portal-systemic shunting. The severity ranges from minor symptoms to coma. A Cochrane systematic review including 11 randomised clinical trials on branched-chain amino acids (BCAA) versus control interventions has evaluated if BCAA may benefit people with hepatic encephalopathy. To evaluate the beneficial and harmful effects of BCAA versus any control intervention for people with hepatic encephalopathy. We identified trials through manual and electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index (August 2015). We included randomised clinical trials, irrespective of the bias control, language, or publication status. The authors independently extracted data based on published reports and collected data from the primary investigators. We changed our primary outcomes in this update of the review to include mortality (all cause), hepatic encephalopathy (number of people without improved manifestations of hepatic encephalopathy), and adverse events. The analyses included random-effects and fixed-effect meta-analyses. We performed subgroup, sensitivity, regression, and trial sequential analyses to evaluate sources of heterogeneity (including intervention, and participant and trial characteristics), bias (using The Cochrane Hepato-Biliary Group method), small-study effects, and the robustness of the results after adjusting for sparse data and multiplicity. We graded the quality of the evidence using the GRADE approach. We found 16 randomised clinical trials including 827 participants with hepatic encephalopathy classed as overt (12 trials) or minimal (four trials). Eight trials assessed oral BCAA supplements and seven trials assessed intravenous BCAA. The control groups received placebo/no intervention (two trials), diets (10 trials), lactulose (two trials), or neomycin (two trials). In 15 trials, all participants had cirrhosis. We classed seven trials as low risk of bias and nine trials as high risk of bias (mainly due to lack of blinding or for-profit funding). In a random-effects meta-analysis of mortality, we found no difference between BCAA and controls (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.69 to 1.11; 760 participants; 15 trials; moderate quality of evidence). We found no evidence of small-study effects. Sensitivity analyses of trials with a low risk of bias found no beneficial or detrimental effect of BCAA on mortality. Trial sequential analysis showed that the required information size was not reached, suggesting that additional evidence was needed. BCAA had a beneficial effect on hepatic encephalopathy (RR 0.73, 95% CI 0.61 to 0.88; 827 participants; 16 trials; high quality of evidence). We found no small-study effects and confirmed the beneficial effect of BCAA in a sensitivity analysis that only included trials with a low risk of bias (RR 0.71, 95% CI 0.52 to 0.96). The trial sequential analysis showed that firm evidence was reached. In a fixed-effect meta-analysis, we found that BCAA increased the risk of nausea and vomiting (RR 5.56; 2.93 to 10.55; moderate quality of evidence). We found no beneficial or detrimental effects of BCAA on nausea or vomiting in a random-effects meta-analysis or on quality of life or nutritional parameters. We did not identify predictors of the intervention effect in the subgroup, sensitivity, or meta-regression analyses. In sensitivity analyses that excluded trials with a lactulose or neomycin control, BCAA had a beneficial effect on hepatic encephalopathy (RR 0.76, 95% CI 0.63 to 0.92). Additional sensitivity analyses found no difference between BCAA and lactulose or neomycin (RR 0.66, 95% CI 0.34 to 1.30). In this updated review, we included five additional trials. The analyses showed that BCAA had a beneficial effect on hepatic encephalopathy. We found no effect on mortality, quality of life, or nutritional parameters, but we need additional trials to evaluate these outcomes. Likewise, we need additional randomised clinical trials to determine the effect of BCAA compared with interventions such as non-absorbable disaccharides, rifaximin, or other antibiotics.

Sugars, obesity, and cardiovascular disease: results from recent randomized control trials.

PubMed

Rippe, James M; Angelopoulos, Theodore J

2016-11-01

The relationship between sugar consumption and various health-related sequelas is controversial. Some investigators have argued that excessive sugar consumption is associated with increased risk of obesity, coronary heart disease, diabetes (T2D), metabolic syndrome, non-alcoholic fatty liver disease, and stimulation of reward pathways in the brain potentially causing excessive caloric consumption. These concerns have influenced organizations such as the World Health Organization, the Scientific Advisory Committee on Nutrition in England not to exceed 5 % of total energy and the Dietary Guidelines for Americans Advisory Committee 2015 to recommend upper limits of sugar consumption not to exceed 10 % of calories. Data from many randomized control trials (RCTs) do not support linkages between sugar consumption at normal levels within the human diet and various adverse metabolic and health-related effects. Fructose and glucose are typically consumed together in roughly equal proportions from high-fructose corn syrup (also known as isoglucose in Europe) or sucrose. The purpose of this review is to present data from recent RCTs and findings from recent systematic reviews and meta-analyses related to sugar consumption and its putative health effects. This review evaluates findings from recent randomized controlled trials, systematic reviews and meta-analyses into the relationship of sugar consumption and a range of health-related issues including energy-regulating hormones, obesity, cardiovascular disease, diabetes, and accumulation of liver fat and neurologic responses. Data from these sources do not support linkages between sugar consumption at normal levels within the human diet and various adverse metabolic and health-related effects.

Novel application of the MSSCP method in biodiversity studies.

PubMed

Tomczyk-Żak, Karolina; Kaczanowski, Szymon; Górecka, Magdalena; Zielenkiewicz, Urszula

2012-02-01

Analysis of 16S rRNA sequence diversity is widely performed for characterizing the biodiversity of microbial samples. The number of determined sequences has a considerable impact on complete results. Although the cost of mass sequencing is decreasing, it is often still too high for individual projects. We applied the multi-temperature single-strand conformational polymorphism (MSSCP) method to decrease the number of analysed sequences. This was a novel application of this method. As a control, the same sample was analysed using random sequencing. In this paper, we adapted the MSSCP technique for screening of unique sequences of the 16S rRNA gene library and bacterial strains isolated from biofilms growing on the walls of an ancient gold mine in Poland and determined whether the results obtained by both methods differed and whether random sequencing could be replaced by MSSCP. Although it was biased towards the detection of rare sequences in the samples, the qualitative results of MSSCP were not different than those of random sequencing. Unambiguous discrimination of unique clones and strains creates an opportunity to effectively estimate the biodiversity of natural communities, especially in populations which are numerous but species poor. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples.

PubMed Central

Peto, R.; Pike, M. C.; Armitage, P.; Breslow, N. E.; Cox, D. R.; Howard, S. V.; Mantel, N.; McPherson, K.; Peto, J.; Smith, P. G.

1977-01-01

Part I of this report appeared in the previous issue (Br. J. Cancer (1976) 34,585), and discussed the design of randomized clinical trials. Part II now describes efficient methods of analysis of randomized clinical trials in which we wish to compare the duration of survival (or the time until some other untoward event first occurs) among different groups of patients. It is intended to enable physicians without statistical training either to analyse such data themselves using life tables, the logrank test and retrospective stratification, or, when such analyses are presented, to appreciate them more critically, but the discussion may also be of interest to statisticians who have not yet specialized in clinical trial analyses. PMID:831755

Unidentified Language Deficits in Children with Emotional and Behavioral Disorders: A Meta-Analysis

ERIC Educational Resources Information Center

Hollo, Alexandra; Wehby, Joseph H.; Oliver, Regina M.

2014-01-01

Low language proficiency and problem behavior often co-occur, yet language deficits are likely to be overlooked in children with emotional and behavioral disorders (EBD). Random effects meta-analyses were conducted to determine prevalence and severity of the problem. Across 22 studies, participants included 1,171 children ages 5-13 with formally…

Using Multivariate Generalizability Theory to Assess the Effect of Content Stratification on the Reliability of a Performance Assessment

ERIC Educational Resources Information Center

Keller, Lisa A.; Clauser, Brian E.; Swanson, David B.

2010-01-01

In recent years, demand for performance assessments has continued to grow. However, performance assessments are notorious for lower reliability, and in particular, low reliability resulting from task specificity. Since reliability analyses typically treat the performance tasks as randomly sampled from an infinite universe of tasks, these estimates…

Vicarious Trauma: An Exploratory Study of the Impact of Providing Sexual Abuse Treatment on Clinicians' Trust and Intimacy

ERIC Educational Resources Information Center

VanDeusen, Karen M.; Way, Ineke

2006-01-01

This study examined vicarious trauma effects in male and female clinicians who treat sexual abuse survivors (n = 111) and sexual offenders (n = 272). The national survey was conducted using a random sample of clinical members of two professional organizations. Analyses tested the relationships between demographic variables, maltreatment history,…

Secondary prevention of work-related disability in nonspecific low back pain: does problem-solving therapy help? A randomized clinical trial.

PubMed

van den Hout, Johanna H C; Vlaeyen, Johan W S; Heuts, Peter H T G; Zijlema, Johan H L; Wijnen, Joseph A G

2003-01-01

Given the individual and economic burden of chronic work disability in low back pain patients, there is a need for effective preventive interventions. The aim of the present study was to investigate whether problem-solving therapy had a supplemental value when added to behavioral graded activity, regarding days of sick leave and work status. Randomized controlled trial. Employees who were recently on sick leave as a result of nonspecific low back pain were referred to the rehabilitation center by general practitioner, occupational physician, or rehabilitation physician. Forty-five employees had been randomly assigned to the experimental treatment condition that included behavioral graded activity and problem-solving therapy (GAPS), and 39 employees had been randomly assigned to behavioral graded activity and group education (GAGE). Days of sick leave and work status. Data were retrieved from occupational health services. Data analyses showed that employees in the GAPS group had significantly fewer days of sick leave in the second half-year after the intervention. Moreover, work status was more favorable for employees in this condition, in that more employees had a 100% return-to-work and fewer patients ended up receiving disability pensions one year after the intervention. Sensitivity analyses confirmed these results. The addition of problem-solving therapy to behavioral graded activity had supplemental value in employees with nonspecific low back pain.

Meta-analysis of randomized controlled trials comparing 17α-hydroxyprogesterone caproate and vaginal progesterone for the prevention of recurrent spontaneous preterm delivery.

PubMed

Oler, Elizabeth; Eke, Ahizechukwu C; Hesson, Ashley

2017-07-01

Vaginal progesterone and 17α-hydroxyprogesterone (17α-OHP) are both used to prevent preterm delivery in women who have experienced spontaneous preterm delivery (SPTD) previously. Randomized trial data of the comparative effectiveness of these interventions have been mixed. To compare the efficacy of intramuscular 17α-OHP and vaginal progesterone in the prevention of recurrent SPTD. Cochrane Central Register of Controlled Trials, African Journals Online, Embase, Google Scholar, ISI Web of Science, LILACS, CINAHL, PubMed, and registers of ongoing trials were searched using keywords related to 17α-OHP, vaginal progesterone, and preterm delivery. Randomized controlled trials published between January 1, 1966, and November 30, 2016, comparing 17α-OHP and vaginal progesterone for the prevention of recurrent SPTD during singleton pregnancies were included. Study data were extracted and meta-analyses were performed when outcomes were comparable. The meta-analyses included data from three randomized trials. Lower rates of SPTD before 34 weeks (relative risk 0.71, 95% confidence interval 0.53-0.95) and before 32 weeks (relative risk 0.62, 95% confidence interval 0.40-0.94) of pregnancy were observed among patients treated with vaginal progesterone. Vaginal progesterone and 17α-OHP were comparable for the prevention of recurrent SPTD in singleton pregnancies; vaginal progesterone could be superior. © 2017 International Federation of Gynecology and Obstetrics.

Effects of a price increase on purchases of sugar sweetened beverages. Results from a randomized controlled trial.

PubMed

Waterlander, Wilma Elzeline; Ni Mhurchu, Cliona; Steenhuis, Ingrid H M

2014-07-01

Sugar sweetened beverage (SSB) taxes are receiving increased political interest. However, there have been no experimental studies of the effects of price increases on SSBs or the effects on close substitutes such as diet drinks, alcohol or sugary snacks. Therefore, the aim of this study was to examine the effects of a price increase on SSBs on beverage and snack purchases using a randomized controlled design within a three-dimensional web-based supermarket. The trial contained two conditions: experimental condition with a 19% tax on SSBs (to reflect an increase in Dutch value added tax from 6% to 19%); and a control condition with regular prices. N = 102 participants were randomized and purchased groceries on a single occasion at a three-dimensional Virtual Supermarket. Data were analysed using independent t-tests and regression analysis. Results showed that participants in the price increase condition purchased significantly less SSBs than the control group (B = -.90; 95% CI = -1.70 to -.10 L per household per week). There were no significant effects on purchases in other beverage or snack food categories. This means that the higher VAT rate was effective in reducing SSB purchases and had no negative side-effects. Copyright © 2014. Published by Elsevier Ltd.

An examination of mediators of the transfer of cognitive speed of processing training to everyday functional performance.

PubMed

Edwards, Jerri D; Ruva, Christine L; O'Brien, Jennifer L; Haley, Christine B; Lister, Jennifer J

2013-06-01

The purpose of these analyses was to examine mediators of the transfer of cognitive speed of processing training to improved everyday functional performance (J. D. Edwards, V. G. Wadley,, D. E. Vance, D. L. Roenker, & K. K. Ball, 2005, The impact of speed of processing training on cognitive and everyday performance. Aging & Mental Health, 9, 262-271). Cognitive speed of processing and visual attention (as measured by the Useful Field of View Test; UFOV) were examined as mediators of training transfer. Secondary data analyses were conducted from the Staying Keen in Later Life (SKILL) study, a randomized cohort study including 126 community dwelling adults 63 to 87 years of age. In the SKILL study, participants were randomized to an active control group or cognitive speed of processing training (SOPT), a nonverbal, computerized intervention involving perceptual practice of visual tasks. Prior analyses found significant effects of training as measured by the UFOV and Timed Instrumental Activities of Daily Living (TIADL) Tests. Results from the present analyses indicate that speed of processing for a divided attention task significantly mediated the effect of SOPT on everyday performance (e.g., TIADL) in a multiple mediation model accounting for 91% of the variance. These findings suggest that everyday functional improvements found from SOPT are directly attributable to improved UFOV performance, speed of processing for divided attention in particular. Targeting divided attention in cognitive interventions may be important to positively affect everyday functioning among older adults. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Inference for binomial probability based on dependent Bernoulli random variables with applications to meta‐analysis and group level studies

PubMed Central

Bakbergenuly, Ilyas; Morgenthaler, Stephan

2016-01-01

We study bias arising as a result of nonlinear transformations of random variables in random or mixed effects models and its effect on inference in group‐level studies or in meta‐analysis. The findings are illustrated on the example of overdispersed binomial distributions, where we demonstrate considerable biases arising from standard log‐odds and arcsine transformations of the estimated probability p^, both for single‐group studies and in combining results from several groups or studies in meta‐analysis. Our simulations confirm that these biases are linear in ρ, for small values of ρ, the intracluster correlation coefficient. These biases do not depend on the sample sizes or the number of studies K in a meta‐analysis and result in abysmal coverage of the combined effect for large K. We also propose bias‐correction for the arcsine transformation. Our simulations demonstrate that this bias‐correction works well for small values of the intraclass correlation. The methods are applied to two examples of meta‐analyses of prevalence. PMID:27192062

Fluoride toothpastes for preventing dental caries in children and adolescents.

PubMed

Marinho, V C; Higgins, J P; Sheiham, A; Logan, S

2003-01-01

Fluoride toothpastes have been widely used for over three decades and remain a benchmark intervention for the prevention of dental caries. To determine the effectiveness and safety of fluoride toothpastes in the prevention of caries in children and to examine factors potentially modifying their effect. We searched the Cochrane Oral Health Group's Trials Register (May 2000), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2000), MEDLINE (1966 to January 2000), plus several other databases. We handsearched journals, reference lists of articles and contacted selected authors and manufacturers. Randomized or quasi-randomized controlled trials with blind outcome assessment, comparing fluoride toothpaste with placebo in children up to 16 years during at least one year. The main outcome was caries increment measured by the change in decayed, missing and filled tooth surfaces (D(M)FS). Inclusion decisions, quality assessment and data extraction were duplicated in a random sample of one third of studies, and consensus achieved by discussion or a third party. Authors were contacted for missing data. The primary measure of effect was the prevented fraction (PF) that is the difference in caries increments between the treatment and control groups expressed as a percentage of the increment in the control group. Random effects meta-analyses were performed where data could be pooled. Potential sources of heterogeneity were examined in random effects meta-regression analyses. Seventy-four studies were included. For the 70 that contributed data for meta-analysis (involving 42,300 children) the D(M)FS pooled PF was 24% (95% confidence interval (CI), 21 to 28%; p<0.0001). This means that 1.6 children need to brush with a fluoride toothpaste (rather than a non-fluoride toothpaste) over three years to prevent one D(M)FS in populations with caries increment of 2.6 D(M)FS per year. In populations with caries increment of 1.1 D(M)FS per year, 3.7 children will need to use a fluoride toothpaste for three years to avoid one D(M)FS. There was clear heterogeneity, confirmed statistically (p<0.0001). The effect of fluoride toothpaste increased with higher baseline levels of D(M)FS, higher fluoride concentration, higher frequency of use, and supervised brushing, but was not influenced by exposure to water fluoridation. There is little information concerning the deciduous dentition or adverse effects (fluorosis). Supported by more than half a century of research, the benefits of fluoride toothpastes are firmly established. Taken together, the trials are of relatively high quality, and provide clear evidence that fluoride toothpastes are efficacious in preventing caries.

A Novel Motion Compensation Method for Random Stepped Frequency Radar with M-sequence

NASA Astrophysics Data System (ADS)

Liao, Zhikun; Hu, Jiemin; Lu, Dawei; Zhang, Jun

2018-01-01

The random stepped frequency radar is a new kind of synthetic wideband radar. In the research, it has been found that it possesses a thumbtack-like ambiguity function which is considered to be the ideal one. This also means that only a precise motion compensation could result in the correct high resolution range profile. In this paper, we will introduce the random stepped frequency radar coded by M-sequence firstly and briefly analyse the effect of relative motion between target and radar on the distance imaging, which is called defocusing problem. Then, a novel motion compensation method, named complementary code cancellation, will be put forward to solve this problem. Finally, the simulated experiments will demonstrate its validity and the computational analysis will show up its efficiency.

Efficacy and safety of ginger in osteoarthritis patients: a meta-analysis of randomized placebo-controlled trials.

PubMed

Bartels, E M; Folmer, V N; Bliddal, H; Altman, R D; Juhl, C; Tarp, S; Zhang, W; Christensen, R

2015-01-01

The aim of this study was to assess the clinical efficacy and safety of oral ginger for symptomatic treatment of osteoarthritis (OA) by carrying out a systematic literature search followed by meta-analyses on selected studies. Inclusion criteria were randomized controlled trials (RCTs) comparing oral ginger treatment with placebo in OA patients aged >18 years. Outcomes were reduction in pain and reduction in disability. Harm was assessed as withdrawals due to adverse events. The efficacy effect size was estimated using Hedges' standardized mean difference (SMD), and safety by risk ratio (RR). Standard random-effects meta-analysis was used, and inconsistency was evaluated by the I-squared index (I(2)). Out of 122 retrieved references, 117 were discarded, leaving five trials (593 patients) for meta-analyses. The majority reported relevant randomization procedures and blinding, but an inadequate intention-to-treat (ITT) analysis. Following ginger intake, a statistically significant pain reduction SMD = -0.30 ([95% CI: [(-0.50, -0.09)], P = 0.005]) with a low degree of inconsistency among trials (I(2) = 27%), and a statistically significant reduction in disability SMD = -0.22 ([95% CI: ([-0.39, -0.04)]; P = 0.01; I(2) = 0%]) were seen, both in favor of ginger. Patients given ginger were more than twice as likely to discontinue treatment compared to placebo ([RR = 2.33; 95% CI: (1.04, 5.22)]; P = 0.04; I(2) = 0%]). Ginger was modestly efficacious and reasonably safe for treatment of OA. We judged the evidence to be of moderate quality, based on the small number of participants and inadequate ITT populations. Prospero: CRD42011001777. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Effectiveness of a two-step population-based osteoporosis screening program using FRAX: the randomized Risk-stratified Osteoporosis Strategy Evaluation (ROSE) study.

PubMed

Rubin, K H; Rothmann, M J; Holmberg, T; Høiberg, M; Möller, S; Barkmann, R; Glüer, C C; Hermann, A P; Bech, M; Gram, J; Brixen, K

2018-03-01

The Risk-stratified Osteoporosis Strategy Evaluation (ROSE) study investigated the effectiveness of a two-step screening program for osteoporosis in women. We found no overall reduction in fractures from systematic screening compared to the current case-finding strategy. The group of moderate- to high-risk women, who accepted the invitation to DXA, seemed to benefit from the program. The purpose of the ROSE study was to investigate the effectiveness of a two-step population-based osteoporosis screening program using the Fracture Risk Assessment Tool (FRAX) derived from a self-administered questionnaire to select women for DXA scan. After the scanning, standard osteoporosis management according to Danish national guidelines was followed. Participants were randomized to either screening or control group, and randomization was stratified according to age and area of residence. Inclusion took place from February 2010 to November 2011. Participants received a self-administered questionnaire, and women in the screening group with a FRAX score ≥ 15% (major osteoporotic fractures) were invited to a DXA scan. Primary outcome was incident clinical fractures. Intention-to-treat analysis and two per-protocol analyses were performed. A total of 3416 fractures were observed during a median follow-up of 5 years. No significant differences were found in the intention-to-treat analyses with 34,229 women included aged 65-80 years. The per-protocol analyses showed a risk reduction in the group that underwent DXA scanning compared to women in the control group with a FRAX ≥ 15%, in regard to major osteoporotic fractures, hip fractures, and all fractures. The risk reduction was most pronounced for hip fractures (adjusted SHR 0.741, p = 0.007). Compared to an office-based case-finding strategy, the two-step systematic screening strategy had no overall effect on fracture incidence. The two-step strategy seemed, however, to be beneficial in the group of women who were identified by FRAX as moderate- or high-risk patients and complied with DXA.

A Bayesian ridge regression analysis of congestion's impact on urban expressway safety.

PubMed

Shi, Qi; Abdel-Aty, Mohamed; Lee, Jaeyoung

2016-03-01

With the rapid growth of traffic in urban areas, concerns about congestion and traffic safety have been heightened. This study leveraged both Automatic Vehicle Identification (AVI) system and Microwave Vehicle Detection System (MVDS) installed on an expressway in Central Florida to explore how congestion impacts the crash occurrence in urban areas. Multiple congestion measures from the two systems were developed. To ensure more precise estimates of the congestion's effects, the traffic data were aggregated into peak and non-peak hours. Multicollinearity among traffic parameters was examined. The results showed the presence of multicollinearity especially during peak hours. As a response, ridge regression was introduced to cope with this issue. Poisson models with uncorrelated random effects, correlated random effects, and both correlated random effects and random parameters were constructed within the Bayesian framework. It was proven that correlated random effects could significantly enhance model performance. The random parameters model has similar goodness-of-fit compared with the model with only correlated random effects. However, by accounting for the unobserved heterogeneity, more variables were found to be significantly related to crash frequency. The models indicated that congestion increased crash frequency during peak hours while during non-peak hours it was not a major crash contributing factor. Using the random parameter model, the three congestion measures were compared. It was found that all congestion indicators had similar effects while Congestion Index (CI) derived from MVDS data was a better congestion indicator for safety analysis. Also, analyses showed that the segments with higher congestion intensity could not only increase property damage only (PDO) crashes, but also more severe crashes. In addition, the issues regarding the necessity to incorporate specific congestion indicator for congestion's effects on safety and to take care of the multicollinearity between explanatory variables were also discussed. By including a specific congestion indicator, the model performance significantly improved. When comparing models with and without ridge regression, the magnitude of the coefficients was altered in the existence of multicollinearity. These conclusions suggest that the use of appropriate congestion measure and consideration of multicolilnearity among the variables would improve the models and our understanding about the effects of congestion on traffic safety. Copyright © 2015 Elsevier Ltd. All rights reserved.

Analysis of Palm Oil Production, Export, and Government Consumption to Gross Domestic Product of Five Districts in West Kalimantan by Panel Regression

NASA Astrophysics Data System (ADS)

Sulistianingsih, E.; Kiftiah, M.; Rosadi, D.; Wahyuni, H.

2017-04-01

Gross Domestic Product (GDP) is an indicator of economic growth in a region. GDP is a panel data, which consists of cross-section and time series data. Meanwhile, panel regression is a tool which can be utilised to analyse panel data. There are three models in panel regression, namely Common Effect Model (CEM), Fixed Effect Model (FEM) and Random Effect Model (REM). The models will be chosen based on results of Chow Test, Hausman Test and Lagrange Multiplier Test. This research analyses palm oil about production, export, and government consumption to five district GDP are in West Kalimantan, namely Sanggau, Sintang, Sambas, Ketapang and Bengkayang by panel regression. Based on the results of analyses, it concluded that REM, which adjusted-determination-coefficient is 0,823, is the best model in this case. Also, according to the result, only Export and Government Consumption that influence GDP of the districts.

Vascular protection in peripheral artery disease: systematic review and modelling study.

PubMed

Hackam, D G; Sultan, N M; Criqui, M H

2009-07-01

To ascertain the effectiveness of medical therapy for reducing risk in peripheral artery disease (PAD) and to model the potential impact of combining multiple efficacious approaches. 17 electronic databases, reference lists of primary studies, clinical practice guidelines, review articles, trial registries and conference proceedings from cardiology, vascular surgery and atherosclerosis meetings were screened. Eligible studies were randomized trials or meta-analyses of randomized trials of medical therapy for PAD which reported major cardiovascular events (myocardial infarction, stroke and cardiovascular death). Baseline event rates for modelling analyses were derived from published natural history cohorts. Overall, three strategies had persuasive evidence for reducing risk in PAD: antiplatelet agents (pooled RRR 26%, 95% CI 10 to 42), statins (pooled RRR 26%, 95% CI 18 to 33) and angiotensin-converting enzyme inhibitors (individual trial RRR 25%, 95% CI 8 to 39). The estimated cumulative relative risk reduction for all three strategies was 59% (CI 32 to 76). Given a 5-year major cardiovascular event rate of 25%, the corresponding absolute risk reduction and number needed to treat to prevent one event were 15% (CI 8 to 19) and 7 (CI 5 to 12), respectively. Population level analyses suggest that increased uptake of these modalities could prevent more than 200 000 events in patients with PAD each year. The use of multiple efficacious strategies has the potential to substantially reduce the cardiovascular burden of PAD. However, these data should be regarded as hypothetical, since they are based on mathematical modelling rather than factorial randomized trials.

Effect of UV irradiation on cutaneous cicatrices: a randomized, controlled trial with clinical, skin reflectance, histological, immunohistochemical and biochemical evaluations.

PubMed

Due, Eva; Rossen, Kristian; Sorensen, Lars Tue; Kliem, Anette; Karlsmark, Tonny; Haedersdal, Merete

2007-01-01

The aim of this study was to examine the effect of ultraviolet (UV) irradiation on human cutaneous cicatrices. In this randomized, controlled study, dermal punch biopsy wounds served as a wound healing model. Wounds healed by primary or second intention and were randomized to postoperative solar UV irradiation or to no UV exposure. Evaluations after 5 and 12 weeks included blinded clinical assessments, skin reflectance measurements, histology, immunohistochemistry, and biochemical analyses of the N-terminal propeptide from procollagen-1, hydroxyproline, hydroxylysine, and proline. Twelve weeks postoperatively, UV-irradiated cicatrices healing by second intention: (i) were significantly pointed out as the most disfiguring; (ii) obtained significantly higher scores of colour, infiltration and cicatrix area; and (iii) showed significantly higher increase in skin-reflectance measurements of skin-pigmentation vs. non-irradiated cicatrices. No histological, immunohistochemical or biochemical differences were found. In conclusion, postoperative UV exposure aggravates the clinical appearance of cicatrices in humans.

Detection of mastitis in dairy cattle by use of mixture models for repeated somatic cell scores: a Bayesian approach via Gibbs sampling.

PubMed

Odegård, J; Jensen, J; Madsen, P; Gianola, D; Klemetsdal, G; Heringstad, B

2003-11-01

The distribution of somatic cell scores could be regarded as a mixture of at least two components depending on a cow's udder health status. A heteroscedastic two-component Bayesian normal mixture model with random effects was developed and implemented via Gibbs sampling. The model was evaluated using datasets consisting of simulated somatic cell score records. Somatic cell score was simulated as a mixture representing two alternative udder health statuses ("healthy" or "diseased"). Animals were assigned randomly to the two components according to the probability of group membership (Pm). Random effects (additive genetic and permanent environment), when included, had identical distributions across mixture components. Posterior probabilities of putative mastitis were estimated for all observations, and model adequacy was evaluated using measures of sensitivity, specificity, and posterior probability of misclassification. Fitting different residual variances in the two mixture components caused some bias in estimation of parameters. When the components were difficult to disentangle, so were their residual variances, causing bias in estimation of Pm and of location parameters of the two underlying distributions. When all variance components were identical across mixture components, the mixture model analyses returned parameter estimates essentially without bias and with a high degree of precision. Including random effects in the model increased the probability of correct classification substantially. No sizable differences in probability of correct classification were found between models in which a single cow effect (ignoring relationships) was fitted and models where this effect was split into genetic and permanent environmental components, utilizing relationship information. When genetic and permanent environmental effects were fitted, the between-replicate variance of estimates of posterior means was smaller because the model accounted for random genetic drift.

The effect of perhexiline on myocardial protection during coronary artery surgery: a two-centre, randomized, double-blind, placebo-controlled trial

PubMed Central

Drury, Nigel E.; Howell, Neil J.; Calvert, Melanie J.; Weber, Ralf J.M.; Senanayake, Eshan L.; Lewis, Michael E.; Hyde, Jonathan A.J.; Green, David H.; Mascaro, Jorge G.; Wilson, Ian C.; Graham, Timothy R.; Rooney, Stephen J.; Viant, Mark R.; Freemantle, Nick; Frenneaux, Michael P.; Pagano, Domenico

2015-01-01

OBJECTIVES Perhexiline is thought to modulate metabolism by inhibiting mitochondrial carnitine palmitoyltransferase-1, reducing fatty acid uptake and increasing carbohydrate utilization. This study assessed whether preoperative perhexiline improves markers of myocardial protection in patients undergoing coronary artery bypass graft surgery and analysed its effect on the myocardial metabolome. METHODS In a prospective, randomized, double-blind, placebo-controlled trial, patients at two centres were randomized to receive either oral perhexiline or placebo for at least 5 days prior to surgery. The primary outcome was a low cardiac output episode in the first 6 h. All pre-specified analyses were conducted according to the intention-to-treat principle with a statistical power of 90% to detect a relative risk of 0.5 and a conventional one-sided α-value of 0.025. A subset of pre-ischaemic left ventricular biopsies was analysed using mass spectrometry-based metabolomics. RESULTS Over a 3-year period, 286 patients were randomized, received the intervention and were included in the analysis. The incidence rate of a low cardiac output episode in the perhexiline arm was 36.7% (51/139) vs 34.7% (51/147) in the control arm [odds ratio (OR) 0.92, 95% confidence interval (CI) 0.56–1.50, P = 0.74]. Perhexiline was associated with a reduction in the cardiac index at 6 h [difference in means 0.19, 95% CI 0.07–0.31, P = 0.001] and an increase in inotropic support in the first 12 h (OR 0.55, 95% CI 0.34–0.89, P = 0.015). There were no significant differences in myocardial injury with troponin-T or electrocardiogram, reoperation, renal dysfunction or length of stay. No difference in the preischaemic left ventricular metabolism was identified between groups on metabolomics analysis. CONCLUSIONS Preoperative perhexiline does not improve myocardial protection in patients undergoing coronary surgery and in fact reduced perioperative cardiac output, increasing the need for inotropic support. Perhexiline has no significant effect on the mass spectrometry-visible polar myocardial metabolome in vivo in humans, supporting the suggestion that it acts via a pathway that is independent of myocardial carnitine palmitoyltransferase inhibition and may explain the lack of clinical benefit observed following surgery. ClinicalTrials.Gov ID NCT00845364. PMID:24948413

The effect of small solar powered 'Bͻkͻͻ' net fans on mosquito net use: results from a randomized controlled cross-over trial in southern Ghana.

PubMed

Briët, Olivier J T; Yukich, Joshua O; Pfeiffer, Constanze; Miller, William; Jaeger, Mulako S; Khanna, Nitin; Oppong, Samuel; Nardini, Peter; Ahorlu, Collins K; Keating, Joseph

2017-01-03

Long-lasting insecticidal nets (LLINs) are ineffective malaria transmission prevention tools if they are unused. Discomfort due to heat is the most commonly reported reason for not using nets, but this problem is largely unaddressed. With increasing rural electrification and the dropping price of solar power, fans could improve comfort inside nets and be affordable to populations in malaria endemic areas. Here, results are presented from a pilot randomized controlled cross-over study testing the effect of fans on LLIN use. Eighty-three households from two rural communities in Greater Accra, Ghana, randomized into three groups, participated in a 10-month cross-over trial. After a screening survey to identify eligible households, all households received new LLINs. Bͻkͻͻ net fan systems (one fan per member) were given to households in Group 1 and water filters were given to households in Group 2. At mid-point, Group 1 and 2 crossed over interventions. Households in Group 1 and 2 participated in fortnightly surveys on households' practices related to nets, fans and water filters, while households in Group 3 were surveyed only at screening, mid-point and study end. Entomological and weather data were collected throughout the study. Analysis took both 'per protocol' (PP) and 'intention to treat' (ITT) approaches. The mid- and end-point survey data from Group 1 and 2 were analysed using Firth logistic regressions. Fortnightly survey data from all groups were analysed using logistic regressions with random effects. Provision of fans to households appeared to increase net use in this study. Although the increase in net use explained by fans was not significant in the primary analyses (ITT odds ratio 3.24, p > 0.01; PP odds ratio = 1.17, p > 0.01), it was significant in secondary PP analysis (odds ratio = 1.95, p < 0.01). Net use was high at screening and even higher after provision of new LLINs and with follow up. Fan use was 90-100% depending on the fortnightly visit. This pilot study could not provide definitive evidence that fans increase net use. A larger study with additional statistical power is needed to assess this association across communities with diverse environmental and socio-demographic characteristics.

The effect of perhexiline on myocardial protection during coronary artery surgery: a two-centre, randomized, double-blind, placebo-controlled trial.

PubMed

Drury, Nigel E; Howell, Neil J; Calvert, Melanie J; Weber, Ralf J M; Senanayake, Eshan L; Lewis, Michael E; Hyde, Jonathan A J; Green, David H; Mascaro, Jorge G; Wilson, Ian C; Graham, Timothy R; Rooney, Stephen J; Viant, Mark R; Freemantle, Nick; Frenneaux, Michael P; Pagano, Domenico

2015-03-01

Perhexiline is thought to modulate metabolism by inhibiting mitochondrial carnitine palmitoyltransferase-1, reducing fatty acid uptake and increasing carbohydrate utilization. This study assessed whether preoperative perhexiline improves markers of myocardial protection in patients undergoing coronary artery bypass graft surgery and analysed its effect on the myocardial metabolome. In a prospective, randomized, double-blind, placebo-controlled trial, patients at two centres were randomized to receive either oral perhexiline or placebo for at least 5 days prior to surgery. The primary outcome was a low cardiac output episode in the first 6 h. All pre-specified analyses were conducted according to the intention-to-treat principle with a statistical power of 90% to detect a relative risk of 0.5 and a conventional one-sided α-value of 0.025. A subset of pre-ischaemic left ventricular biopsies was analysed using mass spectrometry-based metabolomics. Over a 3-year period, 286 patients were randomized, received the intervention and were included in the analysis. The incidence rate of a low cardiac output episode in the perhexiline arm was 36.7% (51/139) vs 34.7% (51/147) in the control arm [odds ratio (OR) 0.92, 95% confidence interval (CI) 0.56-1.50, P = 0.74]. Perhexiline was associated with a reduction in the cardiac index at 6 h [difference in means 0.19, 95% CI 0.07-0.31, P = 0.001] and an increase in inotropic support in the first 12 h (OR 0.55, 95% CI 0.34-0.89, P = 0.015). There were no significant differences in myocardial injury with troponin-T or electrocardiogram, reoperation, renal dysfunction or length of stay. No difference in the preischaemic left ventricular metabolism was identified between groups on metabolomics analysis. Preoperative perhexiline does not improve myocardial protection in patients undergoing coronary surgery and in fact reduced perioperative cardiac output, increasing the need for inotropic support. Perhexiline has no significant effect on the mass spectrometry-visible polar myocardial metabolome in vivo in humans, supporting the suggestion that it acts via a pathway that is independent of myocardial carnitine palmitoyltransferase inhibition and may explain the lack of clinical benefit observed following surgery. NCT00845364. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.

Economic Evaluation of a Web-Based Guided Self-Help Intervention for Employees With Depressive Symptoms: Results of a Randomized Controlled Trial.

PubMed

Geraedts, Anna S; van Dongen, Johanna M; Kleiboer, Annet M; Wiezer, Noortje M; van Mechelen, Willem; Cuijpers, Pim; Bosmans, Judith E

2015-06-01

To evaluate the cost-effectiveness of a Web-based guided intervention compared with care as usual for employees with depressive symptoms. A total of 231 employees with depressive symptoms were randomized. Data were collected at baseline, 8 weeks, 6 months, and 12 months. Analyses were conducted from the societal and employer's perspective. At 12 months, a significant intervention effect on depressive symptoms was found. At a willingness to pay of 0 (€/unit of effect), the intervention's probabilities of cost-effectiveness were 0.62 (societal perspective) and 0.55 (employer's perspective). There was a 0.63 probability that the intervention resulted in a positive financial return for the employer. The intervention's cost-effectiveness with regard to depressive symptoms depends on the willingness to pay of societal and company decision makers as well as the probability of cost-effectiveness that they consider acceptable. The intervention is not cost-saving to the employer.

Effect of a Behavioral Self-Regulation Intervention on Patient Adherence to Fluid-Intake Restrictions in Hemodialysis: a Randomized Controlled Trial.

PubMed

Howren, M Bryant; Kellerman, Quinn D; Hillis, Stephen L; Cvengros, Jamie; Lawton, William; Christensen, Alan J

2016-04-01

The purpose of this study is to evaluate the efficacy of a behavioral self-regulation intervention vs. active control condition using a parallel-group randomized clinical trial with a sample of center hemodialysis patients with chronic kidney disease. Participants were recruited from 8 hemodialysis treatment centers in the Midwest. Eligible patients were (a) fluid nonadherent as defined by an interdialytic weight gain >2.5 kg over a 4-week period, (b) >18 years of age, (c) English-speaking without severe cognitive impairment, (d) treated with center-based hemodialysis for >3 months, and (e) not living in a care facility in which meals were managed. Medical records were used to identify eligible patients. Patients were randomly assigned to either a behavioral self-regulation intervention or active control condition in which groups of 3-8 patients met for hour-long, weekly sessions for 7 weeks at their usual hemodialysis clinic. Primary analyses were intention-to-treat. Sixty-one patients were randomized to the intervention while 58 were assigned to the attention-placebo support and discussion control. Covariate-adjusted between-subjects analyses demonstrated no unique intervention effect for the primary outcome, interdialytic weight gain (β = 0.13, p = 0.48). Significant within-subjects improvement over time was observed for the intervention group (β = -0.32, p = 0.014). The present study found that participation in a behavioral self-regulation intervention resulted in no unique intervention effect on a key indicator of adherence for those with severe chronic kidney disease. There was, however, modest within-subjects improvement in interdialytic weight gain for the intervention group which meshes with other evidence showing the utility of behavioral interventions in this patient population. ClinicalTrials.gov Identifier: NCT01066949.

Vitamin D and type 2 diabetes.

PubMed

Lips, Paul; Eekhoff, Marelise; van Schoor, Natasja; Oosterwerff, Mirjam; de Jongh, Renate; Krul-Poel, Yvonne; Simsek, Suat

2017-10-01

Vitamin D deficiency is associated with a decreased insulin release, insulin resistance and type 2 diabetes in experimental and epidemiological studies. Animal studies show that 1α,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) stimulates the pancreatic β-cell to secrete insulin. The relationship between vitamin D deficiency and insulin resistance could develop through inflammation, as vitamin D deficiency is associated with increased inflammatory markers. In addition, genetic polymorphisms of vitamin D -related genes may predispose to impaired glycemic control and type 2 diabetes. Epidemiologic studies showed an association between low serum 25-hydroxyvitamin D 3 (25(OH)D 3 ) concentration and an increased risk for the metabolic syndrome and type 2 diabetes. This may be partly explained by an increased fat mass. A possible causal relationship between vitamin D deficiency and type 2 diabetes should be proven by randomized clinical trials showing that either type 2 diabetes can be prevented or insulin release and insulin sensitivity can be improved by vitamin D supplements. The results of randomized clinical trials on the effect of vitamin D versus placebo, sometimes combined with calcium, in patients with impaired glucose tolerance ("prediabetes") or type 2 diabetes are inconsistent. Some studies showed a slight decrease of fasting plasma glucose or improvement of insulin resistance, but often only in posthoc analyses. These effects are mainly visible in patients with vitamin D deficiency and impaired glucose tolerance at baseline. Meta-analyses of randomized clinical trials in general did not show significant effects of vitamin D supplementation on glycemic control. Currently, several large scale randomized clinical trials with vitamin D supplementation in doses of 1600-4000IU/d are ongoing with glycemic control or incidence of diabetes mellitus as outcome. Vitamin D deficiency needs to be prevented or cured, but until the results of these trials are published, high-dose vitamin D supplementation cannot be recommended for prevention or amelioration of type 2 diabetes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Meta-Analysis of Cell-based CaRdiac stUdiEs (ACCRUE) in patients with acute myocardial infarction based on individual patient data.

PubMed

Gyöngyösi, Mariann; Wojakowski, Wojciech; Lemarchand, Patricia; Lunde, Ketil; Tendera, Michal; Bartunek, Jozef; Marban, Eduardo; Assmus, Birgit; Henry, Timothy D; Traverse, Jay H; Moyé, Lemuel A; Sürder, Daniel; Corti, Roberto; Huikuri, Heikki; Miettinen, Johanna; Wöhrle, Jochen; Obradovic, Slobodan; Roncalli, Jérome; Malliaras, Konstantinos; Pokushalov, Evgeny; Romanov, Alexander; Kastrup, Jens; Bergmann, Martin W; Atsma, Douwe E; Diederichsen, Axel; Edes, Istvan; Benedek, Imre; Benedek, Theodora; Pejkov, Hristo; Nyolczas, Noemi; Pavo, Noemi; Bergler-Klein, Jutta; Pavo, Imre J; Sylven, Christer; Berti, Sergio; Navarese, Eliano P; Maurer, Gerald

2015-04-10

The meta-Analysis of Cell-based CaRdiac study is the first prospectively declared collaborative multinational database, including individual data of patients with ischemic heart disease treated with cell therapy. We analyzed the safety and efficacy of intracoronary cell therapy after acute myocardial infarction (AMI), including individual patient data from 12 randomized trials (ASTAMI, Aalst, BOOST, BONAMI, CADUCEUS, FINCELL, REGENT, REPAIR-AMI, SCAMI, SWISS-AMI, TIME, LATE-TIME; n=1252). The primary end point was freedom from combined major adverse cardiac and cerebrovascular events (including all-cause death, AMI recurrance, stroke, and target vessel revascularization). The secondary end point was freedom from hard clinical end points (death, AMI recurrence, or stroke), assessed with random-effects meta-analyses and Cox regressions for interactions. Secondary efficacy end points included changes in end-diastolic volume, end-systolic volume, and ejection fraction, analyzed with random-effects meta-analyses and ANCOVA. We reported weighted mean differences between cell therapy and control groups. No effect of cell therapy on major adverse cardiac and cerebrovascular events (14.0% versus 16.3%; hazard ratio, 0.86; 95% confidence interval, 0.63-1.18) or death (1.4% versus 2.1%) or death/AMI recurrence/stroke (2.9% versus 4.7%) was identified in comparison with controls. No changes in ejection fraction (mean difference: 0.96%; 95% confidence interval, -0.2 to 2.1), end-diastolic volume, or systolic volume were observed compared with controls. These results were not influenced by anterior AMI location, reduced baseline ejection fraction, or the use of MRI for assessing left ventricular parameters. This meta-analysis of individual patient data from randomized trials in patients with recent AMI revealed that intracoronary cell therapy provided no benefit, in terms of clinical events or changes in left ventricular function. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01098591. © 2015 American Heart Association, Inc.

Meta-analysis: Smectite in the treatment of acute infectious diarrhoea in children.

PubMed

Szajewska, H; Dziechciarz, P; Mrukowicz, J

2006-01-15

Although not currently recommended, dioctahedral smectite (smectite) is commonly used to treat acute infectious diarrhoea in many countries. To evaluate systematically the effectiveness of smectite in treating acute infectious diarrhoea in children. Using medical subject headings and free-language terms, the following electronic databases were searched for studies relevant to acute infectious diarrhoea and smectite: MEDLINE, EMBASE, CINAHL and The Cochrane Library; additional references were obtained from reviewed articles. Only randomized-controlled trials were included. Nine randomized-controlled trials (1238 participants) met the inclusion criteria. Combined data from six randomized-controlled trials showed that smectite significantly reduced the duration of diarrhoea compared with placebo. The pooled weighted mean difference was (-22.7 h, 95% CI: -24.8 to -20.6) with a fixed model and remained significant in a random effect model (-24.4 h, 95% CI: -29.8 to -19.1). The chance of cure on intervention day 3 was significantly increased in the smectite vs. the control group (RR 1.64, 95% CI: 1.36-1.98; number needed to treat 4, 95% CI: 3-5). Adverse effects were similar in both groups. Smectite may be a useful adjunct to rehydration therapy in treating acute paediatric gastroenteritis. However, the results of this meta-analysis should be interpreted with caution as most of the included studies had important limitations. Cost-effectiveness analyses should be undertaken before routine pharmacological therapy with smectite is recommended.

Depression in type 2 diabetes mellitus: prevalence, impact, and treatment.

PubMed

Semenkovich, Katherine; Brown, Miriam E; Svrakic, Dragan M; Lustman, Patrick J

2015-04-01

Clinically significant depression is present in one of every four people with type 2 diabetes mellitus (T2DM). Depression increases the risk of the development of T2DM and the subsequent risks of hyperglycemia, insulin resistance, and micro- and macrovascular complications. Conversely, a diagnosis of T2DM increases the risk of incident depression and can contribute to a more severe course of depression. This linkage reflects a shared etiology consisting of complex bidirectional interactions among multiple variables, a process that may include autonomic and neurohormonal dysregulation, weight gain, inflammation, and hippocampal structural alterations. Two recent meta-analyses of randomized controlled depression treatment trials in patients with T2DM concluded that psychotherapy and antidepressant medication (ADM) were each moderately effective for depression and that cognitive behavior therapy (CBT) had beneficial effects on glycemic control. However, the number of studies (and patients exposed to randomized treatment) included in these analyses is extremely small and limits the certainty of conclusions that can be drawn from the data. Ultimately, there is no escaping the paucity of the evidence base and the need for additional controlled trials that specifically address depression management in T2DM. Future trials should determine both the effects of treatment and the change in depression during treatment on measures of mood, glycemic control, and medical outcome.

A systematic review and meta-analysis of carbohydrate benefits associated with randomized controlled competition-based performance trials.

PubMed

Pöchmüller, Martin; Schwingshackl, Lukas; Colombani, Paolo C; Hoffmann, Georg

2016-01-01

Carbohydrate supplements are widely used by athletes as an ergogenic aid before and during sports events. The present systematic review and meta-analysis aimed at synthesizing all available data from randomized controlled trials performed under real-life conditions. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched systematically up to February 2015. Study groups were categorized according to test mode and type of performance measurement. Subgroup analyses were done with reference to exercise duration and range of carbohydrate concentration. Random effects and fixed effect meta-analyses were performed using the Software package by the Cochrane Collaboration Review Manager 5.3. Twenty-four randomized controlled trials met the objectives and were included in the present systematic review, 16 of which provided data for meta-analyses. Carbohydrate supplementations were associated with a significantly shorter exercise time in groups performing submaximal exercise followed by a time trial [mean difference -0.9 min (95 % confidence interval -1.7, -0.2), p = 0.02] as compared to controls. Subgroup analysis showed that improvements were specific for studies administering a concentration of carbohydrates between 6 and 8 % [mean difference -1.0 min (95 % confidence interval -1.9, -0.0), p = 0.04]. Concerning groups with submaximal exercise followed by a time trial measuring power accomplished within a fixed time or distance, mean power output was significantly higher following carbohydrate load (mean difference 20.2 W (95 % confidence interval 9.0, 31.5), p = 0.0004]. Likewise, mean power output was significantly increased following carbohydrate intervention in groups with time trial measuring power within a fixed time or distance (mean difference 8.1 W (95 % confidence interval 0.5, 15.7) p = 0.04]. Due to the limitations of this systematic review, results can only be applied to a subset of athletes (trained male cyclists). For those, we could observe a potential ergogenic benefit of carbohydrate supplementation especially in a concentration range between 6 and 8 % when exercising longer than 90 min.

Clinical effectiveness of garlic (Allium sativum).

PubMed

Pittler, Max H; Ernst, Edzard

2007-11-01

The objective of this review is to update and assess the clinical evidence based on rigorous trials of the effectiveness of garlic (A. sativum). Systematic searches were carried out in Medline, Embase, Amed, the Cochrane Database of Systematic Reviews, Natural Standard, and the Natural Medicines Comprehensive Database (search date December 2006). Our own files, the bibliographies of relevant papers and the contents pages of all issues of the review journal FACT were searched for further studies. No language restrictions were imposed. To be included, trials were required to state that they were randomized and double blind. Systematic reviews and meta-analyses of garlic were included if based on the results of randomized, double-blind trials. The literature searches identified six relevant systematic reviews and meta-analysis and double-blind randomized trials (RCT) that were published subsequently. These relate to cancer, common cold, hypercholesterolemia, hypertension, peripheral arterial disease and pre-eclampsia. The evidence based on rigorous clinical trials of garlic is not convincing. For hypercholesterolemia, the reported effects are small and may therefore not be of clinical relevance. For reducing blood pressure, few studies are available and the reported effects are too small to be clinically meaningful. For all other conditions not enough data are available for clinical recommendations.

The effect of a health promotion intervention for construction workers on work-related outcomes: results from a randomized controlled trial.

PubMed

Viester, Laura; Verhagen, Evert A L M; Bongers, Paulien M; van der Beek, Allard J

2015-08-01

The objective of the present study is to investigate the effects of a worksite health promotion intervention on musculoskeletal symptoms, physical functioning, work ability, work-related vitality, work performance, and sickness absence. In a randomized controlled design, 314 construction workers were randomized into an intervention group (n = 162) receiving personal coaching, tailored information, and materials, and a control group (n = 152) receiving usual care. Sickness absence was recorded continuously in company records, and questionnaires were completed before, directly after the 6-month intervention period, and 12 months after baseline measurements. Linear and logistic regression analyses were performed to determine intervention effects. No significant changes at 6 or 12 months of follow-up were observed in musculoskeletal symptoms, physical functioning, work ability, work-related vitality, work performance, and sickness absence as a result of the intervention. This study shows that the intervention was not statistically significantly effective on secondary outcomes. Although the intervention improved physical activity, dietary, and weight-related outcomes, it was not successful in decreasing musculoskeletal symptoms and improving other work-related measures. Presumably, more multifaceted interventions are required to establish significant change in these outcomes.

Effective band structure of random III-V alloys

NASA Astrophysics Data System (ADS)

Popescu, Voicu; Zunger, Alex

2010-03-01

Random substitutional alloys have no long range order (LRO) or translational symmetry so rigorously speaking they have no E(k) band structure or manifestations thereof. Yet, many experiments on alloys are interpreted using the language of band theory, e.g. inferring Van Hove singularities, band dispersion and effective masses. Many standard alloy theories (VCA- or CPA-based) have the LRO imposed on the alloy Hamiltonian, assuming only on-site disorder, so they can not be used to judge the extent of LRO that really exists. We adopt the opposite way, by using large (thousand atom) randomly generated supercells in which chemically identical alloy atoms are allowed to have different local environments (a polymorphous representation). This then drives site-dependent atomic relaxation as well as potential fluctuations. The eigenstates from such supercells are then mapped onto the Brillouin zone (BZ) of the primitive cell, producing effective band dispersion. Results for (In,Ga)X show band-like behaviour only near the centre and faces of the BZ but rapidly lose such characteristics away from γ or for higher bands. We further analyse the effects of stoichiometry variation, internal relaxation, and short-range order on the alloy band structure.

Sequential change detection and monitoring of temporal trends in random-effects meta-analysis.

PubMed

Dogo, Samson Henry; Clark, Allan; Kulinskaya, Elena

2017-06-01

Temporal changes in magnitude of effect sizes reported in many areas of research are a threat to the credibility of the results and conclusions of meta-analysis. Numerous sequential methods for meta-analysis have been proposed to detect changes and monitor trends in effect sizes so that meta-analysis can be updated when necessary and interpreted based on the time it was conducted. The difficulties of sequential meta-analysis under the random-effects model are caused by dependencies in increments introduced by the estimation of the heterogeneity parameter τ 2 . In this paper, we propose the use of a retrospective cumulative sum (CUSUM)-type test with bootstrap critical values. This method allows retrospective analysis of the past trajectory of cumulative effects in random-effects meta-analysis and its visualization on a chart similar to CUSUM chart. Simulation results show that the new method demonstrates good control of Type I error regardless of the number or size of the studies and the amount of heterogeneity. Application of the new method is illustrated on two examples of medical meta-analyses. © 2016 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd. © 2016 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd.

The effects of rhythm control strategies versus rate control strategies for atrial fibrillation and atrial flutter: A systematic review with meta-analysis and Trial Sequential Analysis

PubMed Central

Gluud, Christian; Jakobsen, Janus C.

2017-01-01

Background Atrial fibrillation and atrial flutter may be managed by either a rhythm control strategy or a rate control strategy but the evidence on the clinical effects of these two intervention strategies is unclear. Our objective was to assess the beneficial and harmful effects of rhythm control strategies versus rate control strategies for atrial fibrillation and atrial flutter. Methods We searched CENTRAL, MEDLINE, Embase, LILACS, Web of Science, BIOSIS, Google Scholar, clinicaltrials.gov, TRIP, EU-CTR, Chi-CTR, and ICTRP for eligible trials comparing any rhythm control strategy with any rate control strategy in patients with atrial fibrillation or atrial flutter published before November 2016. Our primary outcomes were all-cause mortality, serious adverse events, and quality of life. Our secondary outcomes were stroke and ejection fraction. We performed both random-effects and fixed-effect meta-analysis and chose the most conservative result as our primary result. We used Trial Sequential Analysis (TSA) to control for random errors. Statistical heterogeneity was assessed by visual inspection of forest plots and by calculating inconsistency (I2) for traditional meta-analyses and diversity (D2) for TSA. Sensitivity analyses and subgroup analyses were conducted to explore the reasons for substantial statistical heterogeneity. We assessed the risk of publication bias in meta-analyses consisting of 10 trials or more with tests for funnel plot asymmetry. We used GRADE to assess the quality of the body of evidence. Results 25 randomized clinical trials (n = 9354 participants) were included, all of which were at high risk of bias. Meta-analysis showed that rhythm control strategies versus rate control strategies significantly increased the risk of a serious adverse event (risk ratio (RR), 1.10; 95% confidence interval (CI), 1.02 to 1.18; P = 0.02; I2 = 12% (95% CI 0.00 to 0.32); 21 trials), but TSA did not confirm this result (TSA-adjusted CI 0.99 to 1.22). The increased risk of a serious adverse event did not seem to be caused by any single component of the composite outcome. Meta-analysis showed that rhythm control strategies versus rate control strategies were associated with better SF-36 physical component score (mean difference (MD), 6.93 points; 95% CI, 2.25 to 11.61; P = 0.004; I2 = 95% (95% CI 0.94 to 0.96); 8 trials) and ejection fraction (MD, 4.20%; 95% CI, 0.54 to 7.87; P = 0.02; I2 = 79% (95% CI 0.69 to 0.85); 7 trials), but TSA did not confirm these results. Both meta-analysis and TSA showed no significant differences on all-cause mortality, SF-36 mental component score, Minnesota Living with Heart Failure Questionnaire, and stroke. Conclusions Rhythm control strategies compared with rate control strategies seem to significantly increase the risk of a serious adverse event in patients with atrial fibrillation. Based on current evidence, it seems that most patients with atrial fibrillation should be treated with a rate control strategy unless there are specific reasons (e.g., patients with unbearable symptoms due to atrial fibrillation or patients who are hemodynamically unstable due to atrial fibrillation) justifying a rhythm control strategy. More randomized trials at low risk of bias and low risk of random errors are needed. Trial registration PROSPERO CRD42016051433 PMID:29073191

Effects of the "Circle of Life" HIV-prevention program on marijuana use among American Indian middle school youths: a group randomized trial in a Northern Plains tribe.

PubMed

Asdigian, Nancy L; Whitesell, Nancy Rumbaugh; Keane, Ellen M; Mousseau, Alicia C; Kaufman, Carol E

2018-01-01

Early substance use threatens many American Indian/Alaska Native (AI/AN) communities, as it is a risk factor for maladaptive use and adverse health outcomes. Marijuana is among the first substances used by AI/AN youth, and its use becomes widespread during adolescence. Interventions that delay or reduce marijuana use hold the promise of curbing substance disorders and other health risk disparities in AI/AN populations. We evaluated the effectiveness of the Circle of Life (COL) program in reducing marijuana use among young AI adolescents. COL is a culturally tailored, theory-based human immunodeficiency virus (HIV) and sexually transmitted disease (STD) intervention shown to delay sexual initiation among AI youths. We conducted secondary analyses of data from a school-based group randomized trial conducted between 2006 and 2007 in all 13 middle schools on a rural, Northern Plains reservation (N = 635, 47% female). We used discrete-time survival analysis (DTSA) to assess COL effectiveness on risk of marijuana initiation among AI youths and latent growth curve modeling (LGCM) to evaluate effects on frequency of marijuana use over time. DTSA models showed that the overall risk of marijuana initiation was 17.3% lower in the COL group compared to the control group. No intervention effect on frequency of marijuana use emerged in LGCM analyses. COL is a multifaceted, culturally tailored, skills-based program effective in preventing marijuana uptake among AI youth.

Person mobility in the design and analysis of cluster-randomized cohort prevention trials.

PubMed

Vuchinich, Sam; Flay, Brian R; Aber, Lawrence; Bickman, Leonard

2012-06-01

Person mobility is an inescapable fact of life for most cluster-randomized (e.g., schools, hospitals, clinic, cities, state) cohort prevention trials. Mobility rates are an important substantive consideration in estimating the effects of an intervention. In cluster-randomized trials, mobility rates are often correlated with ethnicity, poverty and other variables associated with disparity. This raises the possibility that estimated intervention effects may generalize to only the least mobile segments of a population and, thus, create a threat to external validity. Such mobility can also create threats to the internal validity of conclusions from randomized trials. Researchers must decide how to deal with persons who leave study clusters during a trial (dropouts), persons and clusters that do not comply with an assigned intervention, and persons who enter clusters during a trial (late entrants), in addition to the persons who remain for the duration of a trial (stayers). Statistical techniques alone cannot solve the key issues of internal and external validity raised by the phenomenon of person mobility. This commentary presents a systematic, Campbellian-type analysis of person mobility in cluster-randomized cohort prevention trials. It describes four approaches for dealing with dropouts, late entrants and stayers with respect to data collection, analysis and generalizability. The questions at issue are: 1) From whom should data be collected at each wave of data collection? 2) Which cases should be included in the analyses of an intervention effect? and 3) To what populations can trial results be generalized? The conclusions lead to recommendations for the design and analysis of future cluster-randomized cohort prevention trials.

Effect of Nutrients, Dietary Supplements and Vitamins on Cognition: a Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Forbes, Scott C.; Holroyd-Leduc, Jayna M.; Poulin, Marc J.; Hogan, David B.

2015-01-01

Background Observational studies have suggested that various nutrients, dietary supplements, and vitamins may delay the onset of age-associated cognitive decline and dementia. We systematically reviewed recent randomized controlled trials investigating the effect of nutritional interventions on cognitive performance in older non-demented adults. Methods We searched MEDLINE, CINAHL, Embase, and the Cochrane Library for articles published between 2003 and 2013. We included randomized trials of ≥ 3 months’ duration that examined the cognitive effects of a nutritional intervention in non-demented adults > 40 years of age. Meta-analyses were done when sufficient trials were available. Results Twenty-four trials met inclusion criteria (six omega-3 fatty acids, seven B vitamins, three vitamin E, eight other interventions). In the meta-analyses, omega-3 fatty acids showed no significant effect on Mini-Mental State Examination (MMSE) scores (four trials, mean difference 0.06, 95% CI −0.08 – 0.19) or digit span forward (three trials, mean difference −0.02, 95% CI −0.30 – 0.25), while B vitamins showed no significant effect on MMSE scores (three trials, mean difference 0.02, 95% CI −0.22 – 0.25). None of the vitamin E studies reported significant effects on cognitive outcomes. Among the other nutritional interventions, statistically significant differences between the intervention and control groups on at least one cognitive domain were found in single studies of green tea extract, Concord grape juice, chromium picolinate, beta-carotene, two different combinations of multiple vitamins, and a dietary approach developed for the control of hypertension. Conclusions Omega-3 fatty acids, B vitamins, and vitamin E supplementation did not affect cognition in non-demented middle-aged and older adults. Other nutritional interventions require further evaluation before their use can be advocated for the prevention of age-associated cognitive decline and dementia. PMID:26740832

Exploring reasons for the observed inconsistent trial reports on intra-articular injections with hyaluronic acid in the treatment of osteoarthritis: Meta-regression analyses of randomized trials.

PubMed

Johansen, Mette; Bahrt, Henriette; Altman, Roy D; Bartels, Else M; Juhl, Carsten B; Bliddal, Henning; Lund, Hans; Christensen, Robin

2016-08-01

The aim was to identify factors explaining inconsistent observations concerning the efficacy of intra-articular hyaluronic acid compared to intra-articular sham/control, or non-intervention control, in patients with symptomatic osteoarthritis, based on randomized clinical trials (RCTs). A systematic review and meta-regression analyses of available randomized trials were conducted. The outcome, pain, was assessed according to a pre-specified hierarchy of potentially available outcomes. Hedges׳s standardized mean difference [SMD (95% CI)] served as effect size. REstricted Maximum Likelihood (REML) mixed-effects models were used to combine study results, and heterogeneity was calculated and interpreted as Tau-squared and I-squared, respectively. Overall, 99 studies (14,804 patients) met the inclusion criteria: Of these, only 71 studies (72%), including 85 comparisons (11,216 patients), had adequate data available for inclusion in the primary meta-analysis. Overall, compared with placebo, intra-articular hyaluronic acid reduced pain with an effect size of -0.39 [-0.47 to -0.31; P < 0.001], combining very heterogeneous trial findings (I(2) = 73%). The three most important covariates in reducing heterogeneity were overall risk of bias, blinding of personnel and trial size, reducing heterogeneity with 26%, 26%, and 25%, respectively (Interaction: P ≤ 0.001). Adjusting for publication/selective outcome reporting bias (by imputing "null effects") in 24 of the comparisons with no data available reduced the combined estimate to -0.30 [-0.36 to -0.23; P < 0.001] still in favor of hyaluronic acid. Based on available trial data, intra-articular hyaluronic acid showed a better effect than intra-articular saline on pain reduction in osteoarthritis. Publication bias and the risk of selective outcome reporting suggest only small clinical effect compared to saline. Copyright © 2016 Elsevier Inc. All rights reserved.

Cognitive Behavioral Insomnia Therapy for Those With Insomnia and Depression: A Randomized Controlled Clinical Trial

PubMed Central

Edinger, Jack D.; Kuchibhatla, Maragatha; Lachowski, Angela M.; Bogouslavsky, Olya; Krystal, Andrew D.; Shapiro, Colin M.

2017-01-01

Abstract Study Objective: To compare cognitive behavioral therapy for insomnia (CBT-I) + antidepressant medication (AD) against treatments that target solely depression or solely insomnia. Design: A blinded, randomized split-plot experimental study. Setting: Two urban academic clinical centers. Participants: 107 participants (68% female, mean age 42 ± 11) with major depressive disorder and insomnia. Interventions: Randomization was to one of three groups: antidepressant (AD; escitalopram) + CBT-I (4 sessions), CBT-I + placebo pill, or AD + 4-session sleep hygiene control (SH). Measurements and Results: Subjective sleep was assessed via 2 weeks of daily sleep diaries (use of medication was covaried in all analyses); although there were no statistically significant group differences detected, all groups improved from baseline to posttreatment on subjective sleep efficiency (SE) and total wake time (TWT) and the effect sizes were large. Objective sleep was assessed via overnight polysomnographic monitoring at baseline and posttreatment; analyses revealed both CBT groups improved on TWT (p = .03), but the AD + SH group worsened. There was no statistically significant effect for PSG SE (p = .07). There was a between groups medium effect observed for the AD + SH and CBT + placebo group differences on diary TWT and both PSG variables. All groups improved significantly from baseline to posttreatment on the Hamilton Rating Scale for Depression (HAMD-17); the groups did not differ. Conclusions: Although all groups self-reported sleeping better after treatment, only the CBT-I groups improved on objective sleep, and AD + SH’s sleep worsened. This suggests that we should be treating sleep in those with depression with an effective insomnia treatment and relying on self-report obscures sleep worsening effects. All groups improved on depression, even a group with absolutely no depression-focused treatment component (CBT-I + placebo). The depression effect in CBT-I only group has been reported in other studies, suggesting that we should further investigate the antidepressant properties of CBT-I. PMID:28199710

A comprehensive neuropsychological mapping battery for functional magnetic resonance imaging.

PubMed

Karakas, Sirel; Baran, Zeynel; Ceylan, Arzu Ozkan; Tileylioglu, Emre; Tali, Turgut; Karakas, Hakki Muammer

2013-11-01

Existing batteries for FMRI do not precisely meet the criteria for comprehensive mapping of cognitive functions within minimum data acquisition times using standard scanners and head coils. The goal was to develop a battery of neuropsychological paradigms for FMRI that can also be used in other brain imaging techniques and behavioural research. Participants were 61 healthy, young adult volunteers (48 females and 13 males, mean age: 22.25 ± 3.39 years) from the university community. The battery included 8 paradigms for basic (visual, auditory, sensory-motor, emotional arousal) and complex (language, working memory, inhibition/interference control, learning) cognitive functions. Imaging was performed using standard functional imaging capabilities (1.5-T MR scanner, standard head coil). Structural and functional data series were analysed using Brain Voyager QX2.9 and Statistical Parametric Mapping-8. For basic processes, activation centres for individuals were within a distance of 3-11 mm of the group centres of the target regions and for complex cognitive processes, between 7 mm and 15 mm. Based on fixed-effect and random-effects analyses, the distance between the activation centres was 0-4 mm. There was spatial variability between individual cases; however, as shown by the distances between the centres found with fixed-effect and random-effects analyses, the coordinates for individual cases can be used to represent those of the group. The findings show that the neuropsychological brain mapping battery described here can be used in basic science studies that investigate the relationship of the brain to the mind and also as functional localiser in clinical studies for diagnosis, follow-up and pre-surgical mapping. © 2013.

Long-Term Efficacy of Maintenance Therapy for Multiple Myeloma: A Quantitative Synthesis of 22 Randomized Controlled Trials.

PubMed

Li, Jie-Li; Fan, Guang-Yu; Liu, Yu-Jie; Zeng, Zi-Hang; Huang, Jing-Juan; Yang, Zong-Ming; Meng, Xiang-Yu

2018-01-01

We aimed to quantitatively synthesize data from randomized controlled trials (RCTs) concerning maintenance for multiple myeloma (MM). We searched electronic literature databases and conference proceedings to identify relevant RCTs. We selected eligible RCTs using predefined selection criteria. We conducted meta-analysis comparing maintenance containing new agents and conventional maintenance, and subgroup analysis by transplantation status and mainstay agent as well. We performed trial sequential analysis (TSA) to determine adequacy of sample size for overall and subgroup meta-analyses. We performed network meta-analysis (NMA) to compare and rank included regimens. A total of 22 RCTs involving 9,968 MM patients and 15 regimens were included, the overall quality of which was adequate. Significant heterogeneity was detected for progression-free survival (PFS) but not overall survival (OS). Meta-analyses showed that maintenance containing new agents significantly improved PFS but not OS [PFS: Hazard Ratio (HR) = 0.59, 95% Confidence Interval (CI) = 0.54 to 0.64; OS: HR = 0.93, 95% CI = 0.87 to 1.00], compared with controls. Subgroup analyses revealed lenalidomide (Len)-based therapies better than thalidomide-based ones (HR = 0.50 and 0.66, respectively; P = 0.001). NMA revealed that most of the maintenance regimens containing new agents were significantly better than simple observation in terms of PFS but not OS. Len single agent was the most effective, considering PFS and OS both. We concluded that conventional maintenance has very limited effect. Maintenance containing new agents is highly effective in improving PFS, but has very limited effect on OS. Maintenance with Len may have the largest survival benefits. Emerging strategies may further change the landscape of maintenance of MM.

Optimal patient education for cancer pain: a systematic review and theory-based meta-analysis.

PubMed

Marie, N; Luckett, T; Davidson, P M; Lovell, M; Lal, S

2013-12-01

Previous systematic reviews have found patient education to be moderately efficacious in decreasing the intensity of cancer pain, but variation in results warrants analysis aimed at identifying which strategies are optimal. A systematic review and meta-analysis was undertaken using a theory-based approach to classifying and comparing educational interventions for cancer pain. The reference lists of previous reviews and MEDLINE, PsycINFO, and CENTRAL were searched in May 2012. Studies had to be published in a peer-reviewed English language journal and compare the effect on cancer pain intensity of education with usual care. Meta-analyses used standardized effect sizes (ES) and a random effects model. Subgroup analyses compared intervention components categorized using the Michie et al. (Implement Sci 6:42, 2011) capability, opportunity, and motivation behavior (COM-B) model. Fifteen randomized controlled trials met the criteria. As expected, meta-analysis identified a small-moderate ES favoring education versus usual care (ES, 0.27 [-0.47, -0.07]; P = 0.007) with substantial heterogeneity (I² = 71 %). Subgroup analyses based on the taxonomy found that interventions using "enablement" were efficacious (ES, 0.35 [-0.63, -0.08]; P = 0.01), whereas those lacking this component were not (ES, 0.18 [-0.46, 0.10]; P = 0.20). However, the subgroup effect was nonsignificant (P = 0.39), and heterogeneity was not reduced. Factoring in the variable of individualized versus non-individualized influenced neither efficacy nor heterogeneity. The current meta-analysis follows a trend in using theory to understand the mechanisms of complex interventions. We suggest that future efforts focus on interventions that target patient self-efficacy. Authors are encouraged to report comprehensive details of interventions and methods to inform synthesis, replication, and refinement.

Power considerations for λ inflation factor in meta-analyses of genome-wide association studies.

PubMed

Georgiopoulos, Georgios; Evangelou, Evangelos

2016-05-19

The genomic control (GC) approach is extensively used to effectively control false positive signals due to population stratification in genome-wide association studies (GWAS). However, GC affects the statistical power of GWAS. The loss of power depends on the magnitude of the inflation factor (λ) that is used for GC. We simulated meta-analyses of different GWAS. Minor allele frequency (MAF) ranged from 0·001 to 0·5 and λ was sampled from two scenarios: (i) random scenario (empirically-derived distribution of real λ values) and (ii) selected scenario from simulation parameter modification. Adjustment for λ was considered under single correction (within study corrected standard errors) and double correction (additional λ corrected summary estimate). MAF was a pivotal determinant of observed power. In random λ scenario, double correction induced a symmetric power reduction in comparison to single correction. For MAF 1·2 and MAF >5%. Our results provide a quick but detailed index for power considerations of future meta-analyses of GWAS that enables a more flexible design from early steps based on the number of studies accumulated in different groups and the λ values observed in the single studies.

Meta-analysis of randomized clinical trials in the era of individual patient data sharing.

PubMed

Kawahara, Takuya; Fukuda, Musashi; Oba, Koji; Sakamoto, Junichi; Buyse, Marc

2018-06-01

Individual patient data (IPD) meta-analysis is considered to be a gold standard when the results of several randomized trials are combined. Recent initiatives on sharing IPD from clinical trials offer unprecedented opportunities for using such data in IPD meta-analyses. First, we discuss the evidence generated and the benefits obtained by a long-established prospective IPD meta-analysis in early breast cancer. Next, we discuss a data-sharing system that has been adopted by several pharmaceutical sponsors. We review a number of retrospective IPD meta-analyses that have already been proposed using this data-sharing system. Finally, we discuss the role of data sharing in IPD meta-analysis in the future. Treatment effects can be more reliably estimated in both types of IPD meta-analyses than with summary statistics extracted from published papers. Specifically, with rich covariate information available on each patient, prognostic and predictive factors can be identified or confirmed. Also, when several endpoints are available, surrogate endpoints can be assessed statistically. Although there are difficulties in conducting, analyzing, and interpreting retrospective IPD meta-analysis utilizing the currently available data-sharing systems, data sharing will play an important role in IPD meta-analysis in the future.

A Bayesian, generalized frailty model for comet assays.

PubMed

Ghebretinsae, Aklilu Habteab; Faes, Christel; Molenberghs, Geert; De Boeck, Marlies; Geys, Helena

2013-05-01

This paper proposes a flexible modeling approach for so-called comet assay data regularly encountered in preclinical research. While such data consist of non-Gaussian outcomes in a multilevel hierarchical structure, traditional analyses typically completely or partly ignore this hierarchical nature by summarizing measurements within a cluster. Non-Gaussian outcomes are often modeled using exponential family models. This is true not only for binary and count data, but also for, example, time-to-event outcomes. Two important reasons for extending this family are for (1) the possible occurrence of overdispersion, meaning that the variability in the data may not be adequately described by the models, which often exhibit a prescribed mean-variance link, and (2) the accommodation of a hierarchical structure in the data, owing to clustering in the data. The first issue is dealt with through so-called overdispersion models. Clustering is often accommodated through the inclusion of random subject-specific effects. Though not always, one conventionally assumes such random effects to be normally distributed. In the case of time-to-event data, one encounters, for example, the gamma frailty model (Duchateau and Janssen, 2007 ). While both of these issues may occur simultaneously, models combining both are uncommon. Molenberghs et al. ( 2010 ) proposed a broad class of generalized linear models accommodating overdispersion and clustering through two separate sets of random effects. Here, we use this method to model data from a comet assay with a three-level hierarchical structure. Although a conjugate gamma random effect is used for the overdispersion random effect, both gamma and normal random effects are considered for the hierarchical random effect. Apart from model formulation, we place emphasis on Bayesian estimation. Our proposed method has an upper hand over the traditional analysis in that it (1) uses the appropriate distribution stipulated in the literature; (2) deals with the complete hierarchical nature; and (3) uses all information instead of summary measures. The fit of the model to the comet assay is compared against the background of more conventional model fits. Results indicate the toxicity of 1,2-dimethylhydrazine dihydrochloride at different dose levels (low, medium, and high).

Placebo and nocebo reactions in randomized trials of pharmacological treatments for persistent depressive disorder. A meta-regression analysis.

PubMed

Meister, Ramona; Jansen, Alessa; Härter, Martin; Nestoriuc, Yvonne; Kriston, Levente

2017-06-01

We aimed to investigate placebo and nocebo reactions in randomized controlled trials (RCT) of pharmacological treatments for persistent depressive disorder (PDD). We conducted a systematic electronic search and included RCTs investigating antidepressants for the treatment of PDD. Outcomes were the number of patients experiencing response and remission in placebo arms (=placebo reaction). Additional outcomes were the incidence of patients experiencing adverse events and related discontinuations in placebo arms (=nocebo reaction). A priori defined effect modifiers were analyzed using a series of meta-regression analyses. Twenty-three trials were included in the analyses. We found a pooled placebo response rate of 31% and a placebo remission rate of 22%. The pooled adverse event rate and related discontinuations were 57% and 4%, respectively. All placebo arm outcomes were positively associated with the corresponding medication arm outcomes. Placebo response rate was associated with a greater proportion of patients with early onset depression, a smaller chance to receive placebo and a larger sample size. The adverse event rate in placebo arms was associated with a greater proportion of patients with early onset depression, a smaller proportion of females and a more recent publication. Pooled placebo and nocebo reaction rates in PDD were comparable to those in episodic depression. The identified effect modifiers should be considered to assess unbiased effects in RCTs, to influence placebo and nocebo reactions in practice. Limitations result from the methodology applied, the fact that we conducted only univariate analyses, and the number and quality of included trials. Copyright © 2017 Elsevier B.V. All rights reserved.

Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses

PubMed Central

Khankari, Nikhil K.; Shu, Xiao-Ou; Wen, Wanqing; Kraft, Peter; Lindström, Sara; Peters, Ulrike; Schildkraut, Joellen; Schumacher, Fredrick; Bofetta, Paolo; Risch, Angela; Bickeböller, Heike; Amos, Christopher I.; Easton, Douglas; Gruber, Stephen B.; Haiman, Christopher A.; Hunter, David J.; Chanock, Stephen J.; Pierce, Brandon L.; Zheng, Wei

2016-01-01

Background Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using height-associated genetic variants identified in a genome-wide association study (GWAS), to evaluate the association of adult height with these cancers. Methods and Findings A systematic review of prospective studies was conducted using the PubMed, Embase, and Web of Science databases. Using meta-analyses, results obtained from 62 studies were summarized for the association of a 10-cm increase in height with cancer risk. Mendelian randomization analyses were conducted using summary statistics obtained for 423 genetic variants identified from a recent GWAS of adult height and from a cancer genetics consortium study of multiple cancers that included 47,800 cases and 81,353 controls. For a 10-cm increase in height, the summary relative risks derived from the meta-analyses of prospective studies were 1.12 (95% CI 1.10, 1.15), 1.07 (95% CI 1.05, 1.10), and 1.06 (95% CI 1.02, 1.11) for colorectal, prostate, and lung cancers, respectively. Mendelian randomization analyses showed increased risks of colorectal (odds ratio [OR] = 1.58, 95% CI 1.14, 2.18) and lung cancer (OR = 1.10, 95% CI 1.00, 1.22) associated with each 10-cm increase in genetically predicted height. No association was observed for prostate cancer (OR = 1.03, 95% CI 0.92, 1.15). Our meta-analysis was limited to published studies. The sample size for the Mendelian randomization analysis of colorectal cancer was relatively small, thus affecting the precision of the point estimate. Conclusions Our study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the risk of these cancers. PMID:27598322

The Effect of IV Amino Acid Supplementation on Mortality in ICU Patients May Be Dependent on Kidney Function: Post Hoc Subgroup Analyses of a Multicenter Randomized Trial.

PubMed

Zhu, Ran; Allingstrup, Matilde J; Perner, Anders; Doig, Gordon S

2018-05-15

We investigated whether preexisting kidney function determines if ICU patients may benefit from increased (2.0 g/kg/d) protein intake. Post hoc, hypothesis-generating, subgroup analysis of a multicenter, phase 2, randomized clinical trial. All analyses were conducted by intention to treat and maintained group allocation. Ninety-day mortality was the primary outcome. ICUs of 16 hospitals throughout Australia and New Zealand. Adult critically ill patients expected to remain in the study ICU for longer than 2 days. Random allocation to receive a daily supplement of up to 100 g of IV amino acids to achieve a total protein intake of 2.0 g/kg/d or standard nutrition care. A total of 474 patients were randomized: 235 to standard care and 239 to IV amino acid supplementation. There was a statistically significant interaction between baseline kidney function and supplementation with study amino acids (p value for interaction = 0.026). Within the subgroup of patients with normal kidney function at randomization, patients who were allocated to receive the study amino acid supplement were less likely to die before study day 90 (covariate-adjusted risk difference, -7.9%; 95% CI, -15.1 to -0.7; p = 0.034). Furthermore, amino acid supplementation significantly increased estimated glomerular filtration rate in these patients (repeated-measures treatment × time interaction p = 0.009). Within the subgroup of patients with baseline kidney dysfunction and/or risk of progression of acute kidney injury, a significant effect of the study intervention on mortality was not found (covariate-adjusted risk difference, -0.6%; 95% CI, -16.2 to 15.2; p = 0.95). In this post hoc, hypothesis-generating, subgroup analysis, we observed reduced mortality and improved estimated glomerular filtration rate in ICU patients with normal kidney function who were randomly allocated to receive increased protein intake (up to 2.0 g/kg/d). We strongly recommend confirmation of these results in trials with low risk of bias before this treatment is recommended for routine care.

The Traditional Chinese Medicine and Relevant Treatment for the Efficacy and Safety of Atopic Dermatitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Shi, Zhao-feng; Song, Tie-bing; Xie, Juan; Yan, Yi-quan

2017-01-01

Background Atopic dermatitis (AD) has become a common skin disease that requires systematic and comprehensive treatment to achieve adequate clinical control. Traditional Chinese medicines and related treatments have shown clinical effects for AD in many studies. But the systematic reviews and meta-analyses for them are lacking. Objective The systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement were conducted to evaluate the efficacy and safety of traditional Chinese medicines and related treatments for AD treatment. Methods Randomized controlled trials (RCTs) were searched based on standardized searching rules in eight medical databases from the inception up to December 2016 and a total of 24 articles with 1,618 patients were enrolled in this meta-analysis. Results The results revealed that traditional Chinese medicines and related treatments did not show statistical differences in clinical effectiveness, SCORAD amelioration, and SSRI amelioration for AD treatment compared with control group. However, EASI amelioration of traditional Chinese medicines and related treatments for AD was superior to control group. Conclusion We need to make conclusion cautiously for the efficacy and safety of traditional Chinese medicine and related treatment on AD therapy. More standard, multicenter, double-blind randomized controlled trials (RCTs) of traditional Chinese medicine and related treatment for AD were required to be conducted for more clinical evidences providing in the future. PMID:28713436

Attention Restoration Theory: A systematic review of the attention restoration potential of exposure to natural environments.

PubMed

Ohly, Heather; White, Mathew P; Wheeler, Benedict W; Bethel, Alison; Ukoumunne, Obioha C; Nikolaou, Vasilis; Garside, Ruth

2016-01-01

Attention Restoration Theory (ART) suggests the ability to concentrate may be restored by exposure to natural environments. Although widely cited, it is unclear as to the quantity of empirical evidence that supports this. A systematic review regarding the impact of exposure to natural environments on attention was conducted. Seven electronic databases were searched. Studies were included if (1) they were natural experiments, randomized investigations, or recorded "before and after" measurements; (2) compared natural and nonnatural/other settings; and (3) used objective measures of attention. Screening of articles for inclusion, data extraction, and quality appraisal were performed by one reviewer and checked by another. Where possible, random effects meta-analysis was used to pool effect sizes. Thirty-one studies were included. Meta-analyses provided some support for ART, with significant positive effects of exposure to natural environments for three measures (Digit Span Forward, Digit Span Backward, and Trail Making Test B). The remaining 10 meta-analyses did not show marked beneficial effects. Meta-analysis was limited by small numbers of investigations, small samples, heterogeneity in reporting of study quality indicators, and heterogeneity of outcomes. This review highlights the diversity of evidence around ART in terms of populations, study design, and outcomes. There is uncertainty regarding which aspects of attention may be affected by exposure to natural environments.

Short communication: Principal components and factor analytic models for test-day milk yield in Brazilian Holstein cattle.

PubMed

Bignardi, A B; El Faro, L; Rosa, G J M; Cardoso, V L; Machado, P F; Albuquerque, L G

2012-04-01

A total of 46,089 individual monthly test-day (TD) milk yields (10 test-days), from 7,331 complete first lactations of Holstein cattle were analyzed. A standard multivariate analysis (MV), reduced rank analyses fitting the first 2, 3, and 4 genetic principal components (PC2, PC3, PC4), and analyses that fitted a factor analytic structure considering 2, 3, and 4 factors (FAS2, FAS3, FAS4), were carried out. The models included the random animal genetic effect and fixed effects of the contemporary groups (herd-year-month of test-day), age of cow (linear and quadratic effects), and days in milk (linear effect). The residual covariance matrix was assumed to have full rank. Moreover, 2 random regression models were applied. Variance components were estimated by restricted maximum likelihood method. The heritability estimates ranged from 0.11 to 0.24. The genetic correlation estimates between TD obtained with the PC2 model were higher than those obtained with the MV model, especially on adjacent test-days at the end of lactation close to unity. The results indicate that for the data considered in this study, only 2 principal components are required to summarize the bulk of genetic variation among the 10 traits. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Logistic random effects regression models: a comparison of statistical packages for binary and ordinal outcomes

PubMed Central

2011-01-01

Background Logistic random effects models are a popular tool to analyze multilevel also called hierarchical data with a binary or ordinal outcome. Here, we aim to compare different statistical software implementations of these models. Methods We used individual patient data from 8509 patients in 231 centers with moderate and severe Traumatic Brain Injury (TBI) enrolled in eight Randomized Controlled Trials (RCTs) and three observational studies. We fitted logistic random effects regression models with the 5-point Glasgow Outcome Scale (GOS) as outcome, both dichotomized as well as ordinal, with center and/or trial as random effects, and as covariates age, motor score, pupil reactivity or trial. We then compared the implementations of frequentist and Bayesian methods to estimate the fixed and random effects. Frequentist approaches included R (lme4), Stata (GLLAMM), SAS (GLIMMIX and NLMIXED), MLwiN ([R]IGLS) and MIXOR, Bayesian approaches included WinBUGS, MLwiN (MCMC), R package MCMCglmm and SAS experimental procedure MCMC. Three data sets (the full data set and two sub-datasets) were analysed using basically two logistic random effects models with either one random effect for the center or two random effects for center and trial. For the ordinal outcome in the full data set also a proportional odds model with a random center effect was fitted. Results The packages gave similar parameter estimates for both the fixed and random effects and for the binary (and ordinal) models for the main study and when based on a relatively large number of level-1 (patient level) data compared to the number of level-2 (hospital level) data. However, when based on relatively sparse data set, i.e. when the numbers of level-1 and level-2 data units were about the same, the frequentist and Bayesian approaches showed somewhat different results. The software implementations differ considerably in flexibility, computation time, and usability. There are also differences in the availability of additional tools for model evaluation, such as diagnostic plots. The experimental SAS (version 9.2) procedure MCMC appeared to be inefficient. Conclusions On relatively large data sets, the different software implementations of logistic random effects regression models produced similar results. Thus, for a large data set there seems to be no explicit preference (of course if there is no preference from a philosophical point of view) for either a frequentist or Bayesian approach (if based on vague priors). The choice for a particular implementation may largely depend on the desired flexibility, and the usability of the package. For small data sets the random effects variances are difficult to estimate. In the frequentist approaches the MLE of this variance was often estimated zero with a standard error that is either zero or could not be determined, while for Bayesian methods the estimates could depend on the chosen "non-informative" prior of the variance parameter. The starting value for the variance parameter may be also critical for the convergence of the Markov chain. PMID:21605357

Specifying a target trial prevents immortal time bias and other self-inflicted injuries in observational analyses.

PubMed

Hernán, Miguel A; Sauer, Brian C; Hernández-Díaz, Sonia; Platt, Robert; Shrier, Ian

2016-11-01

Many analyses of observational data are attempts to emulate a target trial. The emulation of the target trial may fail when researchers deviate from simple principles that guide the design and analysis of randomized experiments. We review a framework to describe and prevent biases, including immortal time bias, that result from a failure to align start of follow-up, specification of eligibility, and treatment assignment. We review some analytic approaches to avoid these problems in comparative effectiveness or safety research. Copyright © 2016 Elsevier Inc. All rights reserved.

Efficacy and Safety of Vasopressin Receptor Antagonists for Euvolemic or Hypervolemic Hyponatremia: A Meta-Analysis.

PubMed

Zhang, Xiangyun; Zhao, Mingyi; Du, Wei; Zu, Dongni; Sun, Yingwei; Xiang, Rongwu; Yang, Jingyu

2016-04-01

Hyponatremia, defined as a nonartifactual serum sodium level <135 mmol/L, is the most common fluid and electrolyte abnormality in clinical practice. Traditional managements (fluid restriction, hypertonic saline and loop diuretics, etc.) are difficult to maintain or ineffective. Recently, vasopressin receptor antagonists (VRAs) have shown promise for the treatment of hyponatremia. We aimed to conduct a meta-analysis to evaluate the efficacy and safety of VRAs in patients with euvolemic or hypervolemic hyponatremia. We searched Pubmed, Cochrane Library, Web of Science and Springer, etc. (latest search on June 4, 2015) for English publications with randomized controlled trials. Two authors independently screened the citations and extracted data. We calculated pooled relative risk (RR), risk difference (RD), weighted mean difference (WMD) or standard mean difference (SMD), and 95% confidence intervals (CIs) by using random and fixed effect models. We collected data from 18 trials involving 1806 patients. Both random and fixed effect meta-analyses showed that VRAs significantly increased the net change of serum sodium concentration (WMD(random) = 4.89 mEq/L, 95%CIs = 4.35-5.43 and WMD(fixed) = 4.70 mEq/L, 95%CIs = 4.45-4.95), response rate (RR(random )= 2.77, 95%CIs = 2.29-3.36 and RR(fixed) = 2.95, 95%CIs = 2.56-3.41), and 24-hour urine output (SMD(random) = 0.82, 95%CIs = 0.65-1.00 and SMD(fixed) = 0.79, 95%CIs = 0.66-0.93) compared to placebo. Furthermore, VRAs significantly decreased body weight (WMD(random) = -0.87 kg, 95%CIs = -1.24 to -0.49 and WMD(fixed) = -0.91 kg, 95%CIs = -1.22 to -0.59). In terms of safety, rates of drug-related adverse events (AEs), rapid sodium level correction, constipation, dry mouth, thirst, and phlebitis in the VRA-treated group were greater than those in control group. However, there was no difference in the total number of AEs, discontinuations due to AEs, serious AEs, death, headache, hypotension, nausea, anemia, hypernatremia, urinary tract infection, renal failure, pyrexia, upper gastrointestinal bleeding, diarrhea, vomiting, peripheral edema, and dizziness between the 2 groups. Random effect meta-analyses showed that post treatment urine osmolality, supine systolic blood pressure, and diastolic blood pressure were lowered (WMD(random) = -233.07 mOsmol/kg, 95%CIs = -298.20-147.94; WMD(random) = -6.11 mmHg, 95%CIs = -9.810 to -2.41; WMD(random )= -2.59 mmHg, 95%CIs = -4.06 to -1.11, respectively), but serum osmolality was increased (WMD(random) = 9.29 mOsmol/kg, 95%CIs = 5.56-13.03). There was no significant change from baseline in serum potassium concentration between the 2 groups (WMD(fixed) = 0.00 mmHg, 95%CIs = -0.07-0.06). VRAs are relatively effective and safe for the treatment of hypervolemic and euvolemic hyponatremia.

Effects of AlcoholEdu for College on Alcohol-Related Problems Among Freshmen: A Randomized Multicampus Trial*

PubMed Central

Paschall, Mallie J.; Antin, Tamar; Ringwalt, Christopher L.; Saltz, Robert F.

2011-01-01

Objective: AlcoholEdu for College is a 2- to 3-hour online course for incoming college freshmen. This study was the first multicampus trial to examine effects of AlcoholEdu for College on alcohol-related problems among freshmen. Method: Thirty universi participated in the study. Fifteen were randomly assigned to receive AlcoholEdu, and the other 15 were assigned to the control condition. AlcoholEdu was implemented by intervention schools during the summer and/or fall semester. Cross-sectional surveys of freshmen were conducted at each university beginning before the intervention in spring 2008/2009; post-intervention surveys were administered in fall 2008/2009 and spring 2009/2010. The surveys included questions about the past-30-day frequency of 28 alcohol-related problems, from which we created indices for the total number of problems and problems in seven domains: physiological, academic, social, driving under the influence/riding with drinking drivers, aggression, sexual risk taking, and victimization. Multilevel Poisson regression analyses were conducted to examine intent-to-treat and dosage effects of AlcoholEdu for College on these outcomes. Results: Multilevel intent-to-treat analyses indicated significant reductions in the risk for past-30-day alcohol problems in general and problems in the physiological, social, and victimization domains during the fall semester immediately after completion of the course. However, these effects did not persist in the spring semester. Additional analyses suggested stronger AlcoholEdu effects on these outcomes at colleges with higher rates of student course completion. No AlcoholEdu effects were observed for alcohol-related problems in the other four domains. Conclusions: AlcoholEdu for College appears to have beneficial short-term effects on victimization and the most common types of alcohol-related problems among freshmen. Universities may benefit the most by mandating AlcoholEdu for College for all incoming freshmen and by implementing this online course along with environmental prevention strategies. PMID:21683046

Differential change in integrative psychotherapy: a re-analysis of a change-factor based RCT in a naturalistic setting.

PubMed

Holtforth, Martin Grosse; Wilm, Katharina; Beyermann, Stefanie; Rhode, Annemarie; Trost, Stephanie; Steyer, Rolf

2011-11-01

General Psychotherapy (GPT; Grawe, 1997) is a research-informed psychotherapy that combines cognitive-behavioral and process-experiential techniques and that assumes motivational clarification and problem mastery as central mechanisms of change. To isolate the effect of motivational clarification, GPT was compared to a treatment that proscribed motivational clarification (General Psychotherapy Minus Clarification, GPT-C) in a randomized-controlled trial with 67 diagnostically heterogeneous outpatients. Previous analyses demonstrated equal outcomes and some superiority for highly avoidant patients in GPT. Re-analyses using causal-analytic methods confirmed equal changes, but also showed superior effects for GPT in highly symptomatic patients. Results are discussed regarding theory, methodological limitations, and implications for research and practice.

No improvement in the reporting of clinical trial subgroup effects in high-impact general medical journals.

PubMed

Gabler, Nicole B; Duan, Naihua; Raneses, Eli; Suttner, Leah; Ciarametaro, Michael; Cooney, Elizabeth; Dubois, Robert W; Halpern, Scott D; Kravitz, Richard L

2016-07-16

When subgroup analyses are not correctly analyzed and reported, incorrect conclusions may be drawn, and inappropriate treatments provided. Despite the increased recognition of the importance of subgroup analysis, little information exists regarding the prevalence, appropriateness, and study characteristics that influence subgroup analysis. The objective of this study is to determine (1) if the use of subgroup analyses and multivariable risk indices has increased, (2) whether statistical methodology has improved over time, and (3) which study characteristics predict subgroup analysis. We randomly selected randomized controlled trials (RCTs) from five high-impact general medical journals during three time periods. Data from these articles were abstracted in duplicate using standard forms and a standard protocol. Subgroup analysis was defined as reporting any subgroup effect. Appropriate methods for subgroup analysis included a formal test for heterogeneity or interaction across treatment-by-covariate groups. We used logistic regression to determine the variables significantly associated with any subgroup analysis or, among RCTs reporting subgroup analyses, using appropriate methodology. The final sample of 416 articles reported 437 RCTs, of which 270 (62 %) reported subgroup analysis. Among these, 185 (69 %) used appropriate methods to conduct such analyses. Subgroup analysis was reported in 62, 55, and 67 % of the articles from 2007, 2010, and 2013, respectively. The percentage using appropriate methods decreased over the three time points from 77 % in 2007 to 63 % in 2013 (p < 0.05). Significant predictors of reporting subgroup analysis included industry funding (OR 1.94 (95 % CI 1.17, 3.21)), sample size (OR 1.98 per quintile (1.64, 2.40), and a significant primary outcome (OR 0.55 (0.33, 0.92)). The use of appropriate methods to conduct subgroup analysis decreased by year (OR 0.88 (0.76, 1.00)) and was less common with industry funding (OR 0.35 (0.18, 0.70)). Only 33 (18 %) of the RCTs examined subgroup effects using a multivariable risk index. While we found no significant increase in the reporting of subgroup analysis over time, our results show a significant decrease in the reporting of subgroup analyses using appropriate methods during recent years. Industry-sponsored trials may more commonly report subgroup analyses, but without utilizing appropriate methods. Suboptimal reporting of subgroup effects may impact optimal physician-patient decision-making.

Effects of omega-3 fatty acid supplementation on mood and emotional information processing in recovered depressed individuals.

PubMed

Antypa, Niki; Smelt, August H M; Strengholt, Annette; Van der Does, A J Willem

2012-05-01

Beneficial effects of omega-3 fatty acids have been reported for several psychiatric disorders, particularly for depression. Association studies show a relationship between omega-3 intake and depression risk. Meta-analyses of clinical trials have shown a moderate effect of supplementation on depressive symptoms, but not on normal mood states. Few studies have investigated effects on cognition. The purpose of this study was to examine effects of omega-3 supplements on cognition and mood of recovered depressed individuals. Seventy-one participants were randomized to receive either omega-3 or placebo for four weeks in a randomized double-blind design. Results showed small effects of omega-3 supplementation on aspects of emotional decision-making and on self-reported states of depression and tension. Some of the effects were confounded by learning effects. No significant effects were observed on memory, attention, cognitive reactivity and depressive symptoms. While inconclusive, the present findings may indicate that omega-3 supplementation has selective effects on emotional cognition and mood in recovered depressed participants.

Within-Tunnel Variations in Pressure Data for Three Transonic Wind Tunnels

NASA Technical Reports Server (NTRS)

DeLoach, Richard

2014-01-01

This paper compares the results of pressure measurements made on the same test article with the same test matrix in three transonic wind tunnels. A comparison is presented of the unexplained variance associated with polar replicates acquired in each tunnel. The impact of a significance component of systematic (not random) unexplained variance is reviewed, and the results of analyses of variance are presented to assess the degree of significant systematic error in these representative wind tunnel tests. Total uncertainty estimates are reported for 140 samples of pressure data, quantifying the effects of within-polar random errors and between-polar systematic bias errors.

The Current Indication for Pacemaker in Patients with Cardioinhibitory Vasovagal Syncope

PubMed Central

da Silva, Rose Mary Ferreira Lisboa

2016-01-01

The most frequent cause of syncope is vasovagal reflex. It is associated with worse quality of life, depression, fatigue and physical injury. Recurrence of vasovagal syncope is an aggravating, reaching the rate of 69%. Initial step and pharmacological treatment may not work, especially in patients with recurrent syncope without prodrome. These patients can present cardioinhibitory response with asystole. Studies were designed to analyses the effectiveness of pacemaker for prevention of syncope. In this review, nonrandomized clinical trials, open-label randomized, double-blind randomized, placebo-controlled, and studies based on tilt test or Implantable Loop Recorder findings will be discussed. PMID:27651841

Differential Therapeutic Outcomes of Community-Based Group Interventions for Women and Children Exposed to Intimate Partner Violence

ERIC Educational Resources Information Center

McWhirter, Paula T.

2011-01-01

Two community-based group therapies, emotion focused versus goal oriented, are compared among women exposed to intimate partner violence (n = 46) and their children (n = 48) aged between 6 and 12 years. A series of repeated measures analyses are employed to evaluate the effects of time from baseline to postintervention following random assignment.…

Do Effects of Social-Emotional Learning Programs Vary by Level of Parent Participation? Evidence from a Randomized Trial

ERIC Educational Resources Information Center

McCormick, Meghan P.; Cappella, Elise; O'Connor, Erin E.; Hill, Jennifer; McClowry, Sandee G.

2016-01-01

A wide and rich body of literature has identified the family as the key context influencing children's development. In response, school districts and policymakers have sought to engage parents in children's learning, particularly low-income families. Meta-analyses conclude that efforts to engage low-income parents do improve students' academic…

Assessing the Accuracy of Classwide Direct Observation Methods: Two Analyses Using Simulated and Naturalistic Data

ERIC Educational Resources Information Center

Dart, Evan H.; Radley, Keith C.; Briesch, Amy M.; Furlow, Christopher M.; Cavell, Hannah J.; Briesch, Amy M.

2016-01-01

Two studies investigated the accuracy of eight different interval-based group observation methods that are commonly used to assess the effects of classwide interventions. In Study 1, a Microsoft Visual Basic program was created to simulate a large set of observational data. Binary data were randomly generated at the student level to represent…

Mental Health Promotion as a New Goal in Public Mental Health Care: A Randomized Controlled Trial of an Intervention Enhancing Psychological Flexibility

PubMed Central

Bohlmeijer, Ernst T.; Smit, Filip; Westerhof, Gerben J.

2010-01-01

Objectives. We assessed whether an intervention based on acceptance and commitment therapy (ACT) and mindfulness was successful in promoting positive mental health by enhancing psychological flexibility. Methods. Participants were 93 adults with mild to moderate psychological distress. They were randomly assigned to the group intervention (n = 49) or to a waiting-list control group (n = 44). Participants completed measures before and after the intervention as well as 3 months later at follow-up to assess mental health in terms of emotional, psychological, and social well-being (Mental Health Continuum–Short Form) as well as psychological flexibility (i.e., acceptance of present experiences and value-based behavior, Acceptance and Action Questionnaire-II). Results. Regression analyses showed that compared with the participants on the waiting list, participants in the ACT and mindfulness intervention had greater emotional and psychological well-being after the intervention and also greater psychological flexibility at follow-up. Mediational analyses showed that the enhancement of psychological flexibility during the intervention mediated the effects of the intervention on positive mental health. Conclusions. The intervention is effective in improving positive mental health by stimulating skills of acceptance and value-based action. PMID:20966360

Mental health promotion as a new goal in public mental health care: a randomized controlled trial of an intervention enhancing psychological flexibility.

PubMed

Fledderus, Martine; Bohlmeijer, Ernst T; Smit, Filip; Westerhof, Gerben J

2010-12-01

We assessed whether an intervention based on acceptance and commitment therapy (ACT) and mindfulness was successful in promoting positive mental health by enhancing psychological flexibility. Participants were 93 adults with mild to moderate psychological distress. They were randomly assigned to the group intervention (n = 49) or to a waiting-list control group (n = 44). Participants completed measures before and after the intervention as well as 3 months later at follow-up to assess mental health in terms of emotional, psychological, and social well-being (Mental Health Continuum-Short Form) as well as psychological flexibility (i.e., acceptance of present experiences and value-based behavior, Acceptance and Action Questionnaire-II). Regression analyses showed that compared with the participants on the waiting list, participants in the ACT and mindfulness intervention had greater emotional and psychological well-being after the intervention and also greater psychological flexibility at follow-up. Mediational analyses showed that the enhancement of psychological flexibility during the intervention mediated the effects of the intervention on positive mental health. The intervention is effective in improving positive mental health by stimulating skills of acceptance and value-based action.

A Case for Less Intensive Blood Pressure Control: It Matters to Achieve Target Blood Pressure Early and Sustained Below 140/90mmHg.

PubMed

Mariampillai, Julian E; Eskås, Per Anders; Heimark, Sondre; Kjeldsen, Sverre E; Narkiewicz, Krzysztof; Mancia, Giuseppe

Although high blood pressure (BP) is the leading risk factors for cardiovascular (CV) disease, the optimal BP treatment target in order to reduce CV risk is unclear in the aftermath of the SPRINT study. The aim of this review is to assess large, randomized, and controlled trials on BP targets, as well as review selected observational analyses from other large randomized BP trials in order to evaluate the benefit of intense vs. standard BP control. None of the studies, except SPRINT, favored intense BP treatment. Some of the studies suggested favorable effects of lowering treatment target in patients with diabetes or high risk of stroke. In SPRINT, a new BP measurement method was introduced, and the results must be interpreted in light of this. The results of the observational analyses indicated the best preventive effect when achieving early and sustained BP control rather than low targets. In conclusion, today's guidelines' recommended treatment target of <140/90mmHg seems sufficient for most patients. Early and sustained BP control should be the main focus. Copyright © 2016 Elsevier Inc. All rights reserved.

Preventing postpartum depression: A meta-analytic review

PubMed Central

Sockol, Laura E.; Epperson, C. Neill; Barber, Jacques P.

2014-01-01

This meta-analysis assessed the efficacy of a wide range of preventive interventions designed to reduce the severity of postpartum depressive symptoms or decrease the prevalence of postpartum depressive episodes. A systematic review identified 37 randomized or quasi-randomized controlled trials in which an intervention was compared to a control condition. Differences between treatment and control conditions in the level of depressive symptoms and prevalence of depressive episodes by 6 months postpartum were assessed in separate analyses. Depressive symptoms were significantly lower at post-treatment in intervention conditions, with an overall effect size in the small range after exclusion of outliers (Hedges' g = 0.18). There was a 27% reduction in the prevalence of depressive episodes in intervention conditions by 6 months postpartum after removal of outliers and correction for publication bias. Later timing of the postpartum assessment was associated with smaller differences between intervention and control conditions in both analyses. Among studies that assessed depressive symptoms using the EPDS, higher levels of depressive symptoms at pre-treatment were associated with smaller differences in depressive symptoms by 6 months postpartum. These findings suggest that interventions designed to prevent postpartum depression effectively reduce levels of postpartum depressive symptoms and decrease risk for postpartum depressive episodes. PMID:24211712

To Wait in Tier 1 or Intervene Immediately: A Randomized Experiment Examining First Grade Response to Intervention (RTI) in Reading.

PubMed

Al Otaiba, Stephanie; Connor, Carol M; Folsom, Jessica S; Wanzek, Jeanne; Greulich, Luana; Schatschneider, Christopher; Wagner, Richard K

2014-10-01

This randomized controlled experiment compared the efficacy of two Response to Intervention (RTI) models - Typical RTI and Dynamic RTI - and included 34 first-grade classrooms ( n = 522 students) across 10 socio-economically and culturally diverse schools. Typical RTI was designed to follow the two-stage RTI decision rules that wait to assess response to Tier 1 in many districts, whereas Dynamic RTI provided Tier 2 or Tier 3 interventions immediately according to students' initial screening results. Interventions were identical across conditions except for when intervention began. Reading assessments included letter-sound, word, and passage reading, and teacher-reported severity of reading difficulties. An intent-to-treat analysis using multi-level modeling indicated an overall effect favoring the Dynamic RTI condition ( d = .36); growth curve analyses demonstrated that students in Dynamic RTI showed an immediate score advantage, and effects accumulated across the year. Analyses of standard score outcomes confirmed that students in the Dynamic condition who received Tier 2 and Tier 3 ended the study with significantly higher reading performance than students in the Typical condition. Implications for RTI implementation practice and for future research are discussed.

To Wait in Tier 1 or Intervene Immediately: A Randomized Experiment Examining First Grade Response to Intervention (RTI) in Reading

PubMed Central

Al Otaiba, Stephanie; Connor, Carol M.; Folsom, Jessica S.; Wanzek, Jeanne; Greulich, Luana; Schatschneider, Christopher; Wagner, Richard K.

2014-01-01

This randomized controlled experiment compared the efficacy of two Response to Intervention (RTI) models – Typical RTI and Dynamic RTI - and included 34 first-grade classrooms (n = 522 students) across 10 socio-economically and culturally diverse schools. Typical RTI was designed to follow the two-stage RTI decision rules that wait to assess response to Tier 1 in many districts, whereas Dynamic RTI provided Tier 2 or Tier 3 interventions immediately according to students’ initial screening results. Interventions were identical across conditions except for when intervention began. Reading assessments included letter-sound, word, and passage reading, and teacher-reported severity of reading difficulties. An intent-to-treat analysis using multi-level modeling indicated an overall effect favoring the Dynamic RTI condition (d = .36); growth curve analyses demonstrated that students in Dynamic RTI showed an immediate score advantage, and effects accumulated across the year. Analyses of standard score outcomes confirmed that students in the Dynamic condition who received Tier 2 and Tier 3 ended the study with significantly higher reading performance than students in the Typical condition. Implications for RTI implementation practice and for future research are discussed. PMID:25530622

Effects of a Web-Based Tailored Multiple-Lifestyle Intervention for Adults: A Two-Year Randomized Controlled Trial Comparing Sequential and Simultaneous Delivery Modes

PubMed Central

Kremers, Stef PJ; Vandelanotte, Corneel; van Adrichem, Mathieu JG; Schneider, Francine; Candel, Math JJM; de Vries, Hein

2014-01-01

Background Web-based computer-tailored interventions for multiple health behaviors can have a significant public health impact. Yet, few randomized controlled trials have tested this assumption. Objective The objective of this paper was to test the effects of a sequential and simultaneous Web-based tailored intervention on multiple lifestyle behaviors. Methods A randomized controlled trial was conducted with 3 tailoring conditions (ie, sequential, simultaneous, and control conditions) in the Netherlands in 2009-2012. Follow-up measurements took place after 12 and 24 months. The intervention content was based on the I-Change model. In a health risk appraisal, all respondents (N=5055) received feedback on their lifestyle behaviors that indicated whether they complied with the Dutch guidelines for physical activity, vegetable consumption, fruit consumption, alcohol intake, and smoking. Participants in the sequential (n=1736) and simultaneous (n=1638) conditions received tailored motivational feedback to change unhealthy behaviors one at a time (sequential) or all at the same time (simultaneous). Mixed model analyses were performed as primary analyses; regression analyses were done as sensitivity analyses. An overall risk score was used as outcome measure, then effects on the 5 individual lifestyle behaviors were assessed and a process evaluation was performed regarding exposure to and appreciation of the intervention. Results Both tailoring strategies were associated with small self-reported behavioral changes. The sequential condition had the most significant effects compared to the control condition after 12 months (T1, effect size=0.28). After 24 months (T2), the simultaneous condition was most effective (effect size=0.18). All 5 individual lifestyle behaviors changed over time, but few effects differed significantly between the conditions. At both follow-ups, the sequential condition had significant changes in smoking abstinence compared to the simultaneous condition (T1 effect size=0.31; T2 effect size=0.41). The sequential condition was more effective in decreasing alcohol consumption than the control condition at 24 months (effect size=0.27). Change was predicted by the amount of exposure to the intervention (total visiting time: beta=–.06; P=.01; total number of visits: beta=–.11; P<.001). Both interventions were appreciated well by respondents without significant differences between conditions. Conclusions Although evidence was found for the effectiveness of both programs, no simple conclusive finding could be drawn about which intervention mode was more effective. The best kind of intervention may depend on the behavior that is targeted or on personal preferences and motivation. Further research is needed to identify moderators of intervention effectiveness. The results need to be interpreted in view of the high and selective dropout rates, multiple comparisons, and modest effect sizes. However, a large number of people were reached at low cost and behavioral change was achieved after 2 years. Trial Registration Nederlands Trial Register: NTR 2168; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2168 (Archived by WebCite at http://www.webcitation.org/6MbUqttYB). PMID:24472854

The Impact of Asking Intention or Self-Prediction Questions on Subsequent Behavior

PubMed Central

Wood, Chantelle; Conner, Mark; Miles, Eleanor; Sandberg, Tracy; Taylor, Natalie; Godin, Gaston; Sheeran, Paschal

2015-01-01

The current meta-analysis estimated the magnitude of the impact of asking intention and self-prediction questions on rates of subsequent behavior, and examined mediators and moderators of this question–behavior effect (QBE). Random-effects meta-analysis on 116 published tests of the effect indicated that intention/prediction questions have a small positive effect on behavior (d+ = 0.24). Little support was observed for attitude accessibility, cognitive dissonance, behavioral simulation, or processing fluency explanations of the QBE. Multivariate analyses indicated significant effects of social desirability of behavior/behavior domain (larger effects for more desirable and less risky behaviors), difficulty of behavior (larger effects for easy-to-perform behaviors), and sample type (larger effects among student samples). Although this review controls for co-occurrence of moderators in multivariate analyses, future primary research should systematically vary moderators in fully factorial designs. Further primary research is also needed to unravel the mechanisms underlying different variants of the QBE. PMID:26162771

Interventions for reducing fear of childbirth: A systematic review and meta-analysis of clinical trials.

PubMed

MoghaddamHosseini, Vahideh; Nazarzadeh, Milad; Jahanfar, Shayesteh

2017-11-07

Fear of childbirth is a problematic mental health issue during pregnancy. But, effective interventions to reduce this problem are not well understood. To examine effective interventions for reducing fear of childbirth. The Cochrane Central Register of Controlled Trials, PubMed, Embase and PsycINFO were searched since inception till September 2017 without any restriction. Randomised controlled trials and quasi-randomised controlled trials comparing interventions for treatment of fear of childbirth were included. The standardized mean differences were pooled using random and fixed effect models. The heterogeneity was determined using the Cochran's test and I 2 index and was further explored in meta-regression model and subgroup analyses. Ten studies inclusive of 3984 participants were included in the meta-analysis (2 quasi-randomized and 8 randomized clinical trials). Eight studies investigated education and two studies investigated hypnosis-based intervention. The pooled standardized mean differences of fear for the education intervention and hypnosis group in comparison with control group were -0.46 (95% CI -0.73 to -0.19) and -0.22 (95% CI -0.34 to -0.10), respectively. Both types of interventions were effective in reducing fear of childbirth; however our pooled results revealed that educational interventions may reduce fear with double the effect of hypnosis. Further large scale randomized clinical trials and individual patient data meta-analysis are warranted for assessing the association. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

Comparison of random regression test-day models for Polish Black and White cattle.

PubMed

Strabel, T; Szyda, J; Ptak, E; Jamrozik, J

2005-10-01

Test-day milk yields of first-lactation Black and White cows were used to select the model for routine genetic evaluation of dairy cattle in Poland. The population of Polish Black and White cows is characterized by small herd size, low level of production, and relatively early peak of lactation. Several random regression models for first-lactation milk yield were initially compared using the "percentage of squared bias" criterion and the correlations between true and predicted breeding values. Models with random herd-test-date effects, fixed age-season and herd-year curves, and random additive genetic and permanent environmental curves (Legendre polynomials of different orders were used for all regressions) were chosen for further studies. Additional comparisons included analyses of the residuals and shapes of variance curves in days in milk. The low production level and early peak of lactation of the breed required the use of Legendre polynomials of order 5 to describe age-season lactation curves. For the other curves, Legendre polynomials of order 3 satisfactorily described daily milk yield variation. Fitting third-order polynomials for the permanent environmental effect made it possible to adequately account for heterogeneous residual variance at different stages of lactation.

Mindfulness-based interventions for binge eating: a systematic review and meta-analysis.

PubMed

Godfrey, Kathryn M; Gallo, Linda C; Afari, Niloofar

2015-04-01

Mindfulness-based interventions are increasingly used to treat binge eating. The effects of these interventions have not been reviewed comprehensively. This systematic review and meta-analysis sought to summarize the literature on mindfulness-based interventions and determine their impact on binge eating behavior. PubMED, Web of Science, and PsycINFO were searched using keywords binge eating, overeating, objective bulimic episodes, acceptance and commitment therapy, dialectical behavior therapy, mindfulness, meditation, mindful eating. Of 151 records screened, 19 studies met inclusion criteria. Most studies showed effects of large magnitude. Results of random effects meta-analyses supported large or medium-large effects of these interventions on binge eating (within-group random effects mean Hedge's g = -1.12, 95 % CI -1.67, -0.80, k = 18; between-group mean Hedge's g = -0.70, 95 % CI -1.16, -0.24, k = 7). However, there was high statistical heterogeneity among the studies (within-group I(2) = 93 %; between-group I(2) = 90 %). Limitations and future research directions are discussed.

A Randomized Controlled Trial of Relationship Education in the U.S. Army: 2-Year Outcomes

PubMed Central

Stanley, Scott M.; Rhoades, Galena K.; Loew, Benjamin A.; Allen, Elizabeth S.; Carter, Sarah; Osborne, Laura J.; Prentice, Donnella; Markman, Howard J.

2014-01-01

This study examined the effectiveness of an evidence-based, community-delivered adaptation of couple relationship education (CRE; specifically, PREP, The Prevention and Relationship Enhancement Program) delivered at two Army installations. The study is a randomized controlled trial with two years of follow-up, examining marital quality and stability. Sample composition was 662 married couples with a spouse in the U.S. Army. Analyses yielded no evidence of overall enduring intervention effects on relationship quality but couples assigned to intervention at the higher risk site were significantly less likely than controls to be divorced at the two-year follow-up (8.1% vs. 14.9%, p < .01). This effect was moderated by ethnic minority status. Specifically, the impact of the intervention on divorce was strongest for minority couples. The findings add to the literature on who may benefit most from CRE. PMID:25419027

Improving guideline concordance in multidisciplinary teams: preliminary results of a cluster-randomized trial evaluating the effect of a web-based audit and feedback intervention with outreach visits

PubMed Central

van Engen-Verheul, Mariëtte M.; Gude, Wouter T.; van der Veer, Sabine N.; Kemps, Hareld M.C.; Jaspers, Monique M.W.; de Keizer, Nicolette F.; Peek, Niels

2015-01-01

Despite their widespread use, audit and feedback (A&F) interventions show variable effectiveness on improving professional performance. Based on known facilitators of successful A&F interventions, we developed a web-based A&F intervention with indicator-based performance feedback, benchmark information, action planning and outreach visits. The goal of the intervention was to engage with multidisciplinary teams to overcome barriers to guideline concordance and to improve overall team performance in the field of cardiac rehabilitation (CR). To assess its effectiveness we conducted a cluster-randomized trial in 18 CR clinics (14,847 patients) already working with computerized decision support (CDS). Our preliminary results showed no increase in concordance with guideline recommendations regarding prescription of CR therapies. Future analyses will investigate whether our intervention did improve team performance on other quality indicators. PMID:26958310

[Daily practice using the guidelines for prevention and treatment of osteoporosis. Effectiveness of exercise for preventing and treating osteoporosis].

PubMed

Miyakoshi, Naohisa

2008-08-01

There is increasing evidence that exercise is an effective strategy for the prevention and treatment of osteoporosis. The randomized controlled trials and their meta-analyses to date, evaluating the effects of exercise on osteoporosis reveal that the exercise is effective in preserving bone mass, preventing fractures and falls, and improving quality of life in patients with osteoporosis. Emphasis is also given to the importance of the specific protocols of exercises needed to achieve positive effects safely, keeping in view the age and general physical condition of the person.

Cost-Effectiveness of Group and Internet Cognitive Behavioral Therapy for Insomnia in Adolescents: Results from a Randomized Controlled Trial.

PubMed

De Bruin, Eduard J; van Steensel, Francisca J A; Meijer, Anne Marie

2016-08-01

To investigate cost-effectiveness of adolescent cognitive behavioral therapy for insomnia (CBTI) in group- and Internet-delivered formats, from a societal perspective with a time horizon of 1 y. Costs and effects data up to 1-y follow-up were obtained from a randomized controlled trial (RCT) comparing Internet CBTI to face-to-face group CBTI. The study was conducted at the laboratory of the Research Institute of Child Development and Education at the University of Amsterdam, and the academic youth mental health care center UvAMinds in Amsterdam. Sixty-two participants meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for insomnia were randomized to face-to-face group CBTI (GT; n = 31, age = 15.6 y ± 1.8, 71.0% girls) or individual Internet CBTI (IT; n = 31, age = 15.4 y ± 1.5, 83.9% girls). The intervention consisted of six weekly sessions and a 2-mo follow up booster-session of CBTI, consisting of psychoeducation, sleep hygiene, restriction of time in bed, stimulus control, cognitive therapy, and relaxation techniques. GT sessions were held in groups of six to eight adolescents guided by two trained sleep therapists. IT consisted of individual Internet therapy with preprogrammed content similar to GT, and guided by trained sleep therapists. Outcome measures were subjective sleep efficiency (SE) ≥ 85%, and quality-adjusted life-years (QALY). Analyses were conducted from a societal perspective. Incremental cost-effectiveness ratios (ICERs) were calculated using bootstrap sampling, and presented in cost-effectiveness planes. Primary analysis showed costs over 1 y were higher for GT but effects were similar for IT and GT. Bootstrapped ICERs demonstrated there is a high probability of IT being cost-effective compared to GT. Secondary analyses confirmed robustness of results. Internet CBTI is a cost-effective treatment compared to group CBTI for adolescents, although effects were largely similar for both formats. Further studies in a clinical setting are warranted. ID: ISRCTN33922163; trial name: Effectiveness of cognitive behavioral therapy for sleeplessness in adolescents; URL: http://www.isrctn.com/ISRCTN33922163. © 2016 Associated Professional Sleep Societies, LLC.

Efficacy of group psychotherapy for social anxiety disorder: A meta-analysis of randomized-controlled trials.

PubMed

Barkowski, Sarah; Schwartze, Dominique; Strauss, Bernhard; Burlingame, Gary M; Barth, Jürgen; Rosendahl, Jenny

2016-04-01

Group psychotherapy for social anxiety disorder (SAD) is an established treatment supported by findings from primary studies and earlier meta-analyses. However, a comprehensive summary of the recent evidence is still pending. This meta-analysis investigates the efficacy of group psychotherapy for adult patients with SAD. A literature search identified 36 randomized-controlled trials examining 2171 patients. Available studies used mainly cognitive-behavioral group therapies (CBGT); therefore, quantitative analyses were done for CBGT. Medium to large positive effects emerged for wait list-controlled trials for specific symptomatology: g=0.84, 95% CI [0.72; 0.97] and general psychopathology: g=0.62, 95% CI [0.36; 0.89]. Group psychotherapy was also superior to common factor control conditions in alleviating symptoms of SAD, but not in improving general psychopathology. No differences appeared for direct comparisons of group psychotherapy and individual psychotherapy or pharmacotherapy. Hence, group psychotherapy for SAD is an efficacious treatment, equivalent to other treatment formats. Copyright © 2016 Elsevier Ltd. All rights reserved.

Emerging Evidence of Thresholds for Beneficial Effects from Vitamin D Supplementation.

PubMed

Scragg, Robert

2018-05-03

Publications from clinical trials of vitamin D supplementation have increased substantially over the last 15 years. Yet, despite the growing number of randomized controlled trials, meta-analyses of these studies have drawn inconsistent conclusions. Many meta-analyses assume that vitamin D is a pharmacological agent, and give scant consideration of it being a nutrient. This limits their potential to detect beneficial effects in participants with vitamin D deficiency. An increasing body of evidence from both observational studies and clinical trials supports the presence of thresholds in vitamin D status below which disease risk increases and vitamin supplementation has beneficial effects. Future supplementation trials which seek to replicate these findings should recruit sufficient numbers of participants with low vitamin D levels, and not give low-dose vitamin D to the placebo group. If the presence of vitamin D thresholds for beneficial effects is confirmed, this would strengthen the need for vitamin D fortification of foods.

Effect of a mobile app intervention on vegetable consumption in overweight adults: a randomized controlled trial.

PubMed

Mummah, Sarah; Robinson, Thomas N; Mathur, Maya; Farzinkhou, Sarah; Sutton, Stephen; Gardner, Christopher D

2017-09-15

Mobile applications (apps) have been heralded as transformative tools to deliver behavioral health interventions at scale, but few have been tested in rigorous randomized controlled trials. We tested the effect of a mobile app to increase vegetable consumption among overweight adults attempting weight loss maintenance. Overweight adults (n=135) aged 18-50 years with BMI=28-40 kg/m 2 near Stanford, CA were recruited from an ongoing 12-month weight loss trial (parent trial) and randomly assigned to either the stand-alone, theory-based Vegethon mobile app (enabling goal setting, self-monitoring, and feedback and using "process motivators" including fun, surprise, choice, control, social comparison, and competition) or a wait-listed control condition. The primary outcome was daily vegetables servings, measured by an adapted Harvard food frequency questionnaire (FFQ) 8 weeks post-randomization. Daily vegetable servings from 24-hour dietary recalls, administered by trained, certified, and blinded interviewers 5 weeks post-randomization, was included as a secondary outcome. All analyses were conducted according to principles of intention-to-treat. Daily vegetable consumption was significantly greater in the intervention versus control condition for both measures (adjusted mean difference: 2.0 servings; 95% CI: 0.1, 3.8, p=0.04 for FFQ; and 1.0 servings; 95% CI: 0.2, 1.9; p=0.02 for 24-hour recalls). Baseline vegetable consumption was a significant moderator of intervention effects (p=0.002) in which effects increased as baseline consumption increased. These results demonstrate the efficacy of a mobile app to increase vegetable consumption among overweight adults. Theory-based mobile interventions may present a low-cost, scalable, and effective approach to improving dietary behaviors and preventing associated chronic diseases. ClinicalTrials.gov NCT01826591. Registered 27 March 2013.

Anti-Vascular Endothelial Growth Factor Comparative Effectiveness Trial for Diabetic Macular Edema: Additional Efficacy Post Hoc Analyses of a Randomized Clinical Trial.

PubMed

Jampol, Lee M; Glassman, Adam R; Bressler, Neil M; Wells, John A; Ayala, Allison R

2016-12-01

Post hoc analyses from the Diabetic Retinopathy Clinical Research Network randomized clinical trial comparing aflibercept, bevacizumab, and ranibizumab for diabetic macular edema (DME) might influence interpretation of study results. To provide additional outcomes comparing 3 anti-vascular endothelial growth factor (VEGF) agents for DME. Post hoc analyses performed from May 3, 2016, to June 21, 2016, of a randomized clinical trial performed from August 22, 2012, to September 23, 2015, of 660 participants comparing 3 anti-VEGF treatments in eyes with center-involved DME causing vision impairment. Randomization to intravitreous aflibercept (2.0 mg), bevacizumab (1.25 mg), or ranibizumab (0.3 mg) administered up to monthly based on a structured retreatment regimen. Focal/grid laser treatment was added after 6 months for the treatment of persistent DME. Change in visual acuity (VA) area under the curve and change in central subfield thickness (CST) within subgroups based on whether an eye received laser treatment for DME during the study. Post hoc analyses were performed for 660 participants (mean [SD] age, 61 [10] years; 47% female, 65% white, 16% black or African American, 16% Hispanic, and 3% other). For eyes with an initial VA of 20/50 or worse, VA improvement was greater with aflibercept than the other agents at 1 year but superior only to bevacizumab at 2 years. Mean (SD) letter change in VA over 2 years (area under curve) was greater with aflibercept (+17.1 [9.7]) than with bevacizumab (+12.1 [9.4]; 95% CI, +1.6 to +7.3; P < .001) or ranibizumab (+13.6 [8.5]; 95% CI, +0.7 to +6.0; P = .009). When VA was 20/50 or worse at baseline, bevacizumab reduced CST less than the other agents at 1 year, but at 2 years the differences had diminished. In subgroups stratified by baseline VA, anti-VEGF agent, and whether focal/grid laser treatment was performed for DME, the only participants to have a substantial reduction in mean CST between 1 and 2 years were those with a baseline VA of 20/50 or worse receiving bevacizumab and laser treatment (mean [SD], -55 [108] µm; 95% CI, -82 to -28 µm; P < .001). Although post hoc analyses should be viewed with caution given the potential for bias, in eyes with a VA of 20/50 or worse, aflibercept has the greatest improvement in VA over 2 years. Focal/grid laser treatment, ceiling and floor effects, or both may account for mean thickness reductions noted only in bevacizumab-treated eyes between 1 and 2 years. clinicaltrials.gov Identifier NCT01627249.

Changing climates of conflict: A social network experiment in 56 schools.

PubMed

Paluck, Elizabeth Levy; Shepherd, Hana; Aronow, Peter M

2016-01-19

Theories of human behavior suggest that individuals attend to the behavior of certain people in their community to understand what is socially normative and adjust their own behavior in response. An experiment tested these theories by randomizing an anticonflict intervention across 56 schools with 24,191 students. After comprehensively measuring every school's social network, randomly selected seed groups of 20-32 students from randomly selected schools were assigned to an intervention that encouraged their public stance against conflict at school. Compared with control schools, disciplinary reports of student conflict at treatment schools were reduced by 30% over 1 year. The effect was stronger when the seed group contained more "social referent" students who, as network measures reveal, attract more student attention. Network analyses of peer-to-peer influence show that social referents spread perceptions of conflict as less socially normative.

Intervention Effects on Foster Preschoolers’ Attachment-Related Behaviors From a Randomized Trial

PubMed Central

Fisher, Philip A.; Kim, Hyoun K.

2008-01-01

This study examines change in attachment-related behaviors among foster preschoolers participating in a randomized trial of the Multidimensional Treatment Foster Care Program for Preschoolers (MTFC-P). Measures of secure, resistant, and avoidant behaviors were collected using a caregiver-report diary at 3-month intervals during the 12 months following a new foster placement. Children randomly assigned to the MTFC-P intervention condition (n = 57) showed significant increases in secure behavior and significant decreases in avoidant behavior relative to children assigned to a regular foster care condition (n = 60). Both groups showed significant decreases in resistant behavior over time. Analyses also revealed a significant interaction between treatment condition and age at first foster placement on change in secure behavior. Results are discussed in terms of the importance of early intervention and prevention services for foster preschoolers. PMID:17340186

Effectiveness and moderators of the preventive intervention kids in divorce situations: A randomized controlled trial.

PubMed

Pelleboer-Gunnink, Hannah A; Van der Valk, Inge E; Branje, Susan J T; Van Doorn, Muriel D; Deković, Maja

2015-10-01

Children of divorced parents have an increased risk of a variety of problems in comparison to children from intact families. Therefore, several intervention programs have been developed directed at children of divorced parents. Yet, empirical data on the effectiveness of these interventions are limited. This study evaluated the school-based, child-directed prevention program Kids In Divorce Situations (KIDS) using a randomized controlled trial. The sample consisted of 156 children randomly assigned at the school level into an experimental (80 children) and control condition (76 children). In addition, 131 mothers and 76 fathers participated in the study. Four assessments took place: a pretest, a posttest, and two follow-up assessments conducted 6 months and 1 year after finishing KIDS. Latent growth analyses demonstrated that the intervention significantly reduced child-reported emotional problems and enhanced child-reported communication with the father and mother-reported communication with the child. The effect sizes ranged from .30-.63. Few moderation effects of gender, time since divorce, or perceived parental conflict on the intervention effects were found. After parental divorce, a limited school-based intervention for children can be efficacious in promoting children's emotional well-being and parent-child communication. (c) 2015 APA, all rights reserved).

Language of publication restrictions in systematic reviews gave different results depending on whether the intervention was conventional or complementary.

PubMed

Pham, Ba'; Klassen, Terry P; Lawson, Margaret L; Moher, David

2005-08-01

To assess whether language of publication restrictions impact the estimates of an intervention's effectiveness, whether such impact is similar for conventional medicine and complementary medicine interventions, and whether the results are influenced by publication bias and statistical heterogeneity. We set out to examine the extent to which including reports of randomized controlled trials (RCTs) in languages other than English (LOE) influences the results of systematic reviews, using a broad dataset of 42 language-inclusive systematic reviews, involving 662 RCTs, including both conventional medicine (CM) and complementary and alternative medicine (CAM) interventions. For CM interventions, language-restricted systematic reviews, compared with language-inclusive ones, did not introduce biased results, in terms of estimates of intervention effectiveness (random effects ration of odds rations ROR=1.02; 95% CI=0.83-1.26). For CAM interventions, however, language-restricted systematic reviews resulted in a 63% smaller protective effect estimate than language-inclusive reviews (random effects ROR=1.63; 95% CI=1.03-2.60). Language restrictions do not change the results of CM systematic reviews but do substantially alter the results of CAM systematic reviews. These findings are robust even after sensitivity analyses, and do not appear to be influenced by statistical heterogeneity and publication bias.

Endurance exercise beneficially affects ambulatory blood pressure: a systematic review and meta-analysis.

PubMed

Cornelissen, Véronique A; Buys, Roselien; Smart, Neil A

2013-04-01

Exercise is widely recommended as one of the key preventive lifestyle changes to reduce the risk of hypertension and to manage high blood pressure (BP), but individual studies investigating the effect of exercise on ambulatory BP have remained inconclusive. Therefore, the primary purpose of this systematic review and meta-analysis was to determine the effect of aerobic endurance training on daytime and night-time BP in healthy adults. A systematic literature search was conducted using PubMed and Cochrane Controlled Clinical trial registry from their inception to May 2012. Randomized controlled trials of at least 4 weeks investigating the effects of aerobic endurance training on ambulatory BP in healthy adults were included. Inverse weighted random effects models were used for analyses, with data reported as weighted means and 95% confidence limits. We included 15 randomized controlled trials, involving 17 study groups and 633 participants (394 exercise participants and 239 control participants). Overall, endurance training induced a significant reduction in daytime SBP [-3.2 mmHg, 95% confidence interval (CI), -5.0 to-1.3] and daytime DBP (-2.7 mmHg, 95% CI, -3.9 to -1.5). No effect was observed on night-time BP. The findings from this meta-analysis suggest that aerobic endurance exercise significantly decreases daytime, but not night-time, ambulatory BP.

Random-effects meta-analysis: the number of studies matters.

PubMed

Guolo, Annamaria; Varin, Cristiano

2017-06-01

This paper investigates the impact of the number of studies on meta-analysis and meta-regression within the random-effects model framework. It is frequently neglected that inference in random-effects models requires a substantial number of studies included in meta-analysis to guarantee reliable conclusions. Several authors warn about the risk of inaccurate results of the traditional DerSimonian and Laird approach especially in the common case of meta-analysis involving a limited number of studies. This paper presents a selection of likelihood and non-likelihood methods for inference in meta-analysis proposed to overcome the limitations of the DerSimonian and Laird procedure, with a focus on the effect of the number of studies. The applicability and the performance of the methods are investigated in terms of Type I error rates and empirical power to detect effects, according to scenarios of practical interest. Simulation studies and applications to real meta-analyses highlight that it is not possible to identify an approach uniformly superior to alternatives. The overall recommendation is to avoid the DerSimonian and Laird method when the number of meta-analysis studies is modest and prefer a more comprehensive procedure that compares alternative inferential approaches. R code for meta-analysis according to all of the inferential methods examined in the paper is provided.

Effectiveness of virtual reality training for balance and gait rehabilitation in people with multiple sclerosis: a systematic review and meta-analysis.

PubMed

Casuso-Holgado, María Jesús; Martín-Valero, Rocío; Carazo, Ana F; Medrano-Sánchez, Esther M; Cortés-Vega, M Dolores; Montero-Bancalero, Francisco José

2018-04-01

To evaluate the evidence for the use of virtual reality to treat balance and gait impairments in multiple sclerosis rehabilitation. Systematic review and meta-analysis of randomized controlled trials and quasi-randomized clinical trials. An electronic search was conducted using the following databases: MEDLINE (PubMed), Physiotherapy Evidence Database (PEDro), Cochrane Database of Systematic Reviews (CDSR) and (CINHAL). A quality assessment was performed using the PEDro scale. The data were pooled and a meta-analysis was completed. This systematic review was conducted in accordance with the (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) PRISMA guideline statement. It was registered in the PROSPERO database (CRD42016049360). A total of 11 studies were included. The data were pooled, allowing meta-analysis of seven outcomes of interest. A total of 466 participants clinically diagnosed with multiple sclerosis were analysed. Results showed that virtual reality balance training is more effective than no intervention for postural control improvement (standard mean difference (SMD) = -0.64; 95% confidence interval (CI) = -1.05, -0.24; P = 0.002). However, significant overall effect was not showed when compared with conventional training (SMD = -0.04; 95% CI = -0.70, 0.62; P = 0.90). Inconclusive results were also observed for gait rehabilitation. Virtual reality training could be considered at least as effective as conventional training and more effective than no intervention to treat balance and gait impairments in multiple sclerosis rehabilitation.

Biases and power for groups comparison on subjective health measurements.

PubMed

Hamel, Jean-François; Hardouin, Jean-Benoit; Le Neel, Tanguy; Kubis, Gildas; Roquelaure, Yves; Sébille, Véronique

2012-01-01

Subjective health measurements are increasingly used in clinical research, particularly for patient groups comparisons. Two main types of analytical strategies can be used for such data: so-called classical test theory (CTT), relying on observed scores and models coming from Item Response Theory (IRT) relying on a response model relating the items responses to a latent parameter, often called latent trait. Whether IRT or CTT would be the most appropriate method to compare two independent groups of patients on a patient reported outcomes measurement remains unknown and was investigated using simulations. For CTT-based analyses, groups comparison was performed using t-test on the scores. For IRT-based analyses, several methods were compared, according to whether the Rasch model was considered with random effects or with fixed effects, and the group effect was included as a covariate or not. Individual latent traits values were estimated using either a deterministic method or by stochastic approaches. Latent traits were then compared with a t-test. Finally, a two-steps method was performed to compare the latent trait distributions, and a Wald test was performed to test the group effect in the Rasch model including group covariates. The only unbiased IRT-based method was the group covariate Wald's test, performed on the random effects Rasch model. This model displayed the highest observed power, which was similar to the power using the score t-test. These results need to be extended to the case frequently encountered in practice where data are missing and possibly informative.

Interaction between the FTO gene, body mass index and depression: meta-analysis of 13701 individuals†

PubMed Central

Rivera, Margarita; Locke, Adam E.; Corre, Tanguy; Czamara, Darina; Wolf, Christiane; Ching-Lopez, Ana; Milaneschi, Yuri; Kloiber, Stefan; Cohen-Woods, Sara; Rucker, James; Aitchison, Katherine J.; Bergmann, Sven; Boomsma, Dorret I.; Craddock, Nick; Gill, Michael; Holsboer, Florian; Hottenga, Jouke-Jan; Korszun, Ania; Kutalik, Zoltan; Lucae, Susanne; Maier, Wolfgang; Mors, Ole; Müller-Myhsok, Bertram; Owen, Michael J.; Penninx, Brenda W. J. H.; Preisig, Martin; Rice, John; Rietschel, Marcella; Tozzi, Federica; Uher, Rudolf; Vollenweider, Peter; Waeber, Gerard; Willemsen, Gonneke; Craig, Ian W.; Farmer, Anne E.; Lewis, Cathryn M.; Breen, Gerome; McGuffin, Peter

2017-01-01

Background Depression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity. Aims To confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis. Method The sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT. Results In the replication cohorts, we observed a significant interaction between FTO, BMI and depression with fixed effects meta-analysis (β = 0.12, P = 2.7 × 10−4) and with the Han/Eskin random effects method (P = 1.4 × 10−7) but not with traditional random effects (β = 0.1, P = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, P = 0.027) being highly significant based on the Han/Eskin model (P = 6.9 × 10−8). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of FTO. Conclusions This meta-analysis provides additional support for a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression. PMID:28642257

Does the inclusion of grey literature influence estimates of intervention effectiveness reported in meta-analyses?

PubMed

McAuley, L; Pham, B; Tugwell, P; Moher, D

2000-10-07

The inclusion of only a subset of all available evidence in a meta-analysis may introduce biases and threaten its validity; this is particularly likely if the subset of included studies differ from those not included, which may be the case for published and grey literature (unpublished studies, with limited distribution). We set out to examine whether exclusion of grey literature, compared with its inclusion in meta-analysis, provides different estimates of the effectiveness of interventions assessed in randomised trials. From a random sample of 135 meta-analyses, we identified and retrieved 33 publications that included both grey and published primary studies. The 33 publications contributed 41 separate meta-analyses from several disease areas. General characteristics of the meta-analyses and associated studies and outcome data at the trial level were collected. We explored the effects of the inclusion of grey literature on the quantitative results using logistic-regression analyses. 33% of the meta-analyses were found to include some form of grey literature. The grey literature, when included, accounts for between 4.5% and 75% of the studies in a meta-analysis. On average, published work, compared with grey literature, yielded significantly larger estimates of the intervention effect by 15% (ratio of odds ratios=1.15 [95% CI 1.04-1.28]). Excluding abstracts from the analysis further compounded the exaggeration (1.33 [1.10-1.60]). The exclusion of grey literature from meta-analyses can lead to exaggerated estimates of intervention effectiveness. In general, meta-analysts should attempt to identify, retrieve, and include all reports, grey and published, that meet predefined inclusion criteria.

Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium.

PubMed

Skaaby, Tea; Taylor, Amy E; Jacobsen, Rikke K; Paternoster, Lavinia; Thuesen, Betina H; Ahluwalia, Tarunveer S; Larsen, Sofus C; Zhou, Ang; Wong, Andrew; Gabrielsen, Maiken E; Bjørngaard, Johan H; Flexeder, Claudia; Männistö, Satu; Hardy, Rebecca; Kuh, Diana; Barry, Sarah J; Tang Møllehave, Line; Cerqueira, Charlotte; Friedrich, Nele; Bonten, Tobias N; Noordam, Raymond; Mook-Kanamori, Dennis O; Taube, Christian; Jessen, Leon E; McConnachie, Alex; Sattar, Naveed; Upton, Mark N; McSharry, Charles; Bønnelykke, Klaus; Bisgaard, Hans; Schulz, Holger; Strauch, Konstantin; Meitinger, Thomas; Peters, Annette; Grallert, Harald; Nohr, Ellen A; Kivimaki, Mika; Kumari, Meena; Völker, Uwe; Nauck, Matthias; Völzke, Henry; Power, Chris; Hyppönen, Elina; Hansen, Torben; Jørgensen, Torben; Pedersen, Oluf; Salomaa, Veikko; Grarup, Niels; Langhammer, Arnulf; Romundstad, Pål R; Skorpen, Frank; Kaprio, Jaakko; R Munafò, Marcus; Linneberg, Allan

2017-05-22

Observational studies on smoking and risk of hay fever and asthma have shown inconsistent results. However, observational studies may be biased by confounding and reverse causation. Mendelian randomization uses genetic variants as markers of exposures to examine causal effects. We examined the causal effect of smoking on hay fever and asthma by using the smoking-associated single nucleotide polymorphism (SNP) rs16969968/rs1051730. We included 231,020 participants from 22 population-based studies. Observational analyses showed that current vs never smokers had lower risk of hay fever (odds ratio (OR) = 0·68, 95% confidence interval (CI): 0·61, 0·76; P < 0·001) and allergic sensitization (OR = 0·74, 95% CI: 0·64, 0·86; P < 0·001), but similar asthma risk (OR = 1·00, 95% CI: 0·91, 1·09; P = 0·967). Mendelian randomization analyses in current smokers showed a slightly lower risk of hay fever (OR = 0·958, 95% CI: 0·920, 0·998; P = 0·041), a lower risk of allergic sensitization (OR = 0·92, 95% CI: 0·84, 1·02; P = 0·117), but higher risk of asthma (OR = 1·06, 95% CI: 1·01, 1·11; P = 0·020) per smoking-increasing allele. Our results suggest that smoking may be causally related to a higher risk of asthma and a slightly lower risk of hay fever. However, the adverse events associated with smoking limit its clinical significance.

The Use of Footstep Sounds as Rhythmic Auditory Stimulation for Gait Rehabilitation in Parkinson's Disease: A Randomized Controlled Trial.

PubMed

Murgia, Mauro; Pili, Roberta; Corona, Federica; Sors, Fabrizio; Agostini, Tiziano A; Bernardis, Paolo; Casula, Carlo; Cossu, Giovanni; Guicciardi, Marco; Pau, Massimiliano

2018-01-01

The use of rhythmic auditory stimulation (RAS) has been proven useful in the management of gait disturbances associated with Parkinson's disease (PD). Typically, the RAS consists of metronome or music-based sounds (artificial RAS), while ecological footstep sounds (ecological RAS) have never been used for rehabilitation programs. The aim of this study was to compare the effects of a rehabilitation program integrated either with ecological or with artificial RAS. An observer-blind, randomized controlled trial was conducted to investigate the effects of 5 weeks of supervised rehabilitation integrated with RAS. Thirty-eight individuals affected by PD were randomly assigned to one of the two conditions (ecological vs. artificial RAS); thirty-two of them (age 68.2 ± 10.5, Hoehn and Yahr 1.5-3) concluded all phases of the study. Spatio-temporal parameters of gait and clinical variables were assessed before the rehabilitation period, at its end, and after a 3-month follow-up. Thirty-two participants were analyzed. The results revealed that both groups improved in the majority of biomechanical and clinical measures, independently of the type of sound. Moreover, exploratory analyses for separate groups were conducted, revealing improvements on spatio-temporal parameters only in the ecological RAS group. Overall, our results suggest that ecological RAS is equally effective compared to artificial RAS. Future studies should further investigate the role of ecological RAS, on the basis of information revealed by our exploratory analyses. Theoretical, methodological, and practical issues concerning the implementation of ecological sounds in the rehabilitation of PD patients are discussed. www.ClinicalTrials.gov, identifier NCT03228888.

Patient-centered Outcomes with Concomitant Use of Proton Pump Inhibitors and Other Drugs.

PubMed

Shamliyan, Tatyana A; Middleton, Maria; Borst, Clarissa

2017-02-01

We performed a systematic review of patient-centered outcomes after the concomitant use of proton pump inhibitors (PPIs) and other drugs. We searched 4 databases in July 2016 to find studies that reported mortality and morbidity after the concomitant use of PPIs and other drugs. We conducted direct meta-analyses using a random-effects model and graded the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation working group approach. We included data from 17 systematic reviews and meta-analyses, 16 randomized controlled trials, and 16 observational studies that examined the concomitant use of PPIs with medications from 10 drug classes. Low-quality evidence suggests that the use of PPIs is associated with greater morbidity when administered with antiplatelet drugs, bisphosphonates, antibiotics, anticoagulants, metformin, mycophenolate mofetil, or nelfinavir. Concomitant PPIs reduce drug-induced gastrointestinal bleeding and are associated with greater docetaxel and cisplatin response rates in patients with metastatic breast cancer. For demonstrated statistically significant relative risks and benefits from concomitant PPIs, the magnitudes of the effects are small, with <100 attributable events per 1000 patients treated, and the effects are inconsistent among specific drugs. Among individual PPIs, the concomitant use of pantoprazole or esomeprazole, but not omeprazole or lansoprazole, is associated with an increased risk for all-cause mortality, nonfatal myocardial infarction, or stroke. Clopidogrel is associated with a greater risk for myocardial infarction compared with prasugrel. Conflicting results between randomized controlled trials and observational studies and high risk for bias in the body of evidence lessened our confidence in the results. Available evidence suggests a greater risk for adverse patient outcomes after the concomitant use of PPIs and medications from 9 drug classes and warns against inappropriate drug combinations. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Specific collaborative group intervention for patients with medically unexplained symptoms in general practice: a cluster randomized controlled trial.

PubMed

Schaefert, R; Kaufmann, C; Wild, B; Schellberg, D; Boelter, R; Faber, R; Szecsenyi, J; Sauer, N; Guthrie, E; Herzog, W

2013-01-01

Patients with medically unexplained symptoms (MUS) are frequent in primary care and substantially impaired in their quality of life (QoL). Specific training of general practitioners (GPs) alone did not demonstrate sustained improvement at later follow-up in current reviews. We evaluated a collaborative group intervention. We conducted a cluster randomized controlled trial. Thirty-five GPs recruited 304 MUS patients (intervention group: 170; control group: 134). All GPs were trained in diagnosis and management of MUS (control condition). Eighteen randomly selected intervention GPs participated in training for a specific collaborative group intervention. They conducted 10 weekly group sessions and 2 booster meetings in their practices, together with a psychosomatic specialist. Six and 12 months after baseline, QoL was assessed with the Short-Form 36. The primary outcome was the physical composite score (PCS), and the secondary outcome was the mental composite score (MCS). At 12 months, intention-to-treat analyses showed a significant between-group effect for the MCS (p = 0.023) but not for the PCS (p = 0.674). This effect was preceded by a significant reduction of somatic symptom severity (15-item somatic symptom severity scale of the Patient Health Questionnaire, PHQ-15) at 6 months (p = 0.008) that lacked significance at 12 months (p = 0.078). As additional between-group effects at 12 months, per-protocol analyses showed less health anxiety (Whiteley-7; p = 0.038) and less psychosocial distress (PHQ; p = 0.024); GP visits were significantly (p = 0.042) reduced in the intervention group. Compared to pure GP training, collaborative group intervention achieved a progressive, clinically meaningful improvement in mental but not physical QoL. It could bridge gaps between general practice and mental health care. Copyright © 2012 S. Karger AG, Basel.

Trauma and recent life events in individuals at ultra high risk for psychosis: review and meta-analysis.

PubMed

Kraan, Tamar; Velthorst, Eva; Smit, Filip; de Haan, Lieuwe; van der Gaag, Mark

2015-02-01

Childhood trauma and recent life-events have been related to psychotic disorders. The aim of the present study was to examine whether childhood trauma and recent life-events are significantly more prevalent in patients at Ultra High Risk (UHR) of developing a psychotic disorder compared to healthy controls. A search of PsychInfo and Embase was conducted, relevant papers were reviewed, and three random-effects meta-analyses were performed. One meta-analysis assessed the prevalence rate of childhood trauma in UHR subjects and two meta-analyses were conducted to compare UHR subjects and healthy control subjects on the experience of childhood trauma and recent life-events. We found 12 studies on the prevalence of (childhood) trauma in UHR populations and 4 studies on recent life-events in UHR populations. We performed a meta-analysis on 6 studies (of which trauma prevalence rates were available) on childhood trauma in UHR populations, yielding a mean prevalence rate of 86.8% (95% CI 77%-93%). Childhood trauma was significantly more prevalent in UHR subjects compared to healthy control groups (Random effects Hedges' g=1.09; Z=4.60, p<.001). In contrast to our hypothesis, life-event rates were significantly lower in UHR subjects compared to healthy controls (Random effects Hedges' g=-0.53; Z=-2.36, p<.02). Our meta-analytic results illustrate that childhood trauma is highly prevalent among UHR subjects and that childhood trauma is related to UHR status. These results are in line with studies on childhood trauma in psychotic populations. In contrast to studies on recent life-events in psychotic populations, our results show that recent life-events are not associated with UHR status. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects on agitation with rivastigmine patch monotherapy and combination therapy with memantine in mild to moderate Alzheimer's disease: a multicenter 24-week prospective randomized open-label study (the Korean EXelon Patch and combination with mEmantine Comparative Trial study).

PubMed

Yoon, Soo J; Choi, Seong H; Na, Hae R; Park, Kyung-Won; Kim, Eun-Joo; Han, Hyun J; Lee, Jae-Hong; Shim, Young S; Na, Duk L

2017-03-01

Memantine is known to be effective in the treatment of the behavioral symptoms of dementia, especially agitation in moderate to severe Alzheimer's disease (AD). However, memantine and rivastigmine patch combination therapy has not been well studied in determining treatment effectiveness with mild to moderate AD patients. This was a multicenter, 24-week, prospective, randomized, open-label study design. A total 147 AD patients with Mini-Mental State Examination scores from 10 to 20 were randomly assigned to rivastigmine patch monotherapy and combination therapy with memantine groups. Agitation symptoms, using the Korean Version of the Cohen Mansfield Agitation Inventory were evaluated at baseline and at study end. Suppression and emergence of agitation symptoms were also evaluated. We carried out factor analyses to evaluate the interrelationship of agitation symptoms and to investigate treatment response in these symptoms. Factor analyses showed two symptom clusters: factor A - aggressive agitated behaviors - versus factor B - non-aggressive agitated behaviors. The rivastigmine patch monotherapy group showed significantly decreased factor B scores and had a tendency of decreased Korean Version of the Cohen Mansfield Agitation Inventory total scores and factor A scores. Conversely, the combination therapy group showed significantly increased Korean Version of the Cohen Mansfield Agitation Inventory total scores and factor B scores. Neither monotherapy nor combination therapy reduced the emergence of new agitation symptoms. In this trial of mild to moderate AD patients, the rivastigmine patch monotherapy group experienced a reduction of non-aggressive agitated behaviors. However, combination therapy with memantine did not show any benefit on the agitation associated with mild to moderate AD. Geriatr Gerontol Int 2017; 17: 494-499. © 2016 Japan Geriatrics Society.

Efficacy of Psychotherapies for Borderline Personality Disorder: A Systematic Review and Meta-analysis.

PubMed

Cristea, Ioana A; Gentili, Claudio; Cotet, Carmen D; Palomba, Daniela; Barbui, Corrado; Cuijpers, Pim

2017-04-01

Borderline personality disorder (BPD) is a debilitating condition, but several psychotherapies are considered effective. To conduct an updated systematic review and meta-analysis of randomized clinical trials to assess the efficacy of psychotherapies for BPD populations. Search terms were combined for borderline personality and randomized trials in PubMed, PsycINFO, EMBASE, and the Cochrane Central Register of Controlled Trials (from database inception to November 2015), as well as the reference lists of earlier meta-analyses. Included were randomized clinical trials of adults with diagnosed BPD randomized to psychotherapy exclusively or to a control intervention. Study selection differentiated stand-alone designs (in which an independent psychotherapy was compared with control interventions) from add-on designs (in which an experimental intervention added to usual treatment was compared with usual treatment alone). Data extraction coded characteristics of trials, participants, and interventions and assessed risk of bias using 4 domains of the Cochrane Collaboration Risk of Bias tool (independent extraction by 2 assessors). Outcomes were pooled using a random-effects model. Subgroup and meta-regression analyses were conducted. Standardized mean differences (Hedges g) were calculated using all outcomes reported in the trials for borderline symptoms, self-harm, suicide, health service use, and general psychopathology at posttest and follow-up. Differential treatment retention at posttest was analyzed, reporting odds ratios. Thirty-three trials (2256 participants) were included. For borderline-relevant outcomes combined (symptoms, self-harm, and suicide) at posttest, the investigated psychotherapies were moderately more effective than control interventions in stand-alone designs (g = 0.32; 95% CI, 0.14-0.51) and add-on designs (g = 0.40; 95% CI, 0.15-0.65). Results were similar for other outcomes, including stand-alone designs: self-harm (g = 0.32; 95% CI, 0.09-0.54), suicide (g = 0.44; 95% CI, 0.15-0.74), health service use (g = 0.40; 95% CI, 0.22-0.58), and general psychopathology (g = 0.32; 95% CI, 0.09-0.55), with no differences between design types. There were no significant differences in the odds ratios for treatment retention (1.32; 95% CI, 0.87-2.00 for stand-alone designs and 1.01; 95% CI, 0.55-1.87 for add-on designs). Thirteen trials reported borderline-relevant outcomes at follow-up (g = 0.45; 95% CI, 0.15-0.75). Dialectical behavior therapy (g = 0.34; 95% CI, 0.15-0.53) and psychodynamic approaches (g = 0.41; 95% CI, 0.12-0.69) were the only types of psychotherapies more effective than control interventions. Risk of bias was a significant moderator in subgroup and meta-regression analyses (slope β = -0.16; 95% CI, -0.29 to -0.03; P = .02). Publication bias was persistent, particularly for follow-up. Psychotherapies, most notably dialectical behavior therapy and psychodynamic approaches, are effective for borderline symptoms and related problems. Nonetheless, effects are small, inflated by risk of bias and publication bias, and particularly unstable at follow-up.

Effects of green tea catechins with or without caffeine on glycemic control in adults: a meta-analysis of randomized controlled trials.

PubMed

Zheng, Xin-Xin; Xu, Yan-Lu; Li, Shao-Hua; Hui, Rutai; Wu, Yong-Jian; Huang, Xiao-Hong

2013-04-01

The effect of green tea catechins (GTCs) with or without caffeine on glycemic control is controversial. We aimed to identify and quantify the effects of GTCs or GTC-caffeine mixtures on glucose metabolism in adults. A comprehensive literature search was conducted to identify relevant trials of GTCs with or without caffeine on markers of glycemic control [fasting blood glucose (FBG), fasting blood insulin (FBI), glycated hemoglobin (Hb A1c), and homeostatic model assessment of insulin resistance (HOMA-IR)]. Weighted mean differences were calculated for net changes by using fixed-effects models. Prespecified subgroup analyses were performed to explore the influence of covariates on net changes in FBG and FBI concentrations. Twenty-two eligible randomized controlled trials with 1584 subjects were identified. Pooled analyses showed that FBG (-1.48 mg/dL; 95% CI: -2.57, -0.40 mg/dL) decreased significantly with GTCs with or without caffeine, whereas FBI (0.04 μU/mL; 95% CI: -0.36, 0.45 μU/mL), Hb A1c (-0.04%; 95% CI: -0.15, 0.08%), and HOMA-IR (-0.05; 95% CI: -0.37, 0.26) did not. Subgroup analyses indicated that the glucose-lowering effect was apparent when the duration of follow-up was over a median of 12 wk. Overall, no significant heterogeneity was detected for FBG, FBI, Hb A1c, or HOMA-IR. The meta-analysis showed that the administration of GTCs with or without caffeine resulted in a significant reduction in FBG. The limited data available on GTCs did not support a positive effect on FBI, Hb A1c, or HOMA-IR. Thus, more large and well-designed trials are needed in the future. This trial was registered at http://www.crd.york.ac.uk/prospero as CRD42012002139.

Practice facilitation for improving cardiovascular care: secondary evaluation of a stepped wedge cluster randomized controlled trial using population-based administrative data.

PubMed

Deri Armstrong, Catherine; Taljaard, Monica; Hogg, William; Mark, Amy E; Liddy, Clare

2016-09-05

Practice facilitation (PF), a multifaceted approach in which facilitators (external health care professionals) help family physicians to improve their adoption of best practices, has been highly successful. Improved Delivery of Cardiovascular Care (IDOCC) was an innovative PF trial designed to improve evidence-based care for people who have, or are at risk of, cardiovascular disease (CVD). The intervention was found to be ineffective as assessed by a patient-level composite score based on chart reviews from a subsample of patients (N = 5292). Here, we used population-based administrative data to examine IDOCC's effect on CVD-related hospitalizations. IDOCC used a pragmatic, stepped wedge cluster randomized controlled design involving primary care providers recruited across Eastern Ontario, Canada. IDOCC's effect on CVD-related hospitalizations was assessed in the 2 years of active intervention and post-intervention years. Marginal and mixed-effects regression analyses were used to account for the study design and to control for patient, physician, and practice characteristics. Secondary and subgroup analyses investigated robustness. Our sample included 262,996 patient/year observations representing 54,085 unique patients who had, or were at risk of, CVD, from 70 practices. There was a strong decreasing secular trend in CVD-related hospitalizations but no statistically significant effect of IDOCC. Relative to patients in the control condition, patients in the intervention condition were estimated to have 4 % lower odds of CVD-related hospitalizations (adjOR = 0.96, 99 % CI 0.83 to 1.11). The nonsignificant result persisted across robustness analyses. Clinical outcomes from administrative databases were examined to form a more complete picture of the (in)effectiveness of a large-scale quality improvement intervention. IDOCC did not have a significant effect on CVD hospitalizations, suggesting that the results from the primary composite adherence score analysis were neither due to choice of outcome nor relatively short follow-up period. ClinicalTrials.gov NCT00574808 , registered on 14 December 2007.

Effect and Process Evaluation of a Cluster Randomized Control Trial on Water Intake and Beverage Consumption in Preschoolers from Six European Countries: The ToyBox-Study

PubMed Central

Pinket, An-Sofie; Van Lippevelde, Wendy; De Bourdeaudhuij, Ilse; Deforche, Benedicte; Cardon, Greet; Androutsos, Odysseas; Koletzko, Berthold; Moreno, Luis A.; Socha, Piotr; Iotova, Violeta; Manios, Yannis; De Craemer, Marieke

2016-01-01

Background Within the ToyBox-study, a kindergarten-based, family-involved intervention was developed to prevent overweight and obesity in European preschoolers, targeting four key behaviours related to early childhood obesity, including water consumption. The present study aimed to examine the effect of the ToyBox-intervention (cluster randomized controlled trial) on water intake and beverage consumption in European preschoolers and to investigate if the intervention effects differed by implementation score of kindergartens and parents/caregivers. Method A sample of 4964 preschoolers (4.7±0.4 years; 51.5% boys) from six European countries (Belgium, Bulgaria, Germany, Greece, Poland, Spain) was included in the data analyses. A standardized protocol was used and parents/caregivers filled in socio-demographic data and a food-frequency questionnaire. To assess intervention effects, multilevel repeated measures analyses were conducted for the total sample and for the six country-specific samples. Based on the process evaluation questionnaire of teachers and parents/caregivers, an implementation score was constructed. To assess differences in water intake and beverage consumption by implementation score in the total sample, multilevel repeated measures analyses were performed. Results Limited intervention effects on water intake from beverages and overall beverage consumption were found. However, important results were found on prepacked fruit juice consumption, with a larger decrease in the intervention group compared to the control group. However, also a decline in plain milk consumption was found. Implementation scores were rather low in both kindergartens and parents/caregivers. Nevertheless, more favorable effects on beverage choices were found in preschoolers whose parents/caregivers and kindergarten teachers had higher implementation scores compared to those with lower implementation scores. Conclusion The ToyBox-intervention can provide the basis for the development of more tailor-made interventions. However, new strategies to improve implementation of interventions should be created. PMID:27064274

Effects of garlic on blood pressure in patients with and without systolic hypertension: a meta-analysis.

PubMed

Reinhart, Kurt M; Coleman, Craig I; Teevan, Colleen; Vachhani, Payal; White, C Michael

2008-12-01

Garlic has been suggested to lower blood pressure; however, studies evaluating this parameter have provided conflicting results. To examine the effect of garlic on blood pressure in patients with and without elevated systolic blood pressure (SPB) through meta-analyses of randomized controlled trials. A systematic search of MEDLINE, CINAHL, and the Cochrane Central Register of Controlled Trials was conducted to identify randomized controlled trials in humans evaluating garlic's effect on blood pressure. All databases were searched from their inception through June 26, 2008, using the key words garlic, Allium sativum, and allicin. A manual search of published literature was used to identify additional relevant studies. To be included in the analysis, studies must have been written in English or German and reported endpoints of SBP or diastolic blood pressure (DBP). Studies whose population had a mean baseline SBP greater than 140 mm Hg were evaluated separately from those whose population had lower baseline blood pressures. Garlic's effect on SBP and DBP was treated as a continuous variable and weighted mean differences were calculated using a random-effects model. Ten trials were included in the analysis; 3 of these had patients with elevated SBP. Garlic reduced SBP by 16.3 mm Hg (95% CI 6.2 to 26.5) and DBP by 9.3 mm Hg (95% CI 5.3 to 13.3) compared with placebo in patients with elevated SBP. However, the use of garlic did not reduce SBP or DBP in patients without elevated SBP. There was only a minor degree of heterogeneity in the analyses and publication bias did not appear to influence the results. This meta-analysis suggests that garlic is associated with blood pressure reductions in patients with an elevated SBP although not in those without elevated SBP. Future research should focus on the impact of garlic on clinical events and the assessment of the long-term risk of harm.

Evaluation of the UP4FUN Intervention: A Cluster Randomized Trial to Reduce and Break Up Sitting Time in European 10-12-Year-Old Children

PubMed Central

Vik, Frøydis N.; Lien, Nanna; Berntsen, Sveinung; De Bourdeaudhuij, Ilse; Grillenberger, Monika; Manios, Yannis; Kovacs, Eva; Chinapaw, Mai J. M.; Brug, Johannes; Bere, Elling

2015-01-01

Background The UP4FUN intervention is a family-involved school-based intervention aiming at reducing and breaking up sitting time at home (with special emphasis on screen time), and breaking up sitting time in school among 10–12 year olds in Europe. The purpose of the present paper was to evaluate its short term effects. Methodology/Principal Findings A total of 3147 pupils from Belgium, Germany, Greece, Hungary and Norway participated in a school-randomized controlled trial. The intervention included 1–2 school lessons per week for a period of six weeks, along with assignments for the children and their parents. Screen time and breaking up sitting time were registered by self-report and total sedentary time and breaking up sitting time by accelerometry. The effect of the intervention on these behaviors was evaluated by multilevel regression analyses. All analyses were adjusted for baseline values and gender. Significance level was p≤0.01. No significant intervention effects were observed, neither for self-reported TV/DVD or computer/game console time, nor for accelerometer-assessed total sedentary time and number of breaks in sitting time. The intervention group, however, reported more positive attitudes towards (β = 0.25 (95% CI 0.11, 0.38)) and preferences/liking for (β = 0.20 (95% CI 0.08, 0.32)) breaking up sitting time than the control group. Conclusions/Significance No significant intervention effect on self-reported screen time or accelerometer-assessed sedentary time or breaks in sitting time was observed, but positive effects on beliefs regarding breaking up sitting time were found in favor of the intervention group. Overall, these results do not warrant wider dissemination of the present UP4FUN intervention. Trial Registration International Standard Randomized Controlled Trial Number Registry ISRCTN34562078 PMID:25826704

Effects of a social accountability approach, CARE's Community Score Card, on reproductive health-related outcomes in Malawi: A cluster-randomized controlled evaluation.

PubMed

Gullo, Sara; Galavotti, Christine; Sebert Kuhlmann, Anne; Msiska, Thumbiko; Hastings, Phil; Marti, C Nathan

2017-01-01

Social accountability approaches, which emphasize mutual responsibility and accountability by community members, health care workers, and local health officials for improving health outcomes in the community, are increasingly being employed in low-resource settings. We evaluated the effects of a social accountability approach, CARE's Community Score Card (CSC), on reproductive health outcomes in Ntcheu district, Malawi using a cluster-randomized control design. We matched 10 pairs of communities, randomly assigning one from each pair to intervention and control arms. We conducted two independent cross-sectional surveys of women who had given birth in the last 12 months, at baseline and at two years post-baseline. Using difference-in-difference (DiD) and local average treatment effect (LATE) estimates, we evaluated the effects on outcomes including modern contraceptive use, antenatal and postnatal care service utilization, and service satisfaction. We also evaluated changes in indicators developed by community members and service providers in the intervention areas. DiD analyses showed significantly greater improvements in the proportion of women receiving a home visit during pregnancy (B = 0.20, P < .01), receiving a postnatal visit (B = 0.06, P = .01), and overall service satisfaction (B = 0.16, P < .001) in intervention compared to control areas. LATE analyses estimated significant effects of the CSC intervention on home visits by health workers (114% higher in intervention compared to control) (B = 1.14, P < .001) and current use of modern contraceptives (57% higher) (B = 0.57, P < .01). All 13 community- and provider-developed indicators improved, with 6 of them showing significant improvements. By facilitating the relationship between community members, health service providers, and local government officials, the CSC contributed to important improvements in reproductive health-related outcomes. Further, the CSC builds mutual accountability, and ensures that solutions to problems are locally-relevant, locally-supported and feasible to implement.

Effects of the Opioid Receptor Antagonist Naltrexone on Smoking and Related Behaviors in Smokers Preparing to Quit: A Randomized Controlled Trial

PubMed Central

King, Andrea; Cao, Dingcai; Zhang, Lingjiao; Rueger, Sandra Yu

2013-01-01

Aims To determine if naltrexone affects smoking behaviours in smokers preparing to quit, and whether such pre-quit responses predict post-quit date outcomes. Design Double-blind, placebo-controlled, randomized study. Current study focused on smoking-related outcomes in the pre-quit phase, which was one week prior to the quit date, and these findings were linked with reductions in same outcomes demonstrated in the post-quit phase previously published for this RCT in mediation analyses. Setting Community sample of adult smokers desiring to quit in Chicago, Illinois USA. Participants Participants were 315 smokers randomized to naltrexone (n=161; mean age=42.6 years; 60% white) or placebo (n=154; mean age=41.3 years; 55% white). Measurements Difference from baseline in the number of cigarettes smoked during pre-quit phase interval was the primary outcome. Secondary pre-quit outcomes were assessed using Likert scales of subjective responses and consumption of cigarettes, alcohol, and food. Number of cigarettes smoked, alcoholic drinks consumed, and the Brief Questionnaire of Smoking Urges were assessed in the post-quit phase. Findings Relative to placebo, naltrexone decreased the number of cigarettes smoked (−4.21 vs. −2.93, p<.05), smoking urge (p=.02), and number of alcoholic drinks consumed (p=.04). Exploratory mediation analyses linking outcomes of the pre quit and post quit phases found that naltrexone’s effects on reducing smoking urge, cigarettes smoked and alcoholic drinks consumed in the pre-quit phase demonstrated full mediation of their respective effects during the post-quit phase. Conclusions Naltrexone taken in the week before a quit attempt appears to reduce cigarette consumption, urges to smoke and alcohol consumption relative to placebo. The size of the effect statistically mediates the size of similar effects after the quit date. PMID:23714324

Circle of Security–Parenting: A randomized controlled trial in Head Start

PubMed Central

CASSIDY, JUDE; BRETT, BONNIE E.; GROSS, JACQUELYN T.; STERN, JESSICA A.; MARTIN, DAVID R.; MOHR, JONATHAN J.; WOODHOUSE, SUSAN S.

2017-01-01

Although evidence shows that attachment insecurity and disorganization increase risk for the development of psychopathology (Fearon, Bakermans-Kranenburg, van IJzendoorn, Lapsley, & Roisman, 2010; Groh, Roisman, van IJzendoorn, Bakermans-Kranenburg, & Fearon, 2012), implementation challenges have precluded dissemination of attachment interventions on the broad scale at which they are needed. The Circle of Security–Parenting Intervention (COS-P; Cooper, Hoffman, & Powell, 2009), designed with broad implementation in mind, addresses this gap by training community service providers to use a manualized, video-based program to help caregivers provide a secure base and a safe haven for their children. The present study is a randomized controlled trial of COS-P in a low-income sample of Head Start enrolled children and their mothers. Mothers (N = 141; 75 intervention, 66 waitlist control) completed a baseline assessment and returned with their children after the 10-week intervention for the outcome assessment, which included the Strange Situation. Intent to treat analyses revealed a main effect for maternal response to child distress, with mothers assigned to COS-P reporting fewer unsupportive (but not more supportive) responses to distress than control group mothers, and a main effect for one dimension of child executive functioning (inhibitory control but not cognitive flexibility when maternal age and marital status were controlled), with intervention group children showing greater control. There were, however, no main effects of intervention for child attachment or behavior problems. Exploratory follow-up analyses suggested intervention effects were moderated by maternal attachment style or depressive symptoms, with moderated intervention effects emerging for child attachment security and disorganization, but not avoidance; for inhibitory control but not cognitive flexibility; and for child internalizing but not externalizing behavior problems. This initial randomized controlled trial of the efficacy of COS-P sets the stage for further exploration of “what works for whom” in attachment intervention. PMID:28401843

Cost-Utility of Group Acceptance and Commitment Therapy for Fibromyalgia Versus Recommended Drugs: An Economic Analysis Alongside a 6-Month Randomized Controlled Trial Conducted in Spain (EFFIGACT Study).

PubMed

Luciano, Juan V; D'Amico, Francesco; Feliu-Soler, Albert; McCracken, Lance M; Aguado, Jaume; Peñarrubia-María, María T; Knapp, Martin; Serrano-Blanco, Antoni; García-Campayo, Javier

2017-07-01

The aim of this study was to analyze the cost utility of a group-based form of acceptance and commitment therapy (GACT) in patients with fibromyalgia (FM) compared with patients receiving recommended pharmacological treatment (RPT) or on a waiting list (WL). The data were derived from a previously published study, a randomized controlled trial that focused on clinical outcomes. Health economic outcomes included health-related quality of life and health care use at baseline and at 6-month follow-up using the EuroQoL and the Client Service Receipt Inventory, respectively. Analyses included quality-adjusted life years, direct and indirect cost differences, and incremental cost effectiveness ratios. A total of 156 FM patients were randomized (51 GACT, 52 RPT, 53 WL). GACT was related to significantly less direct costs over the 6-month study period compared with both control arms (GACT €824.2 ± 1,062.7 vs RPT €1,730.7 ± 1,656.8 vs WL €2,462.7 ± 2,822.0). Lower direct costs for GACT compared with RPT were due to lower costs from primary care visits and FM-related medications. The incremental cost effectiveness ratios were dominant in the completers' analysis and remained robust in the sensitivity analyses. In conclusion, acceptance and commitment therapy appears to be a cost-effective treatment compared with RPT in patients with FM. Decision-makers have to prioritize their budget on the treatment option that is the most cost effective for the management of a specific patient group. From government as well as health care perspectives, this study shows that a GACT is more cost effective than pharmacological treatment in management of FM. Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.

Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials.

PubMed

Hooper, Lee; Kay, Colin; Abdelhamid, Asmaa; Kroon, Paul A; Cohn, Jeffrey S; Rimm, Eric B; Cassidy, Aedín

2012-03-01

There is substantial interest in chocolate and flavan-3-ols for the prevention of cardiovascular disease (CVD). The objective was to systematically review the effects of chocolate, cocoa, and flavan-3-ols on major CVD risk factors. We searched Medline, EMBASE, and Cochrane databases for randomized controlled trials (RCTs) of chocolate, cocoa, or flavan-3-ols. We contacted authors for additional data and conducted duplicate assessment of study inclusion, data extraction, validity, and random-effects meta-analyses. We included 42 acute or short-term chronic (≤18 wk) RCTs that comprised 1297 participants. Insulin resistance (HOMA-IR: -0.67; 95% CI: -0.98, -0.36) was improved by chocolate or cocoa due to significant reductions in serum insulin. Flow-mediated dilatation (FMD) improved after chronic (1.34%; 95% CI: 1.00%, 1.68%) and acute (3.19%; 95% CI: 2.04%, 4.33%) intakes. Effects on HOMA-IR and FMD remained stable to sensitivity analyses. We observed reductions in diastolic blood pressure (BP; -1.60 mm Hg; 95% CI: -2.77, -0.43 mm Hg) and mean arterial pressure (-1.64 mm Hg; 95% CI: -3.27, -0.01 mm Hg) and marginally significant effects on LDL (-0.07 mmol/L; 95% CI: -0.13, 0.00 mmol/L) and HDL (0.03 mmol/L; 95% CI: 0.00, 0.06 mmol/L) cholesterol. Chocolate or cocoa improved FMD regardless of the dose consumed, whereas doses >50 mg epicatechin/d resulted in greater effects on systolic and diastolic BP. GRADE (Grading of Recommendations, Assessment, Development and Evaluation, a tool to assess quality of evidence and strength of recommendations) suggested low- to moderate-quality evidence of beneficial effects, with no suggestion of negative effects. The strength of evidence was lowered due to unclear reporting for allocation concealment, dropouts, missing data on outcomes, and heterogeneity in biomarker results in some studies. We found consistent acute and chronic benefits of chocolate or cocoa on FMD and previously unreported promising effects on insulin and HOMA-IR. Larger, longer-duration, and independently funded trials are required to confirm the potential cardiovascular benefits of cocoa flavan-3-ols.

The Effectiveness of Lifestyle Triple P in the Netherlands: A Randomized Controlled Trial

PubMed Central

Gerards, Sanne M. P. L.; Dagnelie, Pieter C.; Gubbels, Jessica S.; van Buuren, Stef; Hamers, Femke J. M.; Jansen, Maria W. J.; van der Goot, Odilia H. M.; de Vries, Nanne K.; Sanders, Matthew R.; Kremers, Stef P. J.

2015-01-01

Introduction Lifestyle Triple P is a general parenting intervention which focuses on preventing further excessive weight gain in overweight and obese children. The objective of the current study was to assess the effectiveness of the Lifestyle Triple P intervention in the Netherlands. Method We used a parallel randomized controlled design to test the effectiveness of the intervention. In total, 86 child-parent triads (children 4–8 years old, overweight or obese) were recruited and randomly assigned (allocation ratio 1:1) to the Lifestyle Triple P intervention or the control condition. Parents in the intervention condition received a 14-week intervention consisting of ten 90-minute group sessions and four individual telephone sessions. Primary outcome measure was the children’s body composition (BMI z-scores, waist circumference and skinfolds). The research assistant who performed the measurements was blinded for group assignment. Secondary outcome measures were the children’s dietary behavior and physical activity level, parenting practices, parental feeding style, parenting style, and parental self-efficacy. Outcome measures were assessed at baseline and 4 months (short-term) and 12 months (long-term) after baseline. Multilevel multiple regression analyses were conducted to determine the effect of the intervention on primary and secondary outcome measures. Results No intervention effects were found on children’s body composition. Analyses of secondary outcomes showed positive short-term intervention effects on children’s soft-drink consumption and parental responsibility regarding physical activity, encouragement to eat, psychological control, and efficacy and satisfaction with parenting. Longer-term intervention effects were found on parent’s report of children’s time spent on sedentary behavior and playing outside, parental monitoring food intake, and responsibility regarding nutrition. Conclusion Although the Lifestyle Triple P intervention showed positive effects on some parent reported child behaviors and parenting measures, no effects were visible on children’s body composition or objectively measured physical activity. Several adjustments of the intervention content are recommended, for example including a booster session. Trial Registration Nederlands Trial Register NTR 2555 PMID:25849523

An economic evaluation based on a randomized placebo-controlled trial of varenicline in smokers with cardiovascular disease: results for Belgium, Spain, Portugal, and Italy.

PubMed

Wilson, Koo; Hettle, Robert; Marbaix, Sophie; Diaz Cerezo, Silvia; Ines, Monica; Santoni, Laura; Annemans, Lieven; Prignot, Jacques; Lopez de Sa, Esteban

2012-10-01

An estimated 17.2% of patients continue to smoke following diagnosis of cardiovascular disease (CVD). To reduce the risk of further morbidity or mortality in cardiovascular patients, smoking cessation has been shown to reduce the risk of mortality by 36% and myocardial infarction by 32%. The objective of this study was to evaluate the long-term health and economic consequences of smoking cessation in patients with CVD. Results of a randomized clinical trial comparing varenicline plus counselling vs. placebo plus counselling were extrapolated using a Markov model to simulate the lifetime costs and health consequences of smoking cessation in patients with stable CVD. For the base case, we considered a payer's perspective including direct costs attributed to the healthcare provider, measuring cumulative life years (LY) and quality adjusted life (QALY) years as outcome measures. Secondary analyses were conducted from a societal perspective, evaluating lost productivity due to premature mortality. Sensitivity and subgroup analyses were also undertaken. Results were analysed for Belgium, Spain, Portugal, and Italy. Varenicline plus counselling was associated with a gain in LY and QALY across all countries; relative to placebo plus counselling. From a payer's perspective, incremental cost effectiveness ratios were € 6120 (Belgium), € 5151 (Spain), € 5357 (Portugal), and € 5433 (Italy) per QALY gained. From a societal perspective, varenicline in addition to counselling was less costly than placebo and counselling in all cases. Sensitivity analyses showed little sensitivity in outcomes to model assumptions or uncertainty in model parameters. Varenicline in addition to counselling is cost-effective compared to placebo and counselling in smokers with CVD.

Design of the Economic Evaluation for the Interventional Management of Stroke (III) Trial

PubMed Central

Mauldin, Patrick D.; Simpson, Kit N.; Palesch, Yuko Y.; Spilker, Judy S.; Hill, Michael D.; Khatri, Pooja; Broderick, Joseph P.

2011-01-01

SUMMARY Rationale Stroke is a common and costly condition where an effective early reatment may be expected to affect patients’ future quality of life, the cost of acute medical treatment, and the cost of rehabilitation and any supportive care needed for their remaining lifetime. To assist in informing discussions on early adoption of potential treatments, economic analyses should accompany investigations that seek to improve outcomes for stroke patients. Aims The primary aim is to assess whether IV/IA rt-PA therapy is cost-effective at 3 months compared to IV rt-PA, and provides cost-savings or is cost-neutral by 12 months. Design Cost-effectiveness of the two treatment arms will be measured at months 3, 6, 9, and 12. Cost-effectiveness will be calculated using 1) standard cost-effectiveness methodology (Incremental Cost-Effectiveness Ratios), and 2) an econometric model to assess multiple outcome measures while controlling for multiple subject and treatment-related factors that are known to affect both outcomes and costs. Study Outcomes Total cost for the initial hospitalization of treating stroke subjects randomized to either IV/IA or IV rt-PA treatment arms will be measured, as will differences in types of resource utilization over 12 months between the two arms of the trial. Quality-of-life data (EuroQol EQ-5D) will be collected over a 12-month period and quality adjusted life years (QALYs) will be used as a morbidity-adjusted measure of effectiveness. Subgroup analyses will include dichotomized NIH Stroke Scale (<20, ≥20), country, time between onset and randomization, and IA devices. PMID:18706008

Effects of uric acid-lowering therapy on the progression of chronic kidney disease: a systematic review and meta-analysis.

PubMed

Liu, Xuemei; Zhai, Tingting; Ma, Ruixia; Luo, Congjuan; Wang, Huifang; Liu, Liqiu

2018-11-01

Whether uric acid levels were associated with the progression of chronic kidney disease (CKD) remained controversial. This meta-analysis was aimed to assess the effect of lowering serum uric acid therapy on the progression of CKD to clarify the role of uric acid in the progression of CKD indirectly. Pubmed, Embase, the Cochrane library, CBM were searched for randomized controlled trials (RCTs) that assessed the efficiency of lowering serum uric acid therapy on the progression of CKD without language restriction. Summary estimates of weighted mean differences (WMDs) and relative risk (RR) were obtained by using random-effect or fixed-effect models. Sensitivity analyses were performed to identify the source of heterogeneity. A total of 12 randomized controlled trials with 832 CKD participants were included in the analysis. Pooled estimate for eGFR was in favor of lowering serum uric acid therapy with a mean difference (MD) of 3.88 ml/min/1.73 m 2 , 95% CI 1.26-6.49 ml/min/1.73 m 2 , p = .004 and this was consistent with results for serum creatinine. The risk of worsening of kidney function or ESRD or death was significantly decreased in the treatment group compared to the control group (RR 0.39, 95% CI 0.28-0.52, p< .01). Uric acid-lowering therapy may be effective in retarding the progression of CKD. Further randomized controlled trials should be performed to confirm the effect of lowering serum uric acid therapy on the progression of CKD.

The acute effects of grape polyphenols supplementation on endothelial function in adults: meta-analyses of controlled trials.

PubMed

Li, Shao-Hua; Tian, Hong-Bo; Zhao, Hong-Jin; Chen, Liang-Hua; Cui, Lian-Qun

2013-01-01

The acute effects of grape polyphenols on endothelial function in adults are inconsistent. Here, we performed meta-analyses to determine these acute effects as measured by flow-mediated dilation (FMD). Trials were searched in PubMed, Embase and the Cochrane Library database. Summary estimates of weighted mean differences (WMDs) and 95% CIs were obtained by using random-effects models. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. The protocol details of our meta-analysis have been submitted to the PROSPERO register and our registration number is CRD42013004157. Nine studies were included in the present meta-analyses. The results showed that the FMD level was significantly increased in the initial 120 min after intake of grape polyphenols as compared with controls. Meta-regression and subgroup analyses were performed and showed that a health status was the main effect modifier of the significant heterogeneity. Subgroups indicated that intake of grape polyphenols could significantly increase FMD in healthy subjects, and the increased FMD appeared to be more obviously in subjects with high cardiovascular risk factors. Moreover, the peak effect of grape polyphenols on FMD in healthy subjects was found 30 min after ingestion, which was different from the effect in subjects with high cardiovascular risk factors, in whom the peak effect was found 60 min after ingestion. Endothelial function can be significantly improved in healthy adults in the initial 2 h after intake of grape polyphenols. The acute effect of grape polyphenols on endothelial function may be more significant but the peak effect is delayed in subjects with a smoking history or coronary heart disease as compared with the healthy subjects.

The Acute Effects of Grape Polyphenols Supplementation on Endothelial Function in Adults: Meta-Analyses of Controlled Trials

PubMed Central

Li, Shao-Hua; Tian, Hong-Bo; Zhao, Hong-Jin; Chen, Liang-Hua; Cui, Lian-Qun

2013-01-01

Background The acute effects of grape polyphenols on endothelial function in adults are inconsistent. Here, we performed meta-analyses to determine these acute effects as measured by flow-mediated dilation (FMD). Methods Trials were searched in PubMed, Embase and the Cochrane Library database. Summary estimates of weighted mean differences (WMDs) and 95% CIs were obtained by using random-effects models. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. The protocol details of our meta-analysis have been submitted to the PROSPERO register and our registration number is CRD42013004157. Results Nine studies were included in the present meta-analyses. The results showed that the FMD level was significantly increased in the initial 120 min after intake of grape polyphenols as compared with controls. Meta-regression and subgroup analyses were performed and showed that a health status was the main effect modifier of the significant heterogeneity. Subgroups indicated that intake of grape polyphenols could significantly increase FMD in healthy subjects, and the increased FMD appeared to be more obviously in subjects with high cardiovascular risk factors. Moreover, the peak effect of grape polyphenols on FMD in healthy subjects was found 30 min after ingestion, which was different from the effect in subjects with high cardiovascular risk factors, in whom the peak effect was found 60 min after ingestion. Conclusions Endothelial function can be significantly improved in healthy adults in the initial 2 h after intake of grape polyphenols. The acute effect of grape polyphenols on endothelial function may be more significant but the peak effect is delayed in subjects with a smoking history or coronary heart disease as compared with the healthy subjects. PMID:23894543

Treatment effect expressed as the novel Delay of Event measure is associated with high willingness to initiate preventive treatment - A randomized survey experiment comparing effect measures.

PubMed

Berglund, Erik; Westerling, Ragnar; Sundström, Johan; Lytsy, Per

2016-12-01

This study aimed to investigate patients' willingness to initiate a preventive treatment and compared two established effect measures to the newly developed Delay of Events (DoE) measure that expresses treatment effect as a gain in event-free time. In this cross-sectional, randomized survey experiment in the general Swedish population,1079 respondents (response rate 60.9%) were asked to consider a preventive cardiovascular treatment. Respondents were randomly allocated to one of three effect descriptions: DoE, relative risk reduction (RRR), or absolute risk reduction (ARR). Univariate and multivariate analyses were performed investigating willingness to initiate treatment, views on treatment benefit, motivation and importance to adhere and willingness to pay for treatment. Eighty-one percent were willing to take the medication when the effect was described as DoE, 83.0% when it was described as RRR and 62.8% when it was described as ARR. DoE and RRR was further associated with positive views on treatment benefit, motivation, importance to adhere and WTP. Presenting treatment effect as DoE or RRR was associated with a high willingness to initiate treatment. An approach based on the novel time-based measure DoE may be of value in clinical communication and shared decision making. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Systematic review of physiotherapy interventions to improve gross motor capacity and performance in children and adolescents with an acquired brain injury.

PubMed

Baque, Emmah; Sakzewski, Leanne; Barber, Lee; Boyd, Roslyn N

2016-01-01

To systematically review the efficacy of physiotherapy interventions to improve gross motor capacity, performance and societal participation in children aged 5-17 years with an acquired brain injury (ABI). Randomized and non-randomized controlled trials, cohort, case series, case-control and case studies were included and classified according to grades of evidence. Methodological quality of studies was assessed using the Downs and Black (D&B) scale and quantitative data was analysed using effect sizes. Two home-based studies investigated functional strength training (one randomized controlled trial, n = 20, level 2b, D&B = 16/32 and one non-randomized self-control study, n = 19, level 4, D&B = 15/32). Four studies evaluated virtual reality including: one pilot study, n = 50, level 4, D&B = 22/32; one single-subject, non-concurrent, randomized multiple baseline study, n = 3, level 4, D&B = 15/32; one case series study, n = 2, level 4, D&B = 15/32; one case study, n = 1, level 4, D&B = 15/32. Effect sizes for the randomized controlled trial ranged between 0.30-1.29 for the Functional Reach and Timed Up and Go outcome measures. There is preliminary evidence to support the efficacy of physiotherapy interventions to improve gross motor outcomes in children with an ABI. Both functional strength training and virtual-reality based therapy are potential treatment options for clinicians to prescribe in either home or clinical settings.

The Performance of the Date-Randomization Test in Phylogenetic Analyses of Time-Structured Virus Data.

PubMed

Duchêne, Sebastián; Duchêne, David; Holmes, Edward C; Ho, Simon Y W

2015-07-01

Rates and timescales of viral evolution can be estimated using phylogenetic analyses of time-structured molecular sequences. This involves the use of molecular-clock methods, calibrated by the sampling times of the viral sequences. However, the spread of these sampling times is not always sufficient to allow the substitution rate to be estimated accurately. We conducted Bayesian phylogenetic analyses of simulated virus data to evaluate the performance of the date-randomization test, which is sometimes used to investigate whether time-structured data sets have temporal signal. An estimate of the substitution rate passes this test if its mean does not fall within the 95% credible intervals of rate estimates obtained using replicate data sets in which the sampling times have been randomized. We find that the test sometimes fails to detect rate estimates from data with no temporal signal. This error can be minimized by using a more conservative criterion, whereby the 95% credible interval of the estimate with correct sampling times should not overlap with those obtained with randomized sampling times. We also investigated the behavior of the test when the sampling times are not uniformly distributed throughout the tree, which sometimes occurs in empirical data sets. The test performs poorly in these circumstances, such that a modification to the randomization scheme is needed. Finally, we illustrate the behavior of the test in analyses of nucleotide sequences of cereal yellow dwarf virus. Our results validate the use of the date-randomization test and allow us to propose guidelines for interpretation of its results. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Local anaesthetic infiltration for the rubber band ligation of early symptomatic haemorrhoids: a systematic review and meta-analysis.

PubMed

Sajid, M S; Bhatti, M I; Caswell, J; Sains, P; Baig, M K

2015-03-01

The objective of this article is to systematically analyse the randomized, controlled trials evaluating the effectiveness of local anaesthetic infiltration prior to the rubber band ligation of early symptomatic haemorrhoids. Published randomized, controlled trials comparing the use of local anaesthetic (LA) versus no-local anaesthetic (NLA) for the rubber band ligation of early symptomatic haemorrhoids were analysed using RevMan®, and the combined outcomes were expressed as odds ratios (OR) and standardized mean difference (SMD). Four randomized, controlled trials evaluating 387 patients were retrieved from the standard electronic databases. The risk of treatment failure (OR 0.44; 95% CI 0.07, 2.79; z = 0.87; p = 0.39) and post-procedure complications (OR 0.48; 95% CI 0.08, 2.76; z = 0.83; p = 0.41) was similar between two techniques. However, the post-procedure pain score (SMD -5.19; 95% CI -9.08, -1.30; z = 2.62; p < 0.009) was significantly lower in the group of patients undergoing rubber band ligation of haemorrhoids under local anaesthetic injection. The use of LA appears to have clinically measurable advantages over NLA in the rubber band ligation of early symptomatic haemorrhoids to lessen post-procedure pain.

Does Preoperative Radio(chemo)therapy Increase Anastomotic Leakage in Rectal Cancer Surgery? A Meta-Analysis of Randomized Controlled Trials

PubMed Central

Qin, Changjiang; Ren, Xuequn; Xu, Kaiwu; Chen, Zhihui; He, Yulong; Song, Xinming

2014-01-01

Objective. Preoperative radio(chemo)therapy (pR(C)T) appears to increase postoperative complications of rectal cancer resection, but clinical trials have reported conflicting results. The objective of this meta-analysis was performed to assess the effects of pR(C)T on anastomotic leak after rectal cancer resection. Methods. PubMed, Embase, and the Cochrane Library were searched from January 1980 to January 2014. Randomized controlled trials included all original articles reporting anastomotic leak in patients with rectal cancer, among whom some received preoperative radiotherapy or chemoradiotherapy while others did not. The analysed end-points were the anastomotic leak. Result. Seven randomized controlled trials with 3375 patients were included in the meta-analysis. 1660 forming the group undergoing preoperative radiotherapy or chemoradiotherapy versus 1715 patients undergoing without preoperative radiotherapy or chemoradiotherapy. The meta-analyses found that pR(C)T was not an independent risk factor for anastomotic leakage (OR 1.02, 95% CI 0.80–1.30; P = 0.88). Subgroups analysis was performed and the result was not altered. Conclusions. Current evidence demonstrates that pR(C)T did not increase the risk of postoperative anastomotic leak after rectal cancer resection in patients. PMID:25477955

Random Testing and Model Checking: Building a Common Framework for Nondeterministic Exploration

NASA Technical Reports Server (NTRS)

Groce, Alex; Joshi, Rajeev

2008-01-01

Two popular forms of dynamic analysis, random testing and explicit-state software model checking, are perhaps best viewed as search strategies for exploring the state spaces introduced by nondeterminism in program inputs. We present an approach that enables this nondeterminism to be expressed in the SPIN model checker's PROMELA language, and then lets users generate either model checkers or random testers from a single harness for a tested C program. Our approach makes it easy to compare model checking and random testing for models with precisely the same input ranges and probabilities and allows us to mix random testing with model checking's exhaustive exploration of non-determinism. The PROMELA language, as intended in its design, serves as a convenient notation for expressing nondeterminism and mixing random choices with nondeterministic choices. We present and discuss a comparison of random testing and model checking. The results derive from using our framework to test a C program with an effectively infinite state space, a module in JPL's next Mars rover mission. More generally, we show how the ability of the SPIN model checker to call C code can be used to extend SPIN's features, and hope to inspire others to use the same methods to implement dynamic analyses that can make use of efficient state storage, matching, and backtracking.

Publication bias in obesity treatment trials?

PubMed

Allison, D B; Faith, M S; Gorman, B S

1996-10-01

The present investigation examined the extent of publication bias (namely the tendency to publish significant findings and file away non-significant findings) within the obesity treatment literature. Quantitative literature synthesis of four published meta-analyses from the obesity treatment literature. Interventions in these studies included pharmacological, educational, child, and couples treatments. To assess publication bias, several regression procedures (for example weighted least-squares, random-effects multi-level modeling, and robust regression methods) were used to regress effect sizes onto their standard errors, or proxies thereof, within each of the four meta-analysis. A significant positive beta weight in these analyses signified publication bias. There was evidence for publication bias within two of the four published meta-analyses, such that reviews of published studies were likely to overestimate clinical efficacy. The lack of evidence for publication bias within the two other meta-analyses might have been due to insufficient statistical power rather than the absence of selection bias. As in other disciplines, publication bias appears to exist in the obesity treatment literature. Suggestions are offered for managing publication bias once identified or reducing its likelihood in the first place.

Calcium Plus Vitamin D Supplementation and Health Outcomes Five Years After Active Intervention Ended: The Women's Health Initiative

PubMed Central

Chlebowski, Rowan T.; Wactawski-Wende, Jean; Robbins, John A.; Rodabough, Rebecca J.; Chen, Zhao; Johnson, Karen C.; O'Sullivan, Mary Jo; Jackson, Rebecca D.; Manson, JoAnn E.

2013-01-01

Abstract Background Clinical outcomes of the Women's Health Initiative (WHI) calcium plus vitamin D supplementation trial have been reported during 7.0 years of active intervention. We now report outcomes 4.9 years after the intervention stopped and cumulative findings. Methods Postmenopausal women (N=36,282) were randomized; postintervention follow-up continued among 29,862 (86%) of surviving participants. Primary outcomes were hip fracture and colorectal cancer. Breast cancer, all cancers, cardiovascular disease (CVD), and total mortality were predetermined major study outcomes. Results Hip fracture incidence was comparable in the supplement and the placebo groups, postintervention hazard ratio (HR)=0.95, 95% confidence interval (95% CI: 0.78, 1.15) and overall HR=0.91 (95% CI: 0.79, 1.05). Overall, colorectal cancer incidence did not differ between randomization groups, HR=0.95 (95% CI: 0.80, 1.13). Throughout, there also was no difference in invasive breast cancer, CVD, and all-cause mortality between groups. In subgroup analyses, the invasive breast cancer effect varied by baseline vitamin D intake (p=0.03 for interaction). Women with vitamin D intakes >600 IU/d, had an increased risk of invasive breast cancer, HR=1.28 (95% CI; 1.03, 1.60). Over the entire study period, in post hoc analyses, the incidence of vertebral fractures, HR=0.87 (95% CI: 0.76, 0.98) and in situ breast cancers, HR=0.82 (95% CI: 0.68, 0.99) were lower among women randomized to supplementation. Conclusion After an average of 11 years, calcium and vitamin D supplementation did not decrease hip fracture or colorectal cancer incidence. Exploratory analyses found lower vertebral fracture and in situ breast cancer incidence in the supplement users. There was no effect on CVD or all-cause mortality. PMID:24131320