Image analysis of oronasal fistulas in cleft palate patients acquired with an intraoral camera.

PubMed

Murphy, Tania C; Willmot, Derrick R

2005-01-01

The aim of this study was to examine the clinical technique of using an intraoral camera to monitor the size of residual oronasal fistulas in cleft lip-cleft palate patients, to assess its repeatability on study casts and patients, and to compare its use with other methods. Seventeen plaster study casts of cleft palate patients with oronasal fistulas obtained from a 5-year series of 160 patients were used. For the clinical study, 13 patients presenting in a clinic prospectively over a 1-year period were imaged twice by the camera. The area of each fistula on each study cast was measured in the laboratory first using a previously described graph paper and caliper technique and second with the intraoral camera. Images were imported into a computer and subjected to image enhancement and area measurement. The camera was calibrated by imaging a standard periodontal probe within the fistula area. The measurements were repeated using a double-blind technique on randomly renumbered casts to assess the repeatability of measurement of the methods. The clinical images were randomly and blindly numbered and subjected to image enhancement and processing in the same way as for the study casts. Area measurements were computed. Statistical analysis of repeatability of measurement using a paired sample t test showed no significant difference between measurements, indicating a lack of systematic error. An intraclass correlation coefficient of 0.97 for the graph paper and 0.84 for the camera method showed acceptable random error between the repeated records for each of the two methods. The graph paper method remained slightly more repeatable. The mean fistula area of the study casts between each method was not statistically different when compared with a paired samples t test (p = 0.08). The methods were compared using the limits of agreement technique, which showed clinically acceptable repeatability. The clinical study of repeated measures showed no systematic differences when subjected to a t test (p = 0.109) and little random error with an intraclass correlation coefficient of 0.98. The fistula size seen in the clinical study ranged from 18.54 to 271.55 mm. Direct measurements subsequently taken on 13 patients in the clinic without study models showed a wide variation in the size of residual fistulas presenting in a multidisciplinary clinic. It was concluded that an intraoral camera method could be used in place of the previous graph paper method and could be developed for clinical and scientific purposes. This technique may offer advantages over the graph paper method, as it facilitates easy visualization of oronasal fistulas and objective fistulas size determination and permits easy storage of data in clinical records.

Effect of Atomoxetine on Executive Function Impairments in Adults with ADHD

ERIC Educational Resources Information Center

Brown, Thomas E.; Holdnack, James; Saylor, Keith; Adler, Lenard; Spencer, Thomas; Williams, David W.; Padival, Anoop K.; Schuh, Kory; Trzepacz, Paula T.; Kelsey, Douglas

2011-01-01

Objective: To assess the effect of atomoxetine on ADHD-related executive functions over a 6-month period using the Brown Attention-Deficit Disorder Scale (BADDS) for Adults, a normed, 40-item, self-report scale in a randomized, double-blind, placebo-controlled clinical trial. Method: In a randomized, double-blind clinical trial, adults with ADHD…

Effects of a novel method for enteral nutrition infusion involving a viscosity-regulating pectin solution: A multicenter randomized controlled trial.

PubMed

Tabei, Isao; Tsuchida, Shigeru; Akashi, Tetsuro; Ookubo, Katsuichiro; Hosoda, Satoru; Furukawa, Yoshiyuki; Tanabe, Yoshiaki; Tamura, Yoshiko

2018-02-01

The initial complications associated with infusion of enteral nutrition (EN) for clinical and nutritional care are vomiting, aspiration pneumonia, and diarrhea. There are many recommendations to prevent these complications. A novel method involving a viscosity-regulating pectin solution has been demonstrated. In Japan, this method along with the other so-called "semi-solid EN" approaches has been widely used in practice. However, there has been no randomized clinical trial to prove the efficiency and safety of a viscosity-regulating pectin solution in EN management. Therefore, we planned and initiated a multicenter randomized controlled trial to determine the efficiency and safety. This study included 34 patients from 7 medical institutions who participated. Institutional review board (IRB) approval was obtained from all participating institutions. Patients who required EN management were enrolled and randomly assigned to the viscosity regulation of enteral feeding (VREF) group and control group. The VREF group (n = 15) was managed with the addition of a viscosity-regulating pectin solution. The control group (n = 12) was managed with conventional EN administration, usually in a gradual step-up method. Daily clinical symptoms of pneumonia, fever, vomiting, and diarrhea; defecation frequency; and stool form were observed in the 2 week trial period. The dose of EN and duration of infusion were also examined. A favorable trend for clinical symptoms was noticed in the VREF group. No significant differences were observed in episodes of pneumonia, fever, vomiting, and diarrhea between the 2 groups. An apparent reduction in infusion duration and hardening of stool form were noted in the VREF group. The novel method involving a viscosity-regulating pectin solution with EN administration can be clinically performed safely and efficiently, similar to the conventional method. Moreover, there were benefits, such as improvement in stool form, a short time for EN infusion, and a reduction in vomiting episodes, with the use of the novel method. This indicates some potential advantages in the quality of life among patients receiving this novel method. Copyright © 2017 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

Perceptions of Massage Therapists Participating in a Randomized Controlled Trial

PubMed Central

Perlman, Adam; Dreusicke, Mark; Keever, Teresa; Ali, Ather

2015-01-01

Background Clinical practice and randomized trials often have disparate aims, despite involving similar interventions. Attitudes and expectancies of practitioners influence patient outcomes, and there is growing emphasis on optimizing provider–patient relationships. In this study, we evaluated the experiences of licensed massage therapists involved in a randomized controlled clinical trial using qualitative methodology. Methods Seven massage therapists who were interventionists in a randomized controlled trial participated in structured interviews approximately 30 minutes in length. Interviews focused on their experiences and perceptions regarding aspects of the clinical trial, as well as recommendations for future trials. Transcribed interviews were analyzed for emergent topics and themes using standard qualitative methods. Results Six themes emerged. Therapists discussed 1) promoting the profession of massage therapy through research, 2) mixed views on using standardized protocols, 3) challenges of sham interventions, 4) participant response to the sham intervention, 5) views on scheduling and compensation, and 6) unanticipated benefits of participating in research. Conclusions Therapists largely appreciated the opportunity to promote massage through research. They demonstrated insight and understanding of the rationale for a clinical trial adhering to a standardized protocol. Evaluating the experiences and ideas of complementary and alternative medicine practitioners provides valuable insight that is relevant for the implementation and design of randomized trials. PMID:26388961

Recruitment methods and costs for a randomized, placebo-controlled trial of chiropractic care for lumbar spinal stenosis: a single-site pilot study.

PubMed

Cambron, Jerrilyn A; Dexheimer, Jennifer M; Chang, Mabel; Cramer, Gregory D

2010-01-01

The purpose of this article is to describe the methods for recruitment in a clinical trial on chiropractic care for lumbar spinal stenosis. This randomized, placebo-controlled pilot study investigated the efficacy of different amounts of total treatment dosage over 6 weeks in 60 volunteer subjects with lumbar spinal stenosis. Subjects were recruited for this study through several media venues, focusing on successful and cost-effective strategies. Included in our efforts were radio advertising, newspaper advertising, direct mail, and various other low-cost initiatives. Of the 1211 telephone screens, 60 responders (5.0%) were randomized into the study. The most successful recruitment method was radio advertising, generating more than 64% of the calls (776 subjects). Newspaper and magazine advertising generated approximately 9% of all calls (108 subjects), and direct mail generated less than 7% (79 subjects). The total direct cost for recruitment was $40 740 or $679 per randomized patient. The costs per randomization were highest for direct mail ($995 per randomization) and lowest for newspaper/magazine advertising ($558 per randomization). Success of recruitment methods may vary based on target population and location. Planning of recruitment efforts is essential to the success of any clinical trial. Copyright 2010 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.

Role of re-screening of cervical smears in internal quality control.

PubMed Central

Baker, A; Melcher, D; Smith, R

1995-01-01

AIMS--To investigate the use of rapid re-screening as a quality control method for previously screened cervical slides; to compare this method with 10% random re-screening and clinically indicated double screening. METHODS--Between June 1990 and December 1994, 117,890 negative smears were subjected to rapid re-screening. RESULTS--This study shows that rapid re-screening detects far greater numbers of false negative cases when compared with both 10% random re-screening and clinically indicated double screening, with no additional demand on human resources. The technique also identifies variation in the performance of screening personnel as an additional benefit. CONCLUSION--Rapid re-screening is an effective method of quality control. Although less sensitive, rapid re-screening should replace 10% random re-screening and selected re-screening as greater numbers of false negative results are detected while consuming less resources. PMID:8543619

Impact of a mHealth intervention for peer health workers on AIDS care in rural Uganda: a mixed methods evaluation of a cluster-randomized trial.

PubMed

Chang, Larry W; Kagaayi, Joseph; Arem, Hannah; Nakigozi, Gertrude; Ssempijja, Victor; Serwadda, David; Quinn, Thomas C; Gray, Ronald H; Bollinger, Robert C; Reynolds, Steven J

2011-11-01

Mobile phone access in low and middle-income countries is rapidly expanding and offers an opportunity to leverage limited human resources for health. We conducted a mixed methods evaluation of a cluster-randomized trial exploratory substudy on the impact of a mHealth (mobile phone) support intervention used by community-based peer health workers (PHW) on AIDS care in rural Uganda. 29 PHWs at 10 clinics were randomized by clinic to receive the intervention or not. PHWs used phones to call and text higher level providers with patient-specific clinical information. 970 patients cared for by the PHWs were followed over a 26 month period. No significant differences were found in patients' risk of virologic failure. Qualitative analyses found improvements in patient care and logistics and broad support for the mHealth intervention among patients, clinic staff, and PHWs. Key challenges identified included variable patient phone access, privacy concerns, and phone maintenance.

Applying Active Learning to Assertion Classification of Concepts in Clinical Text

PubMed Central

Chen, Yukun; Mani, Subramani; Xu, Hua

2012-01-01

Supervised machine learning methods for clinical natural language processing (NLP) research require a large number of annotated samples, which are very expensive to build because of the involvement of physicians. Active learning, an approach that actively samples from a large pool, provides an alternative solution. Its major goal in classification is to reduce the annotation effort while maintaining the quality of the predictive model. However, few studies have investigated its uses in clinical NLP. This paper reports an application of active learning to a clinical text classification task: to determine the assertion status of clinical concepts. The annotated corpus for the assertion classification task in the 2010 i2b2/VA Clinical NLP Challenge was used in this study. We implemented several existing and newly developed active learning algorithms and assessed their uses. The outcome is reported in the global ALC score, based on the Area under the average Learning Curve of the AUC (Area Under the Curve) score. Results showed that when the same number of annotated samples was used, active learning strategies could generate better classification models (best ALC – 0.7715) than the passive learning method (random sampling) (ALC – 0.7411). Moreover, to achieve the same classification performance, active learning strategies required fewer samples than the random sampling method. For example, to achieve an AUC of 0.79, the random sampling method used 32 samples, while our best active learning algorithm required only 12 samples, a reduction of 62.5% in manual annotation effort. PMID:22127105

Cognitive Behavioral Treatment of PTSD in Residents of Battered Women's Shelters: Results of a Randomized Clinical Trial

ERIC Educational Resources Information Center

Johnson, Dawn M.; Zlotnick, Caron; Perez, Sara

2011-01-01

Objective: This study was designed to explore the acceptability, feasibility, and initial efficacy of a new shelter-based treatment for victims of intimate partner violence (IPV; i.e., Helping to Overcome PTSD through Empowerment [HOPE]). Method: A Phase I randomized clinical trial comparing HOPE (n = 35) with standard shelter services (SSS) (n =…

Does Maintenance CBT Contribute to Long-Term Treatment Response of Panic Disorder with or without Agoraphobia? A Randomized Controlled Clinical Trial

ERIC Educational Resources Information Center

White, Kamila S.; Payne, Laura A.; Gorman, Jack M.; Shear, M. Katherine; Woods, Scott W.; Saksa, John R.; Barlow, David H.

2013-01-01

Objective: We examined the possibility that maintenance cognitive behavior therapy (M-CBT) may improve the likelihood of sustained improvement and reduced relapse in a multi-site randomized controlled clinical trial of patients who met criteria for panic disorder with or without agoraphobia. Method: Participants were all patients (N = 379) who…

OARSI Clinical Trials Recommendations: Design and conduct of clinical trials of lifestyle diet and exercise interventions for osteoarthritis.

PubMed

Messier, S P; Callahan, L F; Golightly, Y M; Keefe, F J

2015-05-01

The objective was to develop a set of "best practices" for use as a primer for those interested in entering the clinical trials field for lifestyle diet and/or exercise interventions in osteoarthritis (OA), and as a set of recommendations for experienced clinical trials investigators. A subcommittee of the non-pharmacologic therapies committee of the OARSI Clinical Trials Working Group was selected by the Steering Committee to develop a set of recommended principles for non-pharmacologic diet/exercise OA randomized clinical trials. Topics were identified for inclusion by co-authors and reviewed by the subcommittee. Resources included authors' expert opinions, traditional search methods including MEDLINE (via PubMed), and previously published guidelines. Suggested steps and considerations for study methods (e.g., recruitment and enrollment of participants, study design, intervention and assessment methods) were recommended. The recommendations set forth in this paper provide a guide from which a research group can design a lifestyle diet/exercise randomized clinical trial in patients with OA. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

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

Differences Between Dual-Method and Non–Dual-Method Protection Use in a Sample of Young African American Women Residing in the Southeastern United States

PubMed Central

Sales, Jessica M.; Latham, Teaniese P.; DiClemente, Ralph J.; Rose, Eve

2013-01-01

Objectives To characterize dual-method protection users and report the prevalence of dual-method use among young adult African American women residing in the Southeastern United States. Design Analysis of baseline data from a randomized controlled trial. Setting A clinic-based sample of young women enrolled in a randomized trial of a human immunodeficiency virus (HIV)–prevention program in Atlanta, Georgia, from June 2005 to June 2007. Participants African American women aged 14 to 20 years who reported unprotected sexual activity in the past 6months. Of the eligible adolescents, 94% (N=701) were enrolled in the study and completed baseline assessments. Outcome Measures Dual-method protection use as well as sociodemographic, individual-level, interpersonal-level, and community-level factors and interpersonal communication skills. Only data from the baseline assessment, before randomization, were used for the analysis. Results A total of 102 participants (14.6%) were classified as dual-method protection users. After controlling for age and clinic, significant differences between dual-method users and non–dual-method users were found for impulsivity, self-esteem, social support, relationship style, partner communication self-efficacy, and fear of condom negotiation. Conclusions Dual-method protection use is low. Identification of factors that differentiate dual-method users from non–dual-method users at the individual, interpersonal, and community levels in this young African American sample suggests that HIV, sexually transmitted disease, and unintended pregnancy risk–reduction programs should address factors at each level, not simply the individual level, and that this may involve structural and/or clinical counseling practice changes in clinics that serve young women, to optimally facilitate dual-method protection use among young African American women in the Southeastern United States. PMID:21135341

A comparative study of restricted randomization procedures for multiarm trials with equal or unequal treatment allocation ratios.

PubMed

Ryeznik, Yevgen; Sverdlov, Oleksandr

2018-06-04

Randomization designs for multiarm clinical trials are increasingly used in practice, especially in phase II dose-ranging studies. Many new methods have been proposed in the literature; however, there is lack of systematic, head-to-head comparison of the competing designs. In this paper, we systematically investigate statistical properties of various restricted randomization procedures for multiarm trials with fixed and possibly unequal allocation ratios. The design operating characteristics include measures of allocation balance, randomness of treatment assignments, variations in the allocation ratio, and statistical characteristics such as type I error rate and power. The results from the current paper should help clinical investigators select an appropriate randomization procedure for their clinical trial. We also provide a web-based R shiny application that can be used to reproduce all results in this paper and run simulations under additional user-defined experimental scenarios. Copyright © 2018 John Wiley & Sons, Ltd.

Sensitivity analysis for missing dichotomous outcome data in multi-visit randomized clinical trial with randomization-based covariance adjustment.

PubMed

Li, Siying; Koch, Gary G; Preisser, John S; Lam, Diana; Sanchez-Kam, Matilde

2017-01-01

Dichotomous endpoints in clinical trials have only two possible outcomes, either directly or via categorization of an ordinal or continuous observation. It is common to have missing data for one or more visits during a multi-visit study. This paper presents a closed form method for sensitivity analysis of a randomized multi-visit clinical trial that possibly has missing not at random (MNAR) dichotomous data. Counts of missing data are redistributed to the favorable and unfavorable outcomes mathematically to address possibly informative missing data. Adjusted proportion estimates and their closed form covariance matrix estimates are provided. Treatment comparisons over time are addressed with Mantel-Haenszel adjustment for a stratification factor and/or randomization-based adjustment for baseline covariables. The application of such sensitivity analyses is illustrated with an example. An appendix outlines an extension of the methodology to ordinal endpoints.

A Randomized Prospective Trial Comparing Paravertebral Block and General Anesthesia for Operative Treatment of Breast Cancer

DTIC Science & Technology

2001-10-01

block the anesthetic of choice for operative treatment of breast cancer. To test this hypothesis we proposed a prospective randomized clinical trial ...coordinators. Months 4-6. Status: Complete The study’s existing part-time Clinical Trial Coordinator, Mr. John Arbo, was enlisted full-time in June...of full-time Clinical Trial Coordinator for Mount Sinai. ■ Poster presentation by Mount Sinai staff of study goals and methods at a Department of

Personalized Risk Prediction in Clinical Oncology Research: Applications and Practical Issues Using Survival Trees and Random Forests.

PubMed

Hu, Chen; Steingrimsson, Jon Arni

2018-01-01

A crucial component of making individualized treatment decisions is to accurately predict each patient's disease risk. In clinical oncology, disease risks are often measured through time-to-event data, such as overall survival and progression/recurrence-free survival, and are often subject to censoring. Risk prediction models based on recursive partitioning methods are becoming increasingly popular largely due to their ability to handle nonlinear relationships, higher-order interactions, and/or high-dimensional covariates. The most popular recursive partitioning methods are versions of the Classification and Regression Tree (CART) algorithm, which builds a simple interpretable tree structured model. With the aim of increasing prediction accuracy, the random forest algorithm averages multiple CART trees, creating a flexible risk prediction model. Risk prediction models used in clinical oncology commonly use both traditional demographic and tumor pathological factors as well as high-dimensional genetic markers and treatment parameters from multimodality treatments. In this article, we describe the most commonly used extensions of the CART and random forest algorithms to right-censored outcomes. We focus on how they differ from the methods for noncensored outcomes, and how the different splitting rules and methods for cost-complexity pruning impact these algorithms. We demonstrate these algorithms by analyzing a randomized Phase III clinical trial of breast cancer. We also conduct Monte Carlo simulations to compare the prediction accuracy of survival forests with more commonly used regression models under various scenarios. These simulation studies aim to evaluate how sensitive the prediction accuracy is to the underlying model specifications, the choice of tuning parameters, and the degrees of missing covariates.

Meta-analysis in clinical trials revisited.

PubMed

DerSimonian, Rebecca; Laird, Nan

2015-11-01

In this paper, we revisit a 1986 article we published in this Journal, Meta-Analysis in Clinical Trials, where we introduced a random-effects model to summarize the evidence about treatment efficacy from a number of related clinical trials. Because of its simplicity and ease of implementation, our approach has been widely used (with more than 12,000 citations to date) and the "DerSimonian and Laird method" is now often referred to as the 'standard approach' or a 'popular' method for meta-analysis in medical and clinical research. The method is especially useful for providing an overall effect estimate and for characterizing the heterogeneity of effects across a series of studies. Here, we review the background that led to the original 1986 article, briefly describe the random-effects approach for meta-analysis, explore its use in various settings and trends over time and recommend a refinement to the method using a robust variance estimator for testing overall effect. We conclude with a discussion of repurposing the method for Big Data meta-analysis and Genome Wide Association Studies for studying the importance of genetic variants in complex diseases. Published by Elsevier Inc.

Changes in energy expenditure in preterm infants during weaning: a randomized comparison of two weaning methods from an incubator.

PubMed

Weintraub, Valentin; Mimouni, Francis B; Dollberg, Shaul

2007-03-01

We aimed to compare resting energy expenditure (REE) of infants exposed to either one of two weaning methods and to confirm the increase in REE during weaning from incubator. The study was a prospective randomized clinical trial of weaning preterm infants using either of two methods. REE was measured at baseline and 6, 23, 30, and 47 h, using indirect calorimetry. At measurement, infants were clinically and thermally stable, asleep, 2 h after feeding. Forty-two patients were randomized to "open incubator" (n = 23) or "warming bassinet" (n = 19). The groups did not differ in baseline clinical characteristics. REE increased significantly in both groups within 23 h, and remained stable at 30 and 47 h. At 6 and 23 h, the incubator group had significantly higher increase in REE than the warming bassinet group. By 30 h and at 47 h post-weaning, the REE of both groups became similar. In conclusion, REE increases significantly at weaning from incubator. The warming bassinet delays the increase in REE observed when infants are weaned using a turned off incubator. Whether one method is superior to the other in terms of thermic stress cannot be determined from this study.

Using pilot data to size a two-arm randomized trial to find a nearly optimal personalized treatment strategy.

PubMed

Laber, Eric B; Zhao, Ying-Qi; Regh, Todd; Davidian, Marie; Tsiatis, Anastasios; Stanford, Joseph B; Zeng, Donglin; Song, Rui; Kosorok, Michael R

2016-04-15

A personalized treatment strategy formalizes evidence-based treatment selection by mapping patient information to a recommended treatment. Personalized treatment strategies can produce better patient outcomes while reducing cost and treatment burden. Thus, among clinical and intervention scientists, there is a growing interest in conducting randomized clinical trials when one of the primary aims is estimation of a personalized treatment strategy. However, at present, there are no appropriate sample size formulae to assist in the design of such a trial. Furthermore, because the sampling distribution of the estimated outcome under an estimated optimal treatment strategy can be highly sensitive to small perturbations in the underlying generative model, sample size calculations based on standard (uncorrected) asymptotic approximations or computer simulations may not be reliable. We offer a simple and robust method for powering a single stage, two-armed randomized clinical trial when the primary aim is estimating the optimal single stage personalized treatment strategy. The proposed method is based on inverting a plugin projection confidence interval and is thereby regular and robust to small perturbations of the underlying generative model. The proposed method requires elicitation of two clinically meaningful parameters from clinical scientists and uses data from a small pilot study to estimate nuisance parameters, which are not easily elicited. The method performs well in simulated experiments and is illustrated using data from a pilot study of time to conception and fertility awareness. Copyright © 2015 John Wiley & Sons, Ltd.

Monolingual or Bilingual Intervention for Primary Language Impairment? A Randomized Control Trial

ERIC Educational Resources Information Center

Thordardottir, Elin; Cloutier, Geneviève; Ménard, Suzanne; Pelland-Blais, Elaine; Rvachew, Susan

2015-01-01

Purpose: This study investigated the clinical effectiveness of monolingual versus bilingual language intervention, the latter involving speech-language pathologist-parent collaboration. The study focuses on methods that are currently being recommended and that are feasible within current clinical contexts. Method: Bilingual children with primary…

Machine learning algorithms for the creation of clinical healthcare enterprise systems

NASA Astrophysics Data System (ADS)

Mandal, Indrajit

2017-10-01

Clinical recommender systems are increasingly becoming popular for improving modern healthcare systems. Enterprise systems are persuasively used for creating effective nurse care plans to provide nurse training, clinical recommendations and clinical quality control. A novel design of a reliable clinical recommender system based on multiple classifier system (MCS) is implemented. A hybrid machine learning (ML) ensemble based on random subspace method and random forest is presented. The performance accuracy and robustness of proposed enterprise architecture are quantitatively estimated to be above 99% and 97%, respectively (above 95% confidence interval). The study then extends to experimental analysis of the clinical recommender system with respect to the noisy data environment. The ranking of items in nurse care plan is demonstrated using machine learning algorithms (MLAs) to overcome the drawback of the traditional association rule method. The promising experimental results are compared against the sate-of-the-art approaches to highlight the advancement in recommendation technology. The proposed recommender system is experimentally validated using five benchmark clinical data to reinforce the research findings.

Electronic Cigarettes for Smoking Cessation.

PubMed

Orellana-Barrios, Menfil A; Payne, Drew; Medrano-Juarez, Rita M; Yang, Shengping; Nugent, Kenneth

2016-10-01

The use of electronic cigarettes (e-cigarettes) is increasing, but their use as a smoking-cessation aid is controversial. The reporting of e-cigarette studies on cessation is variable and inconsistent. To date, only 1 randomized clinical trial has included an arm with other cessation methods (nicotine patches). The cessation rates for available clinical trials are difficult to compare given differing follow-up periods and broad ranges (4% at 12 months with non-nicotine e-cigarettes to 68% at 4 weeks with concomitant nicotine e-cigarettes and other cessation methods). The average combined abstinence rate for included prospective studies was 29.1% (combination of 6-18 months׳ rates). There are few comparable clinical trials and prospective studies related to e-cigarettes use for smoking cessation, despite an increasing number of citations. Larger randomized clinical trials are essential to determine whether e-cigarettes are effective smoking-cessation devices. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Missing data and multiple imputation in clinical epidemiological research.

PubMed

Pedersen, Alma B; Mikkelsen, Ellen M; Cronin-Fenton, Deirdre; Kristensen, Nickolaj R; Pham, Tra My; Pedersen, Lars; Petersen, Irene

2017-01-01

Missing data are ubiquitous in clinical epidemiological research. Individuals with missing data may differ from those with no missing data in terms of the outcome of interest and prognosis in general. Missing data are often categorized into the following three types: missing completely at random (MCAR), missing at random (MAR), and missing not at random (MNAR). In clinical epidemiological research, missing data are seldom MCAR. Missing data can constitute considerable challenges in the analyses and interpretation of results and can potentially weaken the validity of results and conclusions. A number of methods have been developed for dealing with missing data. These include complete-case analyses, missing indicator method, single value imputation, and sensitivity analyses incorporating worst-case and best-case scenarios. If applied under the MCAR assumption, some of these methods can provide unbiased but often less precise estimates. Multiple imputation is an alternative method to deal with missing data, which accounts for the uncertainty associated with missing data. Multiple imputation is implemented in most statistical software under the MAR assumption and provides unbiased and valid estimates of associations based on information from the available data. The method affects not only the coefficient estimates for variables with missing data but also the estimates for other variables with no missing data.

Missing data and multiple imputation in clinical epidemiological research

PubMed Central

Pedersen, Alma B; Mikkelsen, Ellen M; Cronin-Fenton, Deirdre; Kristensen, Nickolaj R; Pham, Tra My; Pedersen, Lars; Petersen, Irene

2017-01-01

Missing data are ubiquitous in clinical epidemiological research. Individuals with missing data may differ from those with no missing data in terms of the outcome of interest and prognosis in general. Missing data are often categorized into the following three types: missing completely at random (MCAR), missing at random (MAR), and missing not at random (MNAR). In clinical epidemiological research, missing data are seldom MCAR. Missing data can constitute considerable challenges in the analyses and interpretation of results and can potentially weaken the validity of results and conclusions. A number of methods have been developed for dealing with missing data. These include complete-case analyses, missing indicator method, single value imputation, and sensitivity analyses incorporating worst-case and best-case scenarios. If applied under the MCAR assumption, some of these methods can provide unbiased but often less precise estimates. Multiple imputation is an alternative method to deal with missing data, which accounts for the uncertainty associated with missing data. Multiple imputation is implemented in most statistical software under the MAR assumption and provides unbiased and valid estimates of associations based on information from the available data. The method affects not only the coefficient estimates for variables with missing data but also the estimates for other variables with no missing data. PMID:28352203

Causal inference from observational data.

PubMed

Listl, Stefan; Jürges, Hendrik; Watt, Richard G

2016-10-01

Randomized controlled trials have long been considered the 'gold standard' for causal inference in clinical research. In the absence of randomized experiments, identification of reliable intervention points to improve oral health is often perceived as a challenge. But other fields of science, such as social science, have always been challenged by ethical constraints to conducting randomized controlled trials. Methods have been established to make causal inference using observational data, and these methods are becoming increasingly relevant in clinical medicine, health policy and public health research. This study provides an overview of state-of-the-art methods specifically designed for causal inference in observational data, including difference-in-differences (DiD) analyses, instrumental variables (IV), regression discontinuity designs (RDD) and fixed-effects panel data analysis. The described methods may be particularly useful in dental research, not least because of the increasing availability of routinely collected administrative data and electronic health records ('big data'). © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Digital transillumination in caries detection versus radiographic and clinical methods: an in-vivo study

PubMed Central

Lara-Capi, Cynthia; Lingström, Peter; Lai, Gianfranco; Cocco, Fabio; Simark-Mattsson, Charlotte; Campus, Guglielmo

2017-01-01

Objectives: This article aimed to evaluate: (a) the agreement between a near-infrared light transillumination device and clinical and radiographic examinations in caries lesion detection and (b) the reliability of images captured by the transillumination device. Methods: Two calibrated examiners evaluated the caries status in premolars and molars on 52 randomly selected subjects by comparing the transillumination device with a clinical examination for the occlusal surfaces and by comparing the transillumination device with a radiographic examination (bitewing radiographs) for the approximal surfaces. Forty-eight trained dental hygienists evaluated and reevaluated 30 randomly selected images 1-month later. Results: A high concordance between transillumination method and clinical examination (kappa = 0.99) was detected for occlusal caries lesions, while for approximal surfaces, the transillumination device identified a higher number of lesions with respect to bitewing (kappa = 0.91). At the dentinal level, the two methods identified the same number of caries lesions (kappa = 1), whereas more approximal lesions were recorded using the transillumination device in the enamel (kappa = 0.24). The intraexaminer reliability was substantial/almost perfect in 59.4% of the participants. Conclusions: The transillumination method showed a high concordance compared with traditional methods (clinical examination and bitewing radiographs). Caries detection reliability using the transillumination device images showed a high intraexaminer agreement. Transillumination showed to be a reliable method and as effective as traditional methods in caries detection. PMID:28191797

Assessment of Registration Information on Methodological Design of Acupuncture RCTs: A Review of 453 Registration Records Retrieved from WHO International Clinical Trials Registry Platform

PubMed Central

Gu, Jing; Wang, Qi; Wang, Xiaogang; Li, Hailong; Gu, Mei; Ming, Haixia; Dong, Xiaoli; Yang, Kehu; Wu, Hongyan

2014-01-01

Background. This review provides the first methodological information assessment of protocol of acupuncture RCTs registered in WHO International Clinical Trials Registry Platform (ICTRP). Methods. All records of acupuncture RCTs registered in the ICTRP have been collected. The methodological design assessment involved whether the randomization methods, allocation concealment, and blinding were adequate or not based on the information of registration records (protocols of acupuncture RCTs). Results. A total of 453 records, found in 11 registries, were examined. Methodological details were insufficient in registration records; there were 76.4%, 89.0%, and 21.4% records that did not provide information on randomization methods, allocation concealment, and blinding respectively. The proportions of adequate randomization methods, allocation concealment, and blinding were only 107 (23.6%), 48 (10.6%), and 210 (46.4%), respectively. The methodological design improved year by year, especially after 2007. Additionally, methodology of RCTs with ethics approval was clearly superior to those without ethics approval and different among registries. Conclusions. The overall methodological design based on registration records of acupuncture RCTs is not very well but improved year by year. The insufficient information on randomization methods, allocation concealment, and blinding maybe due to the relevant description is not taken seriously in acupuncture RCTs' registration. PMID:24688591

Assessment of Registration Information on Methodological Design of Acupuncture RCTs: A Review of 453 Registration Records Retrieved from WHO International Clinical Trials Registry Platform.

PubMed

Gu, Jing; Wang, Qi; Wang, Xiaogang; Li, Hailong; Gu, Mei; Ming, Haixia; Dong, Xiaoli; Yang, Kehu; Wu, Hongyan

2014-01-01

Background. This review provides the first methodological information assessment of protocol of acupuncture RCTs registered in WHO International Clinical Trials Registry Platform (ICTRP). Methods. All records of acupuncture RCTs registered in the ICTRP have been collected. The methodological design assessment involved whether the randomization methods, allocation concealment, and blinding were adequate or not based on the information of registration records (protocols of acupuncture RCTs). Results. A total of 453 records, found in 11 registries, were examined. Methodological details were insufficient in registration records; there were 76.4%, 89.0%, and 21.4% records that did not provide information on randomization methods, allocation concealment, and blinding respectively. The proportions of adequate randomization methods, allocation concealment, and blinding were only 107 (23.6%), 48 (10.6%), and 210 (46.4%), respectively. The methodological design improved year by year, especially after 2007. Additionally, methodology of RCTs with ethics approval was clearly superior to those without ethics approval and different among registries. Conclusions. The overall methodological design based on registration records of acupuncture RCTs is not very well but improved year by year. The insufficient information on randomization methods, allocation concealment, and blinding maybe due to the relevant description is not taken seriously in acupuncture RCTs' registration.

Analysis of causality from observational studies and its application in clinical research in Intensive Care Medicine.

PubMed

Coscia Requena, C; Muriel, A; Peñuelas, O

2018-02-28

Random allocation of treatment or intervention is the key feature of clinical trials and divides patients into treatment groups that are approximately balanced for baseline, and therefore comparable covariates except for the variable treatment of the study. However, in observational studies, where treatment allocation is not random, patients in the treatment and control groups often differ in covariates that are related to intervention variables. These imbalances in covariates can lead to biased estimates of the treatment effect. However, randomized clinical trials are sometimes not feasible for ethical, logistical, economic or other reasons. To resolve these situations, interest in the field of clinical research has grown in designing studies that are most similar to randomized experiments using observational (i.e. non-random) data. Observational studies using propensity score analysis methods have been increasing in the scientific papers of Intensive Care. Propensity score analyses attempt to control for confounding in non-experimental studies by adjusting for the likelihood that a given patient is exposed. However, studies with propensity indexes may be confusing, and intensivists are not familiar with this methodology and may not fully understand the importance of this technique. The objectives of this review are: to describe the fundamentals of propensity index methods; to present the techniques to adequately evaluate propensity index models; to discuss the advantages and disadvantages of these techniques. Copyright © 2018 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Meta-Analysis in Clinical Trials Revisited

PubMed Central

Laird, Nan

2015-01-01

In this paper, we revisit a 1986 article we published in this Journal, Meta-Analysis in Clinical Trials, where we introduced a random-effect model to summarize the evidence about treatment efficacy from a number of related clinical trials. Because of its simplicity and ease of implementation, our approach has been widely used (with more than 12,000 citations to date) and the “DerSimonian and Laird method” is now often referred to as the ‘standard approach’ or a ‘popular’ method for meta-analysis in medical and clinical research. The method is especially useful for providing an overall effect estimate and for characterizing the heterogeneity of effects across a series of studies. Here, we review the background that led to the original 1986 article, briefly describe the random-effects approach for meta-analysis, explore its use in various settings and trends over time and recommend a refinement to the method using a robust variance estimator for testing overall effect. We conclude with a discussion of repurposing the method for Big Data meta-analysis and Genome Wide Association Studies for studying the importance of genetic variants in complex diseases. PMID:26343745

Development and testing of an iOS waiting room "app" for contraceptive counseling in a Title X family planning clinic.

PubMed

Gilliam, Melissa L; Martins, Summer L; Bartlett, Emily; Mistretta, Stephanie Q; Holl, Jane L

2014-11-01

Long-acting reversible contraceptive (LARC) methods, such as the intrauterine device and implant, are highly effective but used by less than 10% of US women. The objective of our study was to improve LARC interest by enhancing clinic counseling. A quality improvement methodology was used to evaluate intrauterine device service delivery in 3 Chicago Title X clinics. To address identified barriers, we developed a theory-based iOS application (app) for patients to use in the clinic waiting room using human-centered design. The final prototype was tested in a randomized controlled trial in a Title X clinic with sexually active females (79% African American) under age 30 years. Our sample of 60 was chosen to detect an increase from 10% (baseline) to 45% (app intervention) in the proportion of patients expressing interest in discussing a LARC method during their clinic visit with 80% power and two-sided α = 0.05. After completing demographic and baseline knowledge questionnaires, participants were randomized 1:1 to intervention (app) or standard care arms. App users also completed a posttest. Our primary outcome was expressed interest in discussing a LARC method during the clinic visit. Secondary outcomes were contraceptive knowledge and LARC selection. App testers (n = 17) preferred interactive, visually appealing design and video testimonials. In the pilot randomized controlled trial (n = 52), app users had a significantly higher knowledge of contraceptive effectiveness (P = .0001) and increased interest in the implant (7.1-32.1%, P = .02) after the intervention. Users were highly satisfied with the app. Staff reported no problems using the app in the clinic. Use of a theory-based counseling app offers a novel method to optimize wait time while minimizing clinic flow disruption. Preliminary data demonstrate that app use was associated with improvements in patients' contraceptive knowledge and interest in the implant. Copyright © 2014 Elsevier Inc. All rights reserved.

Blocking for Sequential Political Experiments

PubMed Central

Moore, Sally A.

2013-01-01

In typical political experiments, researchers randomize a set of households, precincts, or individuals to treatments all at once, and characteristics of all units are known at the time of randomization. However, in many other experiments, subjects “trickle in” to be randomized to treatment conditions, usually via complete randomization. To take advantage of the rich background data that researchers often have (but underutilize) in these experiments, we develop methods that use continuous covariates to assign treatments sequentially. We build on biased coin and minimization procedures for discrete covariates and demonstrate that our methods outperform complete randomization, producing better covariate balance in simulated data. We then describe how we selected and deployed a sequential blocking method in a clinical trial and demonstrate the advantages of our having done so. Further, we show how that method would have performed in two larger sequential political trials. Finally, we compare causal effect estimates from differences in means, augmented inverse propensity weighted estimators, and randomization test inversion. PMID:24143061

Coordination and Management of Multisite Complementary and Alternative Medicine (CAM) Therapies: Experience from a Multisite Reflexology Intervention Trial

PubMed Central

Rahbar, Mohammad H.; Wyatt, Gwen; Sikorskii, Alla; Victorson, David; Ardjomand-Hessabi, Manouchehr

2011-01-01

Background Multisite randomized clinical trials allow for increased research collaboration among investigators and expedite data collection efforts. As a result, government funding agencies typically look favorably upon this approach. As the field of complementary and alternative medicine (CAM) continues to evolve, so do increased calls for the use of more rigorous study design and trial methodologies, which can present challenges for investigators. Purpose To describe the processes involved in the coordination and management of a multisite randomized clinical trial of a CAM intervention. Methods Key aspects related to the coordination and management of a multisite CAM randomized clinical trial are presented, including organizational and site selection considerations, recruitment concerns and issues related to data collection and randomization to treatment groups. Management and monitoring of data, as well as quality assurance procedures are described. Finally, a real world perspective is shared from a recently conducted multisite randomized clinical trial of reflexology for women diagnosed with advanced breast cancer. Results The use of multiple sites in the conduct of CAM-based randomized clinical trials can provide an efficient, collaborative and robust approach to study coordination and data collection that maximizes efficiency and ensures the quality of results. Conclusions Multisite randomized clinical trial designs can offer the field of CAM research a more standardized and efficient approach to examine the effectiveness of novel therapies and treatments. Special attention must be given to intervention fidelity, consistent data collection and ensuring data quality. Assessment and reporting of quantitative indicators of data quality should be required. PMID:21664296

Evaluation of active and passive recruitment methods used in randomized controlled trials targeting pediatric obesity

PubMed Central

RAYNOR, HOLLIE A.; OSTERHOLT, KATHRIN M.; HART, CHANTELLE N.; JELALIAN, ELISSA; VIVIER, PATRICK; WING, RENA R.

2016-01-01

Objective Evaluate enrollment numbers, randomization rates, costs, and cost-effectiveness of active versus passive recruitment methods for parent-child dyads into two pediatric obesity intervention trials. Methods Recruitment methods were categorized into active (pediatrician referral and targeted mailings, with participants identified by researcher/health care provider) versus passive methods (newspaper, bus, internet, television, and earning statements; fairs/community centers/schools; and word of mouth; with participants self-identified). Numbers of enrolled and randomized families and costs/recruitment method were monitored throughout the 22-month recruitment period. Costs (in USD) per recruitment method included staff time, mileage, and targeted costs of each method. Results A total of 940 families were referred or made contact, with 164 families randomized (child: 7.2±1.6 years, 2.27±0.61 standardized body mass index [zBMI], 86.6% obese, 61.7% female, 83.5% white; parent: 38.0±5.8 years, 32.9±8.4 BMI, 55.2% obese, 92.7% female, 89.6% white). Pediatrician referral, followed by targeted mailings, produced the largest number of enrolled and randomized families (both methods combined producing 87.2% of randomized families). Passive recruitment methods yielded better retention from enrollment to randomization (p <0.05), but produced few families (21 in total). Approximately $91 000 was spent on recruitment, with cost per randomized family at $554.77. Pediatrician referral was the most cost-effective method, $145.95/randomized family, but yielded only 91 randomized families over 22-months of continuous recruitment. Conclusion Pediatrician referral and targeted mailings, which are active recruitment methods, were the most successful strategies. However, recruitment demanded significant resources. Successful recruitment for pediatric trials should use several strategies. Clinical Trials Registration: NCT00259324, NCT00200265 PMID:19922036

Randomized clinical trials in dentistry: Risks of bias, risks of random errors, reporting quality, and methodologic quality over the years 1955–2013

PubMed Central

Armijo-Olivo, Susan; Cummings, Greta G.; Amin, Maryam; Flores-Mir, Carlos

2017-01-01

Objectives To examine the risks of bias, risks of random errors, reporting quality, and methodological quality of randomized clinical trials of oral health interventions and the development of these aspects over time. Methods We included 540 randomized clinical trials from 64 selected systematic reviews. We extracted, in duplicate, details from each of the selected randomized clinical trials with respect to publication and trial characteristics, reporting and methodologic characteristics, and Cochrane risk of bias domains. We analyzed data using logistic regression and Chi-square statistics. Results Sequence generation was assessed to be inadequate (at unclear or high risk of bias) in 68% (n = 367) of the trials, while allocation concealment was inadequate in the majority of trials (n = 464; 85.9%). Blinding of participants and blinding of the outcome assessment were judged to be inadequate in 28.5% (n = 154) and 40.5% (n = 219) of the trials, respectively. A sample size calculation before the initiation of the study was not performed/reported in 79.1% (n = 427) of the trials, while the sample size was assessed as adequate in only 17.6% (n = 95) of the trials. Two thirds of the trials were not described as double blinded (n = 358; 66.3%), while the method of blinding was appropriate in 53% (n = 286) of the trials. We identified a significant decrease over time (1955–2013) in the proportion of trials assessed as having inadequately addressed methodological quality items (P < 0.05) in 30 out of the 40 quality criteria, or as being inadequate (at high or unclear risk of bias) in five domains of the Cochrane risk of bias tool: sequence generation, allocation concealment, incomplete outcome data, other sources of bias, and overall risk of bias. Conclusions The risks of bias, risks of random errors, reporting quality, and methodological quality of randomized clinical trials of oral health interventions have improved over time; however, further efforts that contribute to the development of more stringent methodology and detailed reporting of trials are still needed. PMID:29272315

A randomized controlled pilot trial comparing the impact of access to clinical endocrinology video demonstrations with access to usual revision resources on medical student performance of clinical endocrinology skills.

PubMed

Hibbert, Emily J; Lambert, Tim; Carter, John N; Learoyd, Diana L; Twigg, Stephen; Clarke, Stephen

2013-10-03

Demonstrating competence in clinical skills is key to course completion for medical students. Methods of providing clinical instruction that foster immediate learning and potentially serve as longer-term repositories for on-demand revision, such as online videos demonstrating competent performance of clinical skills, are increasingly being used. However, their impact on learning has been little studied. The aim of this study was to determine the value of adjunctive on-demand video-based training for clinical skills acquisition by medical students in endocrinology. Following an endocrinology clinical tutorial program, 2nd year medical students in the pre-assessment revision period were recruited and randomized to either a set of bespoke on-line clinical skills training videos (TV), or to revision as usual (RAU). The skills demonstrated on video were history taking in diabetes mellitus (DMH), examination for diabetes lower limb complications (LLE), and examination for signs of thyroid disease (TE). Students were assessed on these clinical skills in an observed structured clinical examination two weeks after randomization. Assessors were blinded to student randomization status. For both diabetes related clinical skills assessment tasks, students in the TV group performed significantly better than those in the RAU group. There were no between group differences in thyroid examination performance. For the LLE, 91.7% (n = 11/12) of students randomized to the video were rated globally as competent at the skill compared with 40% (n = 4/10) of students not randomized to the video (p = 0.024). For the DMH, 83.3% (n = 10/12) of students randomized to the video were rated globally as competent at the skill compared with 20% (n = 2/10) of students not randomized to the video (p = 0.007). Exposure to high quality videos demonstrating clinical skills can significantly improve medical student skill performance in an observed structured clinical examination of these skills, when used as an adjunct to clinical skills face-to-face tutorials and deliberate practice of skills in a blended learning format. Video demonstrations can provide an enduring, on-demand, portable resource for revision, which can even be used at the bedside by learners. Such resources are cost-effectively scalable for large numbers of learners.

Randomized trials published in some Chinese journals: how many are randomized?

PubMed Central

Wu, Taixiang; Li, Youping; Bian, Zhaoxiang; Liu, Guanjian; Moher, David

2009-01-01

Background The approximately 1100 medical journals now active in China are publishing a rapidly increasing number of research reports, including many studies identified by their authors as randomized controlled trials. It has been noticed that these reports mostly present positive results, and their quality and authenticity have consequently been called into question. We investigated the adequacy of randomization of clinical trials published in recent years in China to determine how many of them met acceptable standards for allocating participants to treatment groups. Methods The China National Knowledge Infrastructure electronic database was searched for reports of randomized controlled trials on 20 common diseases published from January 1994 to June 2005. From this sample, a subset of trials that appeared to have used randomization methods was selected. Twenty-one investigators trained in the relevant knowledge, communication skills and quality control issues interviewed the original authors of these trials about the participant randomization methods and related quality-control features of their trials. Results From an initial sample of 37,313 articles identified in the China National Knowledge Infrastructure database, we found 3137 apparent randomized controlled trials. Of these, 1452 were studies of conventional medicine (published in 411 journals) and 1685 were studies of traditional Chinese medicine (published in 352 journals). Interviews with the authors of 2235 of these reports revealed that only 207 studies adhered to accepted methodology for randomization and could on those grounds be deemed authentic randomized controlled trials (6.8%, 95% confidence interval 5.9–7.7). There was no statistically significant difference in the rate of authenticity between randomized controlled trials of traditional interventions and those of conventional interventions. Randomized controlled trials conducted at hospitals affiliated to medical universities were more likely to be authentic than trials conducted at level 3 and level 2 hospitals (relative risk 1.58, 95% confidence interval 1.18–2.13, and relative risk 14.42, 95% confidence interval 9.40–22.10, respectively). The likelihood of authenticity was higher in level 3 hospitals than in level 2 hospitals (relative risk 9.32, 95% confidence interval 5.83–14.89). All randomized controlled trials of pre-market drug clinical trial were authentic by our criteria. Of the trials conducted at university-affiliated hospitals, 56.3% were authentic (95% confidence interval 32.0–81.0). Conclusion Most reports of randomized controlled trials published in some Chinese journals lacked an adequate description of randomization. Similarly, most so called 'randomized controlled trials' were not real randomized controlled trials owing toa lack of adequate understanding on the part of the authors of rigorous clinical trial design. All randomized controlled trials of pre-market drug clinical trial included in this research were authentic. Randomized controlled trials conducted by authors in high level hospitals, especially in hospitals affiliated to medical universities had a higher rate of authenticity. That so many non-randomized controlled trials were published as randomized controlled trials reflected the fact that peer review needs to be improved and a good practice guide for peer review including how to identify the authenticity of the study urgently needs to be developed. PMID:19573242

Design and challenges of a randomized controlled trial for reducing risk factors of metabolic syndrome in Mexican women through water intake

PubMed Central

Hernández-Cordero, Sonia; González-Castell, Dinorah; Rodríguez-Ramírez, Sonia; Villanueva-Borbolla, María Ángeles; Unar, Mishel; Barquera, Simón; de Cossío, Teresita González; Rivera-Dommarco, Juan; Popkin, Barry M

2014-01-01

Objective To describe the design, methods, and challenges encountered during a randomized clinical trial aimed to promote water intake for reducing risks of metabolic syndrome in Mexican women. Materials and methods In a randomized clinical trial in Cuernavaca, Mexico, overweight and obese (body mass index [BMI] ≥ 25 < 39) women, 18 – < 45 years old with an intake of sugar-sweetened beverages ≥ 250 kilocalories per day (kcal/day) were randomly allocated to the water and education provision group (n = 120) or the education provision only group (n = 120). Results We screened 1 756 women. The main difficulties encountered were identifying participants with the recruitment criteria, delivering water to participants, and the time demanded from the study participants. Conclusions The trial’s main challenges were difficulties surrounding recruitment, delivery of the intervention, and the time demanded from the study participants. Modifications were effectively implemented without jeopardizing the original protocol. PMID:24715012

Clinical Trials in Dentistry: A Cross-sectional Analysis of World Health Organization-International Clinical Trial Registry Platform.

PubMed

Sivaramakrishnan, Gowri; Sridharan, Kannan

2016-06-01

Clinical trials are the back bone for evidence-based practice (EBP) and recently EBP has been considered the best source of treatment strategies available. Clinical trial registries serve as databases of clinical trials. As regards to dentistry in specific data on the number of clinical trials and their quality is lacking. Hence, the present study was envisaged. Clinical trials registered in WHO-ICTRP (http://apps.who.int/trialsearch/AdvSearch.aspx) in dental specialties were considered. The details assessed from the collected trials include: Type of sponsors; Health condition; Recruitment status; Study design; randomization, method of randomization and allocation concealment; Single or multi-centric; Retrospective or prospective registration; and Publication status in case of completed studies. A total of 197 trials were identified. Maximum trials were from United States (n = 30) and United Kingdom (n = 38). Seventy six trials were registered in Clinical Trials.gov, 54 from International Standards of Reporting Clinical Trials, 13 each from Australia and New Zealand Trial Register and Iranian Registry of Clinical Trials, 10 from German Clinical Trial Registry, eight each from Brazilian Clinical Trial Registry and Nederland's Trial Register, seven from Japan Clinical Trial Registry, six from Clinical Trial Registry of India and two from Hong Kong Clinical Trial Registry. A total of 78.7% studies were investigator-initiated and 64% were completed while 3% were terminated. Nearly four-fifths of the registered trials (81.7%) were interventional studies of which randomized were the large majority (94.4%) with 63.2% being open label, 20.4% using single blinding technique and 16.4% were doubled blinded. The number, methodology and the characteristics of clinical trials in dentistry have been noted to be poor especially in terms of being conducted multi-centrically, employing blinding and the method for randomization and allocation concealment. More emphasis has to be laid down on the quality of trials being conducted in order to provide justice in the name of EBP. Copyright © 2016 Elsevier Inc. All rights reserved.

Effectiveness of patient feedback as an educational intervention to improve medical student consultation (PTA Feedback Study): study protocol for a randomized controlled trial.

PubMed

Lai, Michelle Mei Yee; Roberts, Noel; Martin, Jenepher

2014-09-17

Oral feedback from clinical educators is the traditional teaching method for improving clinical consultation skills in medical students. New approaches are needed to enhance this teaching model. Multisource feedback is a commonly used assessment method for learning among practising clinicians, but this assessment has not been explored rigorously in medical student education. This study seeks to evaluate if additional feedback on patient satisfaction improves medical student performance. The Patient Teaching Associate (PTA) Feedback Study is a single site randomized controlled, double-blinded trial with two parallel groups.An after-hours general practitioner clinic in Victoria, Australia, is adapted as a teaching clinic during the day. Medical students from two universities in their first clinical year participate in six simulated clinical consultations with ambulatory patient volunteers living with chronic illness. Eligible students will be randomized in equal proportions to receive patient satisfaction score feedback with the usual multisource feedback and the usual multisource feedback alone as control. Block randomization will be performed. We will assess patient satisfaction and consultation performance outcomes at baseline and after one semester and will compare any change in mean scores at the last session from that at baseline. We will model data using regression analysis to determine any differences between intervention and control groups. Full ethical approval has been obtained for the study. This trial will comply with CONSORT guidelines and we will disseminate data at conferences and in peer-reviewed journals. This is the first proposed trial to determine whether consumer feedback enhances the use of multisource feedback in medical student education, and to assess the value of multisource feedback in teaching and learning about the management of ambulatory patients living with chronic conditions. Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12613001055796.

Effective Recruitment of Schools for Randomized Clinical Trials: Role of School Nurses.

PubMed

Petosa, R L; Smith, L

2017-01-01

In school settings, nurses lead efforts to improve the student health and well-being to support academic success. Nurses are guided by evidenced-based practice and data to inform care decisions. The randomized controlled trial (RCT) is considered the gold standard of scientific rigor for clinical trials. RCTs are critical to the development of evidence-based health promotion programs in schools. The purpose of this article is to present practical solutions to implementing principles of randomization to RCT trials conducted in school settings. Randomization is a powerful sampling method used to build internal and external validity. The school's daily organization and educational mission provide several barriers to randomization. Based on the authors' experience in conducting school-based RCTs, they offer a host of practical solutions to working with schools to successfully implement randomization procedures. Nurses play a critical role in implementing RCTs in schools to promote rigorous science in support of evidence-based practice.

Comparison of Time-to-First Event and Recurrent Event Methods in Randomized Clinical Trials.

PubMed

Claggett, Brian; Pocock, Stuart; Wei, L J; Pfeffer, Marc A; McMurray, John J V; Solomon, Scott D

2018-03-27

Background -Most Phase-3 trials feature time-to-first event endpoints for their primary and/or secondary analyses. In chronic diseases where a clinical event can occur more than once, recurrent-event methods have been proposed to more fully capture disease burden and have been assumed to improve statistical precision and power compared to conventional "time-to-first" methods. Methods -To better characterize factors that influence statistical properties of recurrent-events and time-to-first methods in the evaluation of randomized therapy, we repeatedly simulated trials with 1:1 randomization of 4000 patients to active vs control therapy, with true patient-level risk reduction of 20% (i.e. RR=0.80). For patients who discontinued active therapy after a first event, we assumed their risk reverted subsequently to their original placebo-level risk. Through simulation, we varied a) the degree of between-patient heterogeneity of risk and b) the extent of treatment discontinuation. Findings were compared with those from actual randomized clinical trials. Results -As the degree of between-patient heterogeneity of risk was increased, both time-to-first and recurrent-events methods lost statistical power to detect a true risk reduction and confidence intervals widened. The recurrent-events analyses continued to estimate the true RR=0.80 as heterogeneity increased, while the Cox model produced estimates that were attenuated. The power of recurrent-events methods declined as the rate of study drug discontinuation post-event increased. Recurrent-events methods provided greater power than time-to-first methods in scenarios where drug discontinuation was ≤30% following a first event, lesser power with drug discontinuation rates of ≥60%, and comparable power otherwise. We confirmed in several actual trials in chronic heart failure that treatment effect estimates were attenuated when estimated via the Cox model and that increased statistical power from recurrent-events methods was most pronounced in trials with lower treatment discontinuation rates. Conclusions -We find that the statistical power of both recurrent-events and time-to-first methods are reduced by increasing heterogeneity of patient risk, a parameter not included in conventional power and sample size formulas. Data from real clinical trials are consistent with simulation studies, confirming that the greatest statistical gains from use of recurrent-events methods occur in the presence of high patient heterogeneity and low rates of study drug discontinuation.

Preventing Cognitive Decline in Older African Americans with Mild Cognitive Impairment: Design and Methods of a Randomized Clinical Trial

PubMed Central

Rovner, Barry W.; Casten, Robin J.; Hegel, Mark T.; Leiby, Benjamin E.

2012-01-01

Mild Cognitive Impairment (MCI) affects 25% of older African Americans and predicts progression to Alzheimer's disease. An extensive epidemiologic literature suggests that cognitive, physical, and/or social activities may prevent cognitive decline. We describe the methods of a randomized clinical trial to test the efficacy of Behavior Activation to prevent cognitive decline in older African Americans with the amnestic multiple domain subtype of MCI. Community Health Workers deliver 6 initial in-home treatment sessions over 2-3 months and then 6 subsequent in-home booster sessions using language, materials, and concepts that are culturally relevant to older African Americans during this 24 month clinical trial. We are randomizing 200 subjects who are recruited from churches, senior centers, and medical clinics to Behavior Activation or Supportive Therapy, which controls for attention. The primary outcome is episodic memory as measured by the Hopkins Verbal Learning Test-Revised at baseline and at months 3, 12, 18, and 24. The secondary outcomes are general and domain-specific neuropsychological function, activities of daily living, depression, and quality-of-life. The negative results of recent clinical trials of drug treatments for MCI and Alzheimer's disease suggest that behavioral interventions may provide an alternative treatment approach to preserve cognition in an aging society. PMID:22406101

Some practical problems in implementing randomization.

PubMed

Downs, Matt; Tucker, Kathryn; Christ-Schmidt, Heidi; Wittes, Janet

2010-06-01

While often theoretically simple, implementing randomization to treatment in a masked, but confirmable, fashion can prove difficult in practice. At least three categories of problems occur in randomization: (1) bad judgment in the choice of method, (2) design and programming errors in implementing the method, and (3) human error during the conduct of the trial. This article focuses on these latter two types of errors, dealing operationally with what can go wrong after trial designers have selected the allocation method. We offer several case studies and corresponding recommendations for lessening the frequency of problems in allocating treatment or for mitigating the consequences of errors. Recommendations include: (1) reviewing the randomization schedule before starting a trial, (2) being especially cautious of systems that use on-demand random number generators, (3) drafting unambiguous randomization specifications, (4) performing thorough testing before entering a randomization system into production, (5) maintaining a dataset that captures the values investigators used to randomize participants, thereby allowing the process of treatment allocation to be reproduced and verified, (6) resisting the urge to correct errors that occur in individual treatment assignments, (7) preventing inadvertent unmasking to treatment assignments in kit allocations, and (8) checking a sample of study drug kits to allow detection of errors in drug packaging and labeling. Although we performed a literature search of documented randomization errors, the examples that we provide and the resultant recommendations are based largely on our own experience in industry-sponsored clinical trials. We do not know how representative our experience is or how common errors of the type we have seen occur. Our experience underscores the importance of verifying the integrity of the treatment allocation process before and during a trial. Clinical Trials 2010; 7: 235-245. http://ctj.sagepub.com.

Recruitment and accrual of women in a placebo-controlled clinical pilot study on manual therapy.

PubMed

Cambron, Jerrilyn A; Hawk, Cheryl; Evans, Roni; Long, Cynthia R

2004-06-01

To investigate the accrual rates and recruitment processes among 3 Midwestern sites during a pilot study on manual therapy for chronic pelvic pain. Multisite pilot study for a randomized, placebo-controlled clinical trial. Three chiropractic institutions in or near major metropolitan cities in the Midwestern United States. Thirty-nine women aged 18 to 45 with chronic pelvic pain of at least 6 months duration, diagnosed by a board certified gynecologist. The method of recruitment was collected for each individual who responded to an advertisement and completed an interviewer-administered telephone screen. Participants who were willing and eligible after 3 baseline visits were entered into a randomized clinical trial. The number of responses and accrual rates were determined for the overall study, each of the 3 treatment sites, and each of the 5 recruitment efforts. In this study, 355 women were screened over the telephone and 39 were randomized, making the rate of randomization approximately 10%. The most effective recruitment methods leading to randomization were direct mail (38%) and radio advertisements (34%). However, success of the recruitment process differed by site. Based on the accrual of this multisite pilot study, a full-scale trial would not be feasible using this study's parameters. However, useful information was gained on recruitment effectiveness, eligibility criteria, and screening protocols among the 3 metropolitan sites.

Methodology Series Module 5: Sampling Strategies.

PubMed

Setia, Maninder Singh

2016-01-01

Once the research question and the research design have been finalised, it is important to select the appropriate sample for the study. The method by which the researcher selects the sample is the ' Sampling Method'. There are essentially two types of sampling methods: 1) probability sampling - based on chance events (such as random numbers, flipping a coin etc.); and 2) non-probability sampling - based on researcher's choice, population that accessible & available. Some of the non-probability sampling methods are: purposive sampling, convenience sampling, or quota sampling. Random sampling method (such as simple random sample or stratified random sample) is a form of probability sampling. It is important to understand the different sampling methods used in clinical studies and mention this method clearly in the manuscript. The researcher should not misrepresent the sampling method in the manuscript (such as using the term ' random sample' when the researcher has used convenience sample). The sampling method will depend on the research question. For instance, the researcher may want to understand an issue in greater detail for one particular population rather than worry about the ' generalizability' of these results. In such a scenario, the researcher may want to use ' purposive sampling' for the study.

Design and methods for a randomized clinical trial treating comorbid obesity and major depressive disorder

PubMed Central

Schneider, Kristin L; Bodenlos, Jamie S; Ma, Yunsheng; Olendzki, Barbara; Oleski, Jessica; Merriam, Philip; Crawford, Sybil; Ockene, Ira S; Pagoto, Sherry L

2008-01-01

Background Obesity is often comorbid with depression and individuals with this comorbidity fare worse in behavioral weight loss treatment. Treating depression directly prior to behavioral weight loss treatment might bolster weight loss outcomes in this population, but this has not yet been tested in a randomized clinical trial. Methods and design This randomized clinical trial will examine whether behavior therapy for depression administered prior to standard weight loss treatment produces greater weight loss than standard weight loss treatment alone. Obese women with major depressive disorder (N = 174) will be recruited from primary care clinics and the community and randomly assigned to one of the two treatment conditions. Treatment will last 2 years, and will include a 6-month intensive treatment phase followed by an 18-month maintenance phase. Follow-up assessment will occur at 6-months and 1- and 2 years following randomization. The primary outcome is weight loss. The study was designed to provide 90% power for detecting a weight change difference between conditions of 3.1 kg (standard deviation of 5.5 kg) at 1-year assuming a 25% rate of loss to follow-up. Secondary outcomes include depression, physical activity, dietary intake, psychosocial variables and cardiovascular risk factors. Potential mediators (e.g., adherence, depression, physical activity and caloric intake) of the intervention effect on weight change will also be examined. Discussion Treating depression before administering intensive health behavior interventions could potentially boost the impact on both mental and physical health outcomes. Trial registration NCT00572520 PMID:18793398

Improved Cardiovascular Prevention Using Best CME Practices: A Randomized Trial

ERIC Educational Resources Information Center

Laprise, Rejean; Thivierge, Robert; Gosselin, Gilbert; Bujas-Bobanovic, Maja; Vandal, Sylvie; Paquette, Daniel; Luneau, Micheline; Julien, Pierre; Goulet, Serge; Desaulniers, Jean; Maltais, Paule

2009-01-01

Introduction: It was hypothesized that after a continuing medical education (CME) event, practice enablers and reinforcers addressing main clinical barriers to preventive care would be more effective in improving general practitioners' (GPs) adherence to cardiovascular guidelines than a CME event only. Methods: A cluster-randomized trial was…

Efficiency of a Care Coordination Model: A Randomized Study with Stroke Patients

ERIC Educational Resources Information Center

Claiborne, Nancy

2006-01-01

Objectives: This study investigated the efficiency of a social work care coordination model for stroke patients. Care coordination addresses patient care and treatment resources across the health care system to reduce risk, improve clinical outcomes, and maximize efficiency. Method: A randomly assigned, pre-post experimental design measured…

Methodology Series Module 5: Sampling Strategies

PubMed Central

Setia, Maninder Singh

2016-01-01

Once the research question and the research design have been finalised, it is important to select the appropriate sample for the study. The method by which the researcher selects the sample is the ‘ Sampling Method’. There are essentially two types of sampling methods: 1) probability sampling – based on chance events (such as random numbers, flipping a coin etc.); and 2) non-probability sampling – based on researcher's choice, population that accessible & available. Some of the non-probability sampling methods are: purposive sampling, convenience sampling, or quota sampling. Random sampling method (such as simple random sample or stratified random sample) is a form of probability sampling. It is important to understand the different sampling methods used in clinical studies and mention this method clearly in the manuscript. The researcher should not misrepresent the sampling method in the manuscript (such as using the term ‘ random sample’ when the researcher has used convenience sample). The sampling method will depend on the research question. For instance, the researcher may want to understand an issue in greater detail for one particular population rather than worry about the ‘ generalizability’ of these results. In such a scenario, the researcher may want to use ‘ purposive sampling’ for the study. PMID:27688438

Randomization in cancer clinical trials: permutation test and development of a computer program.

PubMed Central

Ohashi, Y

1990-01-01

When analyzing cancer clinical trial data where the treatment allocation is done using dynamic balancing methods such as the minimization method for balancing the distribution of important prognostic factors in each arm, conservativeness occurs if such a randomization scheme is ignored and a simple unstratified analysis is carried out. In this paper, the above conservativeness is demonstrated by computer simulation, and the development of a computer program that carries out permutation tests of the log-rank statistics for clinical trial data where the allocation is done by the minimization method or a stratified permuted block design is introduced. We are planning to use this program in practice to supplement a usual stratified analysis and model-based methods such as the Cox regression. The most serious problem in cancer clinical trials in Japan is how to carry out the quality control or data management in trials that are initiated and conducted by researchers without support from pharmaceutical companies. In the final section of this paper, one international collaborative work for developing international guidelines on data management in clinical trials of bladder cancer is briefly introduced, and the differences between the system adopted in US/European statistical centers and the Japanese system is described. PMID:2269216

The impact of loss to follow-up on hypothesis tests of the treatment effect for several statistical methods in substance abuse clinical trials.

PubMed

Hedden, Sarra L; Woolson, Robert F; Carter, Rickey E; Palesch, Yuko; Upadhyaya, Himanshu P; Malcolm, Robert J

2009-07-01

"Loss to follow-up" can be substantial in substance abuse clinical trials. When extensive losses to follow-up occur, one must cautiously analyze and interpret the findings of a research study. Aims of this project were to introduce the types of missing data mechanisms and describe several methods for analyzing data with loss to follow-up. Furthermore, a simulation study compared Type I error and power of several methods when missing data amount and mechanism varies. Methods compared were the following: Last observation carried forward (LOCF), multiple imputation (MI), modified stratified summary statistics (SSS), and mixed effects models. Results demonstrated nominal Type I error for all methods; power was high for all methods except LOCF. Mixed effect model, modified SSS, and MI are generally recommended for use; however, many methods require that the data are missing at random or missing completely at random (i.e., "ignorable"). If the missing data are presumed to be nonignorable, a sensitivity analysis is recommended.

Randomized Multicenter Feasibility Trial of Myofascial Physical Therapy for Treatment of Urologic Chronic Pelvic Pain Syndrome

PubMed Central

FitzGerald, Mary P; Anderson, Rodney U; Potts, Jeannette; Payne, Christopher K; Peters, Kenneth M; Clemens, J Quentin; Kotarinos, Rhonda; Fraser, Laura; Cosby, Annamarie; Fortman, Carole; Neville, Cynthia; Badillo, Suzanne; Odabachian, Lisa; Sanfield, Anna; O’Dougherty, Betsy; Halle-Podell, Rick; Cen, Liyi; Chuai, Shannon; Landis, J Richard; Kusek, John W; Nyberg, Leroy M

2010-01-01

Objectives To determine the feasibility of conducting a randomized clinical trial designed to compare two methods of manual therapy (myofascial physical therapy (MPT) and global therapeutic massage (GTM)) among patients with urologic chronic pelvic pain syndromes. Materials and Methods Our goal was to recruit 48 subjects with chronic prostatitis/chronic pelvic pain syndrome or interstitial cystitis/painful bladder syndrome at six clinical centers. Eligible patients were randomized to either MPT or GTM and were scheduled to receive up to 10 weekly treatments, each 1 hour in duration. Criteria to assess feasibility included adherence of therapists to prescribed therapeutic protocol as determined by records of treatment, adverse events which occurred during study treatment, and rate of response to therapy as assessed by the Patient Global Response Assessment (GRA). Primary outcome analysis compared response rates between treatment arms using Mantel-Haenszel methods. Results Twenty-three (49%) men and 24 (51%) women were randomized over a six month period. Twenty-four (51%) patients were randomized to GTM, 23 (49%) to MPT; 44 (94%) patients completed the study. Therapist adherence to the treatment protocols was excellent. The GRA response rate of 57% in the MPT group was significantly higher than the rate of 21% in the GTM treatment group (p=0.03). Conclusions The goals to judge feasibility of conducting a full-scale trial of physical therapy methods were met. The preliminary findings of a beneficial effect of MPT warrants further study. PMID:19535099

Millon Clinical Multiaxial Inventory-III Subtypes of Opioid Dependence: Validity and Matching to Behavioral Therapies

ERIC Educational Resources Information Center

Ball, Samuel A.; Nich, Charla; Rounsaville, Bruce J.; Eagan, Dorothy; Carroll, Kathleen M.

2004-01-01

The concurrent and predictive validity of 2 different methods of Millon Clinical Multiaxial Inventory-III subtyping (protocol sorting, cluster analysis) was evaluated in 125 recently detoxified opioid-dependent outpatients in a 12-week randomized clinical trial. Participants received naltrexone and relapse prevention group counseling and were…

[Computer-assisted education in problem-solving in neurology; a randomized educational study].

PubMed

Weverling, G J; Stam, J; ten Cate, T J; van Crevel, H

1996-02-24

To determine the effect of computer-based medical teaching (CBMT) as a supplementary method to teach clinical problem-solving during the clerkship in neurology. Randomized controlled blinded study. Academic Medical Centre, Amsterdam, the Netherlands. 103 Students were assigned at random to a group with access to CBMT and a control group. CBMT consisted of 20 computer-simulated patients with neurological diseases, and was permanently available during five weeks to students in the CBMT group. The ability to recognize and solve neurological problems was assessed with two free-response tests, scored by two blinded observers. The CBMT students scored significantly better on the test related to the CBMT cases (mean score 7.5 on a zero to 10 point scale; control group 6.2; p < 0.001). There was no significant difference on the control test not related to the problems practised with CBMT. CBMT can be an effective method for teaching clinical problem-solving, when used as a supplementary teaching facility during a clinical clerkship. The increased ability to solve problems learned by CBMT had no demonstrable effect on the performance with other neurological problems.

Analysis of nonintervention studies: technical supplement.

PubMed

Aickin, Mikel

2012-01-01

Methods for analyzing data in nonintervention clinical studies are substantially different from those that are appropriate for randomized clinical trials. Although the latter methods are well known, the former are not. A systematic approach for dealing with statistical confounding in nonintervention research has been developed over the past 30 to 40 years, and the essence of this theory constitutes the contents of this article. An accompanying, less technical article explains the implications of these results for clinical research.

Clinical trial design for orthodontists.

PubMed

Pandis, Nikolaos; Cobourne, Martyn T

2013-06-01

High-quality research should form the basis of all clinical practice. Randomized controlled trials currently provide the gold standard for investigating the effectiveness of treatment interventions and these are increasingly being used in orthodontics. Here we discuss the reasons why this form of investigation provides the most useful evidence for assessing treatment outcome. The methods available to achieve true randomization, a fundamental component in the design of these trials, are also discussed. In addition, we focus on how to minimize bias in clinical research, not only during the design and management of a trial, but also when disseminating results. We focus on the importance of using control groups correctly and describe methods that are available to adequately power a trial. Finally, we emphasise the importance of accurate and transparent reporting, which facilitates correct communication and assessment of the evidence.

A Randomized Phase II Dose-Response Exercise Trial among Colon Cancer Survivors: Purpose, Study Design, Methods, and Recruitment Results

PubMed Central

Brown, Justin C.; Troxel, Andrea B.; Ky, Bonnie; Damjanov, Nevena; Zemel, Babette S.; Rickels, Michael R.; Rhim, Andrew D.; Rustgi, Anil K.; Courneya, Kerry S.; Schmitz, Kathryn H.

2016-01-01

Background Observational studies indicate that higher volumes of physical activity are associated with improved disease outcomes among colon cancer survivors. The aim of this report is to describe the purpose, study design, methods, and recruitment results of the COURAGE trial, a National Cancer Institute (NCI) sponsored, phase II, randomized, dose-response exercise trial among colon cancer survivors. Methods/Results The primary objective of the COURAGE trial is to quantify the feasibility, safety, and physiologic effects of low-dose (150 min·wk−1) and high-dose (300 min·wk−1) moderate-intensity aerobic exercise compared to usual-care control group over six months. The exercise groups are provided with in-home treadmills and heart rate monitors. Between January and July 2015, 1,433 letters were mailed using a population-based state cancer registry; 126 colon cancer survivors inquired about participation, and 39 were randomized onto the study protocol. Age was associated with inquiry about study participation (P<0.001) and randomization onto the study protocol (P<0.001). No other demographic, clinical, or geographic characteristics were associated with study inquiry or randomization. The final trial participant was randomized in August 2015. Six month endpoint data collection was completed in February 2016. Discussion The recruitment of colon cancer survivors into an exercise trial is feasible. The findings from this trial will inform key design aspects for future phase 2 and phase 3 randomized controlled trials to examine the efficacy of exercise to improve clinical outcomes among colon cancer survivors. PMID:26970181

Bayesian randomized clinical trials: From fixed to adaptive design.

PubMed

Yin, Guosheng; Lam, Chi Kin; Shi, Haolun

2017-08-01

Randomized controlled studies are the gold standard for phase III clinical trials. Using α-spending functions to control the overall type I error rate, group sequential methods are well established and have been dominating phase III studies. Bayesian randomized design, on the other hand, can be viewed as a complement instead of competitive approach to the frequentist methods. For the fixed Bayesian design, the hypothesis testing can be cast in the posterior probability or Bayes factor framework, which has a direct link to the frequentist type I error rate. Bayesian group sequential design relies upon Bayesian decision-theoretic approaches based on backward induction, which is often computationally intensive. Compared with the frequentist approaches, Bayesian methods have several advantages. The posterior predictive probability serves as a useful and convenient tool for trial monitoring, and can be updated at any time as the data accrue during the trial. The Bayesian decision-theoretic framework possesses a direct link to the decision making in the practical setting, and can be modeled more realistically to reflect the actual cost-benefit analysis during the drug development process. Other merits include the possibility of hierarchical modeling and the use of informative priors, which would lead to a more comprehensive utilization of information from both historical and longitudinal data. From fixed to adaptive design, we focus on Bayesian randomized controlled clinical trials and make extensive comparisons with frequentist counterparts through numerical studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Design and methods for a pilot randomized clinical trial involving exercise and behavioral activation to treat comorbid type 2 diabetes and major depressive disorder

PubMed Central

Schneider, Kristin L.; Pagoto, Sherry L.; Handschin, Barbara; Panza, Emily; Bakke, Susan; Liu, Qin; Blendea, Mihaela; Ockene, Ira S.; Ma, Yunsheng

2011-01-01

Background The comorbidity of type 2 diabetes mellitus (T2DM) and depression is associated with poor glycemic control. Exercise has been shown to improve mood and glycemic control, but individuals with comorbid T2DM and depression are disproportionately sedentary compared to the general population and report more difficulty with exercise. Behavioral activation, an evidence-based depression psychotherapy, was designed to help people with depression make gradual behavior changes, and may be helpful to build exercise adherence in sedentary populations. This pilot randomized clinical trial will test the feasibility of a group exercise program enhanced with behavioral activation strategies among women with comorbid T2DM and depression. Methods/Design Sedentary women with inadequately controlled T2DM and depression (N=60) will be randomly assigned to one of two conditions: exercise or usual care. Participants randomized to the exercise condition will attend 38 behavioral activation-enhanced group exercise classes over 24 weeks in addition to usual care. Participants randomized to the usual care condition will receive depression treatment referrals and print information on diabetes management via diet and physical activity. Assessments will occur at baseline and 3-, 6-, and 9-months following randomization. The goals of this pilot study are to demonstrate feasibility and intervention acceptability, estimate the resources and costs required to deliver the intervention and to estimate the standard deviation of continuous outcomes (e.g., depressive symptoms and glycosylated hemoglobin) in preparation for a fully-powered randomized clinical trial. Discussion A novel intervention that combines exercise and behavioral activation strategies could potentially improve glycemic control and mood in women with comorbid type 2 diabetes and depression. Trial registration NCT01024790 PMID:21765864

A Bayesian comparative effectiveness trial in action: developing a platform for multisite study adaptive randomization.

PubMed

Brown, Alexandra R; Gajewski, Byron J; Aaronson, Lauren S; Mudaranthakam, Dinesh Pal; Hunt, Suzanne L; Berry, Scott M; Quintana, Melanie; Pasnoor, Mamatha; Dimachkie, Mazen M; Jawdat, Omar; Herbelin, Laura; Barohn, Richard J

2016-08-31

In the last few decades, the number of trials using Bayesian methods has grown rapidly. Publications prior to 1990 included only three clinical trials that used Bayesian methods, but that number quickly jumped to 19 in the 1990s and to 99 from 2000 to 2012. While this literature provides many examples of Bayesian Adaptive Designs (BAD), none of the papers that are available walks the reader through the detailed process of conducting a BAD. This paper fills that gap by describing the BAD process used for one comparative effectiveness trial (Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations) that can be generalized for use by others. A BAD was chosen with efficiency in mind. Response-adaptive randomization allows the potential for substantially smaller sample sizes, and can provide faster conclusions about which treatment or treatments are most effective. An Internet-based electronic data capture tool, which features a randomization module, facilitated data capture across study sites and an in-house computation software program was developed to implement the response-adaptive randomization. A process for adapting randomization with minimal interruption to study sites was developed. A new randomization table can be generated quickly and can be seamlessly integrated in the data capture tool with minimal interruption to study sites. This manuscript is the first to detail the technical process used to evaluate a multisite comparative effectiveness trial using adaptive randomization. An important opportunity for the application of Bayesian trials is in comparative effectiveness trials. The specific case study presented in this paper can be used as a model for conducting future clinical trials using a combination of statistical software and a web-based application. ClinicalTrials.gov Identifier: NCT02260388 , registered on 6 October 2014.

Treatment selection in a randomized clinical trial via covariate-specific treatment effect curves.

PubMed

Ma, Yunbei; Zhou, Xiao-Hua

2017-02-01

For time-to-event data in a randomized clinical trial, we proposed two new methods for selecting an optimal treatment for a patient based on the covariate-specific treatment effect curve, which is used to represent the clinical utility of a predictive biomarker. To select an optimal treatment for a patient with a specific biomarker value, we proposed pointwise confidence intervals for each covariate-specific treatment effect curve and the difference between covariate-specific treatment effect curves of two treatments. Furthermore, to select an optimal treatment for a future biomarker-defined subpopulation of patients, we proposed confidence bands for each covariate-specific treatment effect curve and the difference between each pair of covariate-specific treatment effect curve over a fixed interval of biomarker values. We constructed the confidence bands based on a resampling technique. We also conducted simulation studies to evaluate finite-sample properties of the proposed estimation methods. Finally, we illustrated the application of the proposed method in a real-world data set.

Preventing Caries in Preschoolers: Successful Initiation of an Innovative Community-Based Clinical Trial in Navajo Nation Head Start

PubMed Central

Quissell, David O.; Bryant, Lucinda L.; Braun, Patricia A.; Cudeii, Diana; Johs, Nikolas; Smith, Vongphone L.; George, Carmen; Henderson, William G.; Albino, Judith

2014-01-01

Navajo Nation children have the greatest prevalence of early childhood caries in the United States. This protocol describes an innovative combination of community-based participatory research and clinical trial methods to rigorously test a lay native Community Oral Health Specialists-delivered oral health intervention, with the goal of reducing the progression of disease and improving family knowledge and behaviors. Methods/Design This cluster-randomized trial designed by researchers at the Center for Native Oral Health Research at the University of Colorado in conjunction with members of the Navajo Nation community compares outcomes between the manualized 2-year oral health fluoride varnish-oral health promotion intervention and usual care in the community (child-caregiver dyads from 26 Head Start classrooms in each study arm; total of 1016 dyads). Outcome assessment includes annual dental screening and an annual caregiver survey of knowledge, attitudes and behaviors; collection of cost data will support cost-benefit analyses. Discussion The study protocol meets all standards required of randomized clinical trials. Aligned with principles of community-based participatory research, extended interaction between members of the Navajo community and researchers preceded study initiation, and collaboration between project staff and a wide variety of community members informed the study design and implementation. We believe the benefits of adding CBPR methods to those of randomized clinical studies outweigh the barriers and constraints, especially in studies of health disparities and in challenging settings. When done well, this innovative mix of methods will increase the likelihood of valid results that communities can use. PMID:24469238

Clinical Knowledge from Observational Studies: Everything You Wanted to Know but Were Afraid to Ask.

PubMed

Gershon, Andrea S; Jafarzadeh, S Reza; Wilson, Kevin C; Walkey, Allan J

2018-05-07

Well-done randomized trials provide accurate estimates of treatment effect by producing groups that are similar on all measures except for the intervention of interest. However, inferences of efficacy in tightly-controlled experimental settings may not translate into similar effectiveness in real-world settings. Observational studies generally enable inferences over a wider range of patient characteristics and evaluation of a broader range of outcomes over a longer period than randomized trials. However, clinicians are often reluctant to incorporate the findings of observational studies into clinical practice. Reason for uncertainty regarding observational studies include a lack of familiarity with observational research methods, occasional disagreements between results of observational studies and randomized trials, the perceived risk of spurious results from systematic bias, and prior teaching that randomized trials are the most reliable source of medical evidence. We propose that a better understanding of observational research will enhance clinicians' ability to distinguish reliable observational studies from those that are subjected to biases and, therefore, provide more confidence to apply observational research results into clinical practice when appropriate. Herein, we explain why observational studies may be perceived as less conclusive than randomized trials, address situations in which observational research and randomized trials produced different findings, and provide information on observational study design so that quality can be evaluated. We conclude that observational research is a valuable source of medical evidence and that clinical action is strongest when supported by both high quality observational studies and randomized trials.

EEG Neurofeedback for ADHD: Double-Blind Sham-Controlled Randomized Pilot Feasibility Trial

ERIC Educational Resources Information Center

Arnold, L. Eugene; Lofthouse, Nicholas; Hersch, Sarah; Pan, Xueliang; Hurt, Elizabeth; Bates, Bethany; Kassouf, Kathleen; Moone, Stacey; Grantier, Cara

2013-01-01

Objective: Preparing for a definitive randomized clinical trial (RCT) of neurofeedback (NF) for ADHD, this pilot trial explored feasibility of a double-blind, sham-controlled design and adherence/palatability/relative effect of two versus three treatments/week. Method: Unmedicated 6- to 12-year-olds with "Diagnostic and Statistical Manual of…

The feasibility of a randomized controlled trial of esophagectomy for esophageal cancer - the ROMIO (Randomized Oesophagectomy: Minimally Invasive or Open) study: protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background There is a need for evidence of the clinical effectiveness of minimally invasive surgery for the treatment of esophageal cancer, but randomized controlled trials in surgery are often difficult to conduct. The ROMIO (Randomized Open or Minimally Invasive Oesophagectomy) study will establish the feasibility of a main trial which will examine the clinical and cost-effectiveness of minimally invasive and open surgical procedures for the treatment of esophageal cancer. Methods/Design A pilot randomized controlled trial (RCT), in two centers (University Hospitals Bristol NHS Foundation Trust and Plymouth Hospitals NHS Trust) will examine numbers of incident and eligible patients who consent to participate in the ROMIO study. Interventions will include esophagectomy by: (1) open gastric mobilization and right thoracotomy, (2) laparoscopic gastric mobilization and right thoracotomy, and (3) totally minimally invasive surgery (in the Bristol center only). The primary outcomes of the feasibility study will be measures of recruitment, successful development of methods to monitor quality of surgery and fidelity to a surgical protocol, and development of a core outcome set to evaluate esophageal cancer surgery. The study will test patient-reported outcomes measures to assess recovery, methods to blind participants, assessments of surgical morbidity, and methods to capture cost and resource use. ROMIO will integrate methods to monitor and improve recruitment using audio recordings of consultations between recruiting surgeons, nurses, and patients to provide feedback for recruiting staff. Discussion The ROMIO study aims to establish efficient methods to undertake a main trial of minimally invasive surgery versus open surgery for esophageal cancer. Trial registration The pilot trial has Current Controlled Trials registration number ISRCTN59036820(25/02/2013) at http://www.controlled-trials.com; the ROMIO trial record at that site gives a link to the original version of the study protocol. PMID:24888266

Public Funding for Contraception, Provider Training, and Use of Highly Effective Contraceptives: A Cluster Randomized Trial

PubMed Central

Rocca, Corinne H.; Kohn, Julia E.; Goodman, Suzan; Stern, Lisa; Blum, Maya; Speidel, J. Joseph; Darney, Philip D.; Harper, Cynthia C.

2016-01-01

Objectives. We determined whether public funding for contraception was associated with long-acting reversible contraceptive (LARC) use when providers received training on these methods. Methods. We evaluated the impact of a clinic training intervention and public funding on LARC use in a cluster randomized trial at 40 randomly assigned clinics across the United States (2011–2013). Twenty intervention clinics received a 4-hour training. Women aged 18 to 25 were enrolled and followed for 1 year (n = 1500: 802 intervention, 698 control). We estimated the effects of the intervention and funding sources on LARC initiation with Cox proportional hazards models with shared frailty. Results. Women at intervention sites had higher LARC initiation than those at control (22 vs 18 per 100 person-years; adjusted hazard ratio [AHR] = 1.43; 95% confidence interval [CI] = 1.04, 1.98). Participants receiving care at clinics with Medicaid family planning expansion programs had almost twice the initiation rate as those at clinics without (25 vs 13 per 100 person-years; AHR = 2.26; 95% CI = 1.59, 3.19). LARC initiation also increased among participants with public (AHR = 1.56; 95% CI = 1.09, 2.22) but not private health insurance. Conclusions. Public funding and provider training substantially improve LARC access. PMID:26794168

Evaluation of the acceptability, feasibility and effectiveness of two methods of involving patients with disability in developing clinical guidelines: study protocol of a randomized pragmatic pilot trial.

PubMed

Lamontagne, Marie-Eve; Perreault, Kadija; Gagnon, Marie-Pierre

2014-04-10

Despite growing interest in the importance of, and challenges associated with the involvement of patient and population (IPP) in the process of developing and adapting clinical practice guidelines (CPGs), there is a lack of knowledge about the best method to use. This is especially problematic in the field of rehabilitation, where individuals with disabilities might face many barriers to their involvement in the guideline development and adaptation process. The goal of this pilot trial is to document the acceptability, feasibility and effectiveness of two methods of involving patients with a disability (traumatic brain injury) in CPG development. A single-blind, randomized, crossover pragmatic trial will be performed with 20 patients with traumatic brain injury (TBI). They will be randomized into two groups, and each will try two alternative methods of producing recommendations; a discussion group (control intervention) and a Wiki, a webpage that can be modified by those who have access to it (experimental intervention). The participants will rate the acceptability of the two methods, and feasibility will be assessed using indicators such as the number of participants who accessed and completed the two methods, and the number of support interventions required. Twenty experts, blinded to the method of producing the recommendations, will independently rate the recommendations produced by the participants for clarity, accuracy, appropriateness and usefulness. Our trial will allow for the use of optimal IPP methods in a larger project of adapting guidelines for the rehabilitation of individuals with TBI. Ultimately the results will inform the science of CPG development and contribute to the growing knowledge about IPP in rehabilitation settings. Clinical trial KT Canada 87776.

Improving Weight Maintenance Using Virtual Reality (Second Life)

ERIC Educational Resources Information Center

Sullivan, Debra K.; Goetz, Jeannine R.; Gibson, Cheryl A.; Washburn, Richard A.; Smith, Bryan K.; Lee, Jaehoon; Gerald, Stephanie; Fincham, Tennille; Donnelly, Joseph E.

2013-01-01

Objective: Compare weight loss and maintenance between a face-to-face (FTF) weight management clinic and a clinic delivered via virtual reality (VR). Methods: Participants were randomized to 3 months of weight loss with a weekly clinic delivered via FTF or VR and then 6 months' weight maintenance delivered with VR. Data were collected at baseline…

Eight-step method to build the clinical content of an evidence-based care pathway: the case for COPD exacerbation

PubMed Central

2012-01-01

Background Optimization of the clinical care process by integration of evidence-based knowledge is one of the active components in care pathways. When studying the impact of a care pathway by using a cluster-randomized design, standardization of the care pathway intervention is crucial. This methodology paper describes the development of the clinical content of an evidence-based care pathway for in-hospital management of chronic obstructive pulmonary disease (COPD) exacerbation in the context of a cluster-randomized controlled trial (cRCT) on care pathway effectiveness. Methods The clinical content of a care pathway for COPD exacerbation was developed based on recognized process design and guideline development methods. Subsequently, based on the COPD case study, a generalized eight-step method was designed to support the development of the clinical content of an evidence-based care pathway. Results A set of 38 evidence-based key interventions and a set of 24 process and 15 outcome indicators were developed in eight different steps. Nine Belgian multidisciplinary teams piloted both the set of key interventions and indicators. The key intervention set was judged by the teams as being valid and clinically applicable. In addition, the pilot study showed that the indicators were feasible for the involved clinicians and patients. Conclusions The set of 38 key interventions and the set of process and outcome indicators were found to be appropriate for the development and standardization of the clinical content of the COPD care pathway in the context of a cRCT on pathway effectiveness. The developed eight-step method may facilitate multidisciplinary teams caring for other patient populations in designing the clinical content of their future care pathways. PMID:23190552

A proposed method to investigate reliability throughout a questionnaire

PubMed Central

2011-01-01

Background Questionnaires are used extensively in medical and health care research and depend on validity and reliability. However, participants may differ in interest and awareness throughout long questionnaires, which can affect reliability of their answers. A method is proposed for "screening" of systematic change in random error, which could assess changed reliability of answers. Methods A simulation study was conducted to explore whether systematic change in reliability, expressed as changed random error, could be assessed using unsupervised classification of subjects by cluster analysis (CA) and estimation of intraclass correlation coefficient (ICC). The method was also applied on a clinical dataset from 753 cardiac patients using the Jalowiec Coping Scale. Results The simulation study showed a relationship between the systematic change in random error throughout a questionnaire and the slope between the estimated ICC for subjects classified by CA and successive items in a questionnaire. This slope was proposed as an awareness measure - to assessing if respondents provide only a random answer or one based on a substantial cognitive effort. Scales from different factor structures of Jalowiec Coping Scale had different effect on this awareness measure. Conclusions Even though assumptions in the simulation study might be limited compared to real datasets, the approach is promising for assessing systematic change in reliability throughout long questionnaires. Results from a clinical dataset indicated that the awareness measure differed between scales. PMID:21974842

Donepezil treatment and Alzheimer disease: can the results of randomized clinical trials be applied to Alzheimer disease patients in clinical practice?

PubMed

Tinklenberg, Jared R; Kraemer, Helena C; Yaffe, Kristine; Ross, Leslie; Sheikh, Javaid; Ashford, John W; Yesavage, Jerome A; Taylor, Joy L

2007-11-01

To determine if results from randomized clinical trials of donepezil in Alzheimer disease (AD) patients can be applied to AD patients in clinical practice by comparing the findings from a Nordic one-year randomized AD donepezil trial with data from a one-year prospective, observational study of AD patients. AD patients from a consortium of California sites were systematically followed for at least one year. Their treatment regimens, including prescription of donepezil, were determined by their individual physician according to his or her usual criteria. The 148 California patients treated with donepezil had a one-year decline of 1.3 (3.5 SD) points on the Mini-Mental State Exam compared to a decline of 3.3 (4.4 SD) in the 158 AD patients who received no anti-Alzheimer drugs. The Mini-Mental State Exam decline in Nordic sample was approximately 0.25 points for the 91 patients receiving donepezil and approximately 2.2 for the 98 placebo patients. The overall effect sizes were estimated at about 0.49 in both studies. The California data were further analyzed using propensity methods; after taking into account differences that could bias prescribing decisions, benefits associated with taking donepezil remained. A comparison of a randomized clinical trial of donepezil in AD patients and this observational study indicates that if appropriate methodological and statistical precautions are undertaken, then results from randomized clinical trials can be predictive with AD patients in clinical practice. This California study supports the modest effectiveness of donepezil in AD patients having clinical characteristics similar to those of the Nordic study.

Recognizing and managing a deteriorating patient: a randomized controlled trial investigating the effectiveness of clinical simulation in improving clinical performance in undergraduate nursing students.

PubMed

Stayt, Louise Caroline; Merriman, Clair; Ricketts, Barry; Morton, Sean; Simpson, Trevor

2015-11-01

To report the results of a randomized controlled trial which explored the effectiveness of clinical simulation in improving the clinical performance of recognizing and managing an adult deteriorating patient in hospital. There is evidence that final year undergraduate nurses may lack knowledge, clinical skills and situation awareness required to manage a deteriorating patient competently. The effectiveness of clinical simulation as a strategy to teach the skills required to recognize and manage the early signs of deterioration needs to be evaluated. This study was a two centre phase II single, randomized, controlled trial with single blinded assessments. Data were collected in July 2013. Ninety-eight first year nursing students were randomized either into a control group, where they received a traditional lecture, or an intervention group where they received simulation. Participants completed a pre- and postintervention objective structured clinical examination. General Perceived Self Efficacy and Self-Reported Competency scores were measured before and after the intervention. Student satisfaction with teaching was also surveyed. The intervention group performed significantly better in the post-objective structured clinical examination. There was no significant difference in the postintervention General Perceived Self Efficacy and Self-Reported Competency scores between the control and intervention group. The intervention group was significantly more satisfied with their teaching method. Simulation-based education may be an effective educational strategy to teach nurses the skills to effectively recognize and manage a deteriorating patient. © 2015 John Wiley & Sons Ltd.

Movement-Pattern Training to Improve Function in People With Chronic Hip Joint Pain: A Feasibility Randomized Clinical Trial.

PubMed

Harris-Hayes, Marcie; Czuppon, Sylvia; Van Dillen, Linda R; Steger-May, Karen; Sahrmann, Shirley; Schootman, Mario; Salsich, Gretchen B; Clohisy, John C; Mueller, Michael J

2016-06-01

Study Design Feasibility randomized clinical trial. Background Rehabilitation may be an appropriate treatment strategy for patients with chronic hip joint pain; however, the evidence related to the effectiveness of rehabilitation is limited. Objectives To assess feasibility of performing a randomized clinical trial to investigate the effectiveness of movement-pattern training (MPT) to improve function in people with chronic hip joint pain. Methods Thirty-five patients with chronic hip joint pain were randomized into a treatment (MPT) group or a control (wait-list) group. The MPT program included 6 one-hour supervised sessions and incorporated (1) task-specific training for basic functional tasks and symptom-provoking tasks, and (2) strengthening of hip musculature. The wait-list group received no treatment. Primary outcomes for feasibility were patient retention and adherence. Secondary outcomes to assess treatment effects were patient-reported function (Hip disability and Osteoarthritis Outcome Score), lower extremity kinematics, and hip muscle strength. Results Retention rates did not differ between the MPT (89%) and wait-list groups (94%, P = 1.0). Sixteen of the 18 patients (89%) in the MPT group attended at least 80% of the treatment sessions. For the home exercise program, 89% of patients reported performing their home program at least once per day. Secondary outcomes support the rationale for conduct of a superiority randomized clinical trial. Conclusion Based on retention and adherence rates, a larger randomized clinical trial appears feasible and warranted to assess treatment effects more precisely. Data from this feasibility study will inform our future clinical trial. Level of Evidence Therapy, level 2b-. J Orthop Sports Phys Ther 2016;46(6):452-461. Epub 26 Apr 2016. doi:10.2519/jospt.2016.6279.

A proposed method to investigate reliability throughout a questionnaire.

PubMed

Wentzel-Larsen, Tore; Norekvål, Tone M; Ulvik, Bjørg; Nygård, Ottar; Pripp, Are H

2011-10-05

Questionnaires are used extensively in medical and health care research and depend on validity and reliability. However, participants may differ in interest and awareness throughout long questionnaires, which can affect reliability of their answers. A method is proposed for "screening" of systematic change in random error, which could assess changed reliability of answers. A simulation study was conducted to explore whether systematic change in reliability, expressed as changed random error, could be assessed using unsupervised classification of subjects by cluster analysis (CA) and estimation of intraclass correlation coefficient (ICC). The method was also applied on a clinical dataset from 753 cardiac patients using the Jalowiec Coping Scale. The simulation study showed a relationship between the systematic change in random error throughout a questionnaire and the slope between the estimated ICC for subjects classified by CA and successive items in a questionnaire. This slope was proposed as an awareness measure--to assessing if respondents provide only a random answer or one based on a substantial cognitive effort. Scales from different factor structures of Jalowiec Coping Scale had different effect on this awareness measure. Even though assumptions in the simulation study might be limited compared to real datasets, the approach is promising for assessing systematic change in reliability throughout long questionnaires. Results from a clinical dataset indicated that the awareness measure differed between scales.

Mobile access to virtual randomization for investigator-initiated trials.

PubMed

Deserno, Thomas M; Keszei, András P

2017-08-01

Background/aims Randomization is indispensable in clinical trials in order to provide unbiased treatment allocation and a valid statistical inference. Improper handling of allocation lists can be avoided using central systems, for example, human-based services. However, central systems are unaffordable for investigator-initiated trials and might be inaccessible from some places, where study subjects need allocations. We propose mobile access to virtual randomization, where the randomization lists are non-existent and the appropriate allocation is computed on demand. Methods The core of the system architecture is an electronic data capture system or a clinical trial management system, which is extended by an R interface connecting the R server using the Java R Interface. Mobile devices communicate via the representational state transfer web services. Furthermore, a simple web-based setup allows configuring the appropriate statistics by non-statisticians. Our comprehensive R script supports simple randomization, restricted randomization using a random allocation rule, block randomization, and stratified randomization for un-blinded, single-blinded, and double-blinded trials. For each trial, the electronic data capture system or the clinical trial management system stores the randomization parameters and the subject assignments. Results Apps are provided for iOS and Android and subjects are randomized using smartphones. After logging onto the system, the user selects the trial and the subject, and the allocation number and treatment arm are displayed instantaneously and stored in the core system. So far, 156 subjects have been allocated from mobile devices serving five investigator-initiated trials. Conclusion Transforming pre-printed allocation lists into virtual ones ensures the correct conduct of trials and guarantees a strictly sequential processing in all trial sites. Covering 88% of all randomization models that are used in recent trials, virtual randomization becomes available for investigator-initiated trials and potentially for large multi-center trials.

Strategies and Opportunities to STOP Colon Cancer in Priority Populations: Design of a Cluster-Randomized Pragmatic Trial

PubMed Central

Coronado, Gloria D.; Vollmer, William M.; Petrik, Amanda; Taplin, Stephen H.; Burdick, Timothy E.; Meenan, Richard T.; Green, Beverly

2014-01-01

Background Colorectal cancer is the second-leading cause of cancer deaths in the United States. The Strategies and Opportunities to Stop Colorectal Cancer (STOP CRC) in Priority Populations study is a pragmatic trial and a collaboration between two research institutions and a network of more than 200 safety net clinics. The study will assess effectiveness of a systems-based intervention designed to improve rates of colorectal-cancer screening using fecal immunochemical testing (FIT) in federally qualified health centers in Oregon and Northern California. Material and Methods STOP CRC is a cluster-randomized comparative-effectiveness pragmatic trial enrolling 26 clinics. Clinics will be randomized to one of two arms. Clinics in the intervention arm (1) will use an automated, data-driven, electronic health record-embedded program to identify patients due for colorectal screening and mail FIT kits (with pictographic instructions) to them; (2) will conduct an improvement process (e.g. Plan-Do-Study-Act) to enhance the adoption, reach, and effectiveness of the program. Clinics in the control arm will provide opportunistic colorectal-cancer screening to patients at clinic visits. The primary outcomes are: proportion of age– and screening-eligible patients completing a FIT within 12 months; and cost, cost-effectiveness, and return on investment of the intervention. Conclusions This large-scale pragmatic trial will leverage electronic health record information and existing clinic staff to enroll a broad range of patients, including many with historically low colorectal-cancer screening rates. If successful, the program will provide a model for a cost-effective and scalable method to raise colorectal-cancer screening rates. PMID:24937017

Unsupervised method for automatic construction of a disease dictionary from a large free text collection.

PubMed

Xu, Rong; Supekar, Kaustubh; Morgan, Alex; Das, Amar; Garber, Alan

2008-11-06

Concept specific lexicons (e.g. diseases, drugs, anatomy) are a critical source of background knowledge for many medical language-processing systems. However, the rapid pace of biomedical research and the lack of constraints on usage ensure that such dictionaries are incomplete. Focusing on disease terminology, we have developed an automated, unsupervised, iterative pattern learning approach for constructing a comprehensive medical dictionary of disease terms from randomized clinical trial (RCT) abstracts, and we compared different ranking methods for automatically extracting con-textual patterns and concept terms. When used to identify disease concepts from 100 randomly chosen, manually annotated clinical abstracts, our disease dictionary shows significant performance improvement (F1 increased by 35-88%) over available, manually created disease terminologies.

Unsupervised Method for Automatic Construction of a Disease Dictionary from a Large Free Text Collection

PubMed Central

Xu, Rong; Supekar, Kaustubh; Morgan, Alex; Das, Amar; Garber, Alan

2008-01-01

Concept specific lexicons (e.g. diseases, drugs, anatomy) are a critical source of background knowledge for many medical language-processing systems. However, the rapid pace of biomedical research and the lack of constraints on usage ensure that such dictionaries are incomplete. Focusing on disease terminology, we have developed an automated, unsupervised, iterative pattern learning approach for constructing a comprehensive medical dictionary of disease terms from randomized clinical trial (RCT) abstracts, and we compared different ranking methods for automatically extracting contextual patterns and concept terms. When used to identify disease concepts from 100 randomly chosen, manually annotated clinical abstracts, our disease dictionary shows significant performance improvement (F1 increased by 35–88%) over available, manually created disease terminologies. PMID:18999169

2GETHER - The Dual Protection Project: Design and rationale of a randomized controlled trial to increase dual protection strategy selection and adherence among African American adolescent females

PubMed Central

Ewing, Alexander C.; Kottke, Melissa J.; Kraft, Joan Marie; Sales, Jessica M.; Brown, Jennifer L.; Goedken, Peggy; Wiener, Jeffrey; Kourtis, Athena P.

2018-01-01

Background African American adolescent females are at elevated risk for unintended pregnancy and sexually transmitted infections (STIs). Dual protection (DP) is defined as concurrent prevention of pregnancy and STIs. This can be achieved by abstinence, consistent condom use, or the dual methods of condoms plus an effective non-barrier contraceptive. Previous clinic-based interventions showed short-term effects on increasing dual method use, but evidence of sustained effects on dual method use and decreased incident pregnancies and STIs are lacking. Methods/Design This manuscript describes the 2GETHER Project. 2GETHER is a randomized controlled trial of a multi-component intervention to increase dual protection use among sexually active African American females aged 14–19 years not desiring pregnancy at a Title X clinic in Atlanta, GA. The intervention is clinic-based and includes a culturally tailored interactive multimedia component and counseling sessions, both to assist in selection of a DP method and to reinforce use of the DP method. The participants are randomized to the study intervention or the standard of care, and followed for 12 months to evaluate how the intervention influences DP method selection and adherence, pregnancy and STI incidence, and participants’ DP knowledge, intentions, and self-efficacy. Discussion The 2GETHER Project is a novel trial to reduce unintended pregnancies and STIs among African American adolescents. The intervention is unique in the comprehensive and complementary nature of its components and its individual tailoring of provider-patient interaction. If the trial interventions are shown to be effective, then it will be reasonable to assess their scalability and applicability in other populations. PMID:28007634

Double versus single cervical cerclage for patients with recurrent pregnancy loss: a randomized clinical trial.

PubMed

Zolghadri, Jaleh; Younesi, Masoumeh; Asadi, Nasrin; Khosravi, Dezire; Behdin, Shabnam; Tavana, Zohre; Ghaffarpasand, Fariborz

2014-02-01

To compare the effectiveness of the double cervical cerclage method versus the single method in women with recurrent second-trimester delivery. In this randomized clinical trial, we included 33 singleton pregnancies suffering from recurrent second-trimester pregnancy loss (≥2 consecutive fetal loss during second-trimester or with a history of unsuccessful procedures utilizing the McDonald method), due to cervical incompetence. Patients were randomly assigned to undergo either the classic McDonald method (n = 14) or the double cerclage method (n = 19). The successful pregnancy rate and gestational age at delivery was also compared between the two groups. The two study groups were comparable regarding their baseline characteristics. The successful pregnancy rate did not differ significantly between those who underwent the double cerclage method or the classic McDonald cerclage method (100% vs 85.7%; P = 0.172). In the same way, the preterm delivery rate (<34 weeks of gestation) was comparable between the two study groups (10.5% vs 35.7%; P = 0.106). Those undergoing the double cerclage method had longer gestational duration (37.2 ± 2.6 vs 34.3 ± 3.8 weeks; P = 0.016). The double cervical cerclage method seems to provide better cervical support, as compared with the classic McDonald cerclage method, in those suffering from recurrent pregnancy loss, due to cervical incompetence. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

A novel approach to assess the treatment response using Gaussian random field in PET

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

Wang, Mengdie; Guo, Ning; Hu, Guangshu

2016-02-15

Purpose: The assessment of early therapeutic response to anticancer therapy is vital for treatment planning and patient management in clinic. With the development of personal treatment plan, the early treatment response, especially before any anatomically apparent changes after treatment, becomes urgent need in clinic. Positron emission tomography (PET) imaging serves an important role in clinical oncology for tumor detection, staging, and therapy response assessment. Many studies on therapy response involve interpretation of differences between two PET images, usually in terms of standardized uptake values (SUVs). However, the quantitative accuracy of this measurement is limited. This work proposes a statistically robustmore » approach for therapy response assessment based on Gaussian random field (GRF) to provide a statistically more meaningful scale to evaluate therapy effects. Methods: The authors propose a new criterion for therapeutic assessment by incorporating image noise into traditional SUV method. An analytical method based on the approximate expressions of the Fisher information matrix was applied to model the variance of individual pixels in reconstructed images. A zero mean unit variance GRF under the null hypothesis (no response to therapy) was obtained by normalizing each pixel of the post-therapy image with the mean and standard deviation of the pretherapy image. The performance of the proposed method was evaluated by Monte Carlo simulation, where XCAT phantoms (128{sup 2} pixels) with lesions of various diameters (2–6 mm), multiple tumor-to-background contrasts (3–10), and different changes in intensity (6.25%–30%) were used. The receiver operating characteristic curves and the corresponding areas under the curve were computed for both the proposed method and the traditional methods whose figure of merit is the percentage change of SUVs. The formula for the false positive rate (FPR) estimation was developed for the proposed therapy response assessment utilizing local average method based on random field. The accuracy of the estimation was validated in terms of Euler distance and correlation coefficient. Results: It is shown that the performance of therapy response assessment is significantly improved by the introduction of variance with a higher area under the curve (97.3%) than SUVmean (91.4%) and SUVmax (82.0%). In addition, the FPR estimation serves as a good prediction for the specificity of the proposed method, consistent with simulation outcome with ∼1 correlation coefficient. Conclusions: In this work, the authors developed a method to evaluate therapy response from PET images, which were modeled as Gaussian random field. The digital phantom simulations demonstrated that the proposed method achieved a large reduction in statistical variability through incorporating knowledge of the variance of the original Gaussian random field. The proposed method has the potential to enable prediction of early treatment response and shows promise for application to clinical practice. In future work, the authors will report on the robustness of the estimation theory for application to clinical practice of therapy response evaluation, which pertains to binary discrimination tasks at a fixed location in the image such as detection of small and weak lesion.« less

An Introduction to Recursive Partitioning: Rationale, Application, and Characteristics of Classification and Regression Trees, Bagging, and Random Forests

ERIC Educational Resources Information Center

Strobl, Carolin; Malley, James; Tutz, Gerhard

2009-01-01

Recursive partitioning methods have become popular and widely used tools for nonparametric regression and classification in many scientific fields. Especially random forests, which can deal with large numbers of predictor variables even in the presence of complex interactions, have been applied successfully in genetics, clinical medicine, and…

Randomized Clinical Trial of Cognitive Behavioral Therapy (CBT) versus Acceptance and Commitment Therapy (ACT) for Mixed Anxiety Disorders

ERIC Educational Resources Information Center

Arch, Joanna J.; Eifert, Georg H.; Davies, Carolyn; Vilardaga, Jennifer C. Plumb; Rose, Raphael D.; Craske, Michelle G.

2012-01-01

Objective: Randomized comparisons of acceptance-based treatments with traditional cognitive behavioral therapy (CBT) for anxiety disorders are lacking. To address this gap, we compared acceptance and commitment therapy (ACT) to CBT for heterogeneous anxiety disorders. Method: One hundred twenty-eight individuals (52% female, mean age = 38, 33%…

The Effectiveness of Two Grammar Treatment Procedures for Children with SLI: A Randomized Clinical Trial

ERIC Educational Resources Information Center

Smith-Lock, Karen M.; Leitão, Suze; Prior, Polly; Nickels, Lyndsey

2015-01-01

Purpose: This study compared the effectiveness of two grammar treatment procedures for children with specific language impairment. Method: A double-blind superiority trial with cluster randomization was used to compare a cueing procedure, designed to elicit a correct production following an initial error, to a recasting procedure, which required…

Treatment of Co-Occurring Substance Abuse and Suicidality among Adolescents: A Randomized Trial

ERIC Educational Resources Information Center

Esposito-Smythers, Christianne; Spirito, Anthony; Kahler, Christopher W.; Hunt, Jeffrey; Monti, Peter

2011-01-01

Objective: This study tested a cognitive-behavioral treatment protocol for adolescents with a co-occurring alcohol or other drug use disorder (AOD) and suicidality in a randomized clinical trial. Method: Forty adolescents (M[subscript age] = 15 years; 68% female, 89% White) and their families recruited from an inpatient psychiatric hospital were…

Brief Strategic Family Therapy versus Treatment as Usual: Results of a Multisite Randomized Trial for Substance Using Adolescents

ERIC Educational Resources Information Center

Robbins, Michael S.; Feaster, Daniel J.; Horigian, Viviana E.; Rohrbaugh, Michael; Shoham, Varda; Bachrach, Ken; Miller, Michael; Burlew, Kathleen A.; Hodgkins, Candy; Carrion, Ibis; Vandermark, Nancy; Schindler, Eric; Werstlein, Robert; Szapocznik, Jose

2011-01-01

Objective: To determine the effectiveness of brief strategic family therapy (BSFT; an evidence-based family therapy) compared to treatment as usual (TAU) as provided in community-based adolescent outpatient drug abuse programs. Method: A randomized effectiveness trial in the National Drug Abuse Treatment Clinical Trials Network compared BSFT to…

Cancer Screening Knowledge Changes: Results from a Randomized Control Trial of Women with Developmental Disabilities

ERIC Educational Resources Information Center

Parish, Susan L.; Rose, Roderick A.; Luken, Karen; Swaine, Jamie G.; O'Hare, Lindsey

2012-01-01

Background: Women with developmental disabilities are much less likely than nondisabled women to receive cervical and breast cancer screening according to clinical guidelines. One barrier to receipt of screenings is a lack of knowledge about preventive screenings. Method: To address this barrier, we used a randomized control trial (n = 175 women)…

Cognitive Behavioral Therapy for 4- to 7-Year-Old Children with Anxiety Disorders: A Randomized Clinical Trial

ERIC Educational Resources Information Center

Hirshfeld-Becker, Dina R.; Masek, Bruce; Henin, Aude; Blakely, Lauren Raezer; Pollock-Wurman, Rachel A.; McQuade, Julia; DePetrillo, Lillian; Briesch, Jacquelyn; Ollendick, Thomas H.; Rosenbaum, Jerrold F.; Biederman, Joseph

2010-01-01

Objective: To examine the efficacy of a developmentally appropriate parent-child cognitive behavioral therapy (CBT) protocol for anxiety disorders in children ages 4-7 years. Method: Design: Randomized wait-list controlled trial. Conduct: Sixty-four children (53% female, mean age 5.4 years, 80% European American) with anxiety disorders were…

Reducing Sexual Risk Behaviors for HIV/STDs in Women with Alcohol Use Disorders

ERIC Educational Resources Information Center

Langhorst, Diane M.; Choi, Y. Joon; Keyser-Marcus, Lori; Svikis, Dace S.

2012-01-01

Objective: A pilot randomized clinical trial (RCT) examined effectiveness of HIV/STD Safer Sex Skills Building + Alcohol (SSB+A) intervention for women with Alcohol Use Disorders (AUDs) in a residential treatment setting. Method: After randomizing thirty-six women with AUDs and reporting having intercourse with a male partner in the past 180 days…

[Methodologies of publications in the Revista de Investigación Clínica during the last 20 years].

PubMed

López-Jiménez, F; Borovoy, J

1997-01-01

To characterize the clinical research methods published in the Revista de Investigación Clínica for the past 20 years. Comparative study of methods used in the RIC articles published in 3-years periods representing three decades (1972-74, 1982-84, 1992-94). Out of 273 original papers, 218 (80%) were of clinical research. There was an increased percentage of longitudinal vs cross-sectional studies, with cohort and randomized clinical trials showing the largest increase. The total number of research manuscripts also increased. The clinical research methods of the papers in the RIC have shown an increased rate of designs with a higher scientific value.

A quantitative and qualitative evaluation of reports of clinical trials published in six Brazilian dental journals indexed in the Scientific Electronic Library Online (SciELO)

PubMed Central

de SOUZA, Raphael Freitas; CHAVES, Carolina de Andrade Lima; CHAVES, Carolina de Andrade Lima; CHAVES, Carolina de Andrade Lima; NASSER, Mona; FEDOROWICZ, Zbys

2010-01-01

Open access publishing is becoming increasingly popular within the biomedical sciences. SciELO, the Scientific Electronic Library Online, is a digital library covering a selected collection of Brazilian scientific journals many of which provide open access to full-text articles. This library includes a number of dental journals some of which may include reports of clinical trials in English, Portuguese and/or Spanish. Thus, SciELO could play an important role as a source of evidence for dental healthcare interventions especially if it yields a sizeable number of high quality reports. Objective The aim of this study was to identify reports of clinical trials by handsearching of dental journals that are accessible through SciELO, and to assess the overall quality of these reports. Material and methods Electronic versions of six Brazilian dental Journals indexed in SciELO were handsearched at www.scielo.br in September 2008. Reports of clinical trials were identified and classified as controlled clinical trials (CCTs - prospective, experimental studies comparing 2 or more healthcare interventions in human beings) or randomized controlled trials (RCTs - a random allocation method is clearly reported), according to Cochrane eligibility criteria. Criteria to assess methodological quality included: method of randomization, concealment of treatment allocation, blinded outcome assessment, handling of withdrawals and losses and whether an intention-totreat analysis had been carried out. Results The search retrieved 33 CCTs and 43 RCTs. A majority of the reports provided no description of either the method of randomization (75.3%) or concealment of the allocation sequence (84.2%). Participants and outcome assessors were reported as blinded in only 31.2% of the reports. Withdrawals and losses were only clearly described in 6.5% of the reports and none mentioned an intention-totreat analysis or any similar procedure. Conclusions The results of this study indicate that a substantial number of reports of trials and systematic reviews are available in the dental journals listed in SciELO, and that these could provide valuable evidence for clinical decision making. However, it is clear that the quality of a number of these reports is of some concern and that improvement in the conduct and reporting of these trials could be achieved if authors adhered to internationally accepted guidelines, e.g. the CONSORT statement. PMID:20485919

Optimal dose selection accounting for patient subpopulations in a randomized Phase II trial to maximize the success probability of a subsequent Phase III trial.

PubMed

Takahashi, Fumihiro; Morita, Satoshi

2018-02-08

Phase II clinical trials are conducted to determine the optimal dose of the study drug for use in Phase III clinical trials while also balancing efficacy and safety. In conducting these trials, it may be important to consider subpopulations of patients grouped by background factors such as drug metabolism and kidney and liver function. Determining the optimal dose, as well as maximizing the effectiveness of the study drug by analyzing patient subpopulations, requires a complex decision-making process. In extreme cases, drug development has to be terminated due to inadequate efficacy or severe toxicity. Such a decision may be based on a particular subpopulation. We propose a Bayesian utility approach (BUART) to randomized Phase II clinical trials which uses a first-order bivariate normal dynamic linear model for efficacy and safety in order to determine the optimal dose and study population in a subsequent Phase III clinical trial. We carried out a simulation study under a wide range of clinical scenarios to evaluate the performance of the proposed method in comparison with a conventional method separately analyzing efficacy and safety in each patient population. The proposed method showed more favorable operating characteristics in determining the optimal population and dose.

“Entering a Clinical Trial: Is it Right For You?"-- A Randomized Study of The Clinical Trials Video and Its Impact on the Informed Consent Process

PubMed Central

Hoffner, Brianna; Bauer-Wu, Susan; Hitchcock-Bryan, Suzanne; Powell, Mark; Wolanski, Andrew; Joffe, Steven

2011-01-01

PURPOSE This randomized study was designed to assess the utility of an educational video in preparing cancer patients for decisions about clinical trial participation. The study assessed the effect of the video on patients’ understanding and perceptions of clinical trials, its impact on decision making and patient-provider communication, and patients’ satisfaction with the video. METHODS Ninety adults considering cancer clinical trials were randomized to receive (n=45) or not receive (n=45) the video. Using the validated Quality of Informed Consent (QuIC), respondents’ knowledge about clinical trial participation was assessed. All subjects completed additional questions about satisfaction with the video, decision making, and patient-provider communication. Data were analyzed using the Wilcoxon rank-sum test, regression model and descriptive statistics. RESULTS Although intent-to-treat analysis found no significant group differences in objective understanding between those randomized to view or not view the video, the majority of participants reported favorable experiences with regard to watching the video: 85% found the video was an important source of information about clinical trials; 81% felt better prepared to discuss the trial with their physician; 89% of those who watched the video with family indicated that it helped family better understand clinical trials; and 73% indicated it helped family accept their decision about participation. CONCLUSIONS Although the video did not measurably improve patients’ knowledge about clinical trials, it was an important source of information, helped educate families, and enhanced patient communication with their oncology providers. PMID:22009665

Design of the multicenter standardized supervised exercise training intervention for the claudication: exercise vs endoluminal revascularization (CLEVER) study.

PubMed

Bronas, Ulf G; Hirsch, Alan T; Murphy, Timothy; Badenhop, Dalynn; Collins, Tracie C; Ehrman, Jonathan K; Ershow, Abby G; Lewis, Beth; Treat-Jacobson, Diane J; Walsh, M Eileen; Oldenburg, Niki; Regensteiner, Judith G

2009-11-01

The CLaudication: Exercise Vs Endoluminal Revascularization (CLEVER) study is the first randomized, controlled, clinical, multicenter trial that is evaluating a supervised exercise program compared with revascularization procedures to treat claudication. In this report, the methods and dissemination techniques of the supervised exercise training intervention are described. A total of 217 participants are being recruited and randomized to one of three arms: (1) optimal medical care; (2) aortoiliac revascularization with stent; or (3) supervised exercise training. Of the enrolled patients, 84 will receive supervised exercise therapy. Supervised exercise will be administered according to a protocol designed by a central CLEVER exercise training committee based on validated methods previously used in single center randomized control trials. The protocol will be implemented at each site by an exercise committee member using training methods developed and standardized by the exercise training committee. The exercise training committee reviews progress and compliance with the protocol of each participant weekly. In conclusion, a multicenter approach to disseminate the supervised exercise training technique and to evaluate its efficacy, safety and cost-effectiveness for patients with claudication due to peripheral arterial disease (PAD) is being evaluated for the first time in CLEVER. The CLEVER study will further establish the role of supervised exercise training in the treatment of claudication resulting from PAD and provide standardized methods for use of supervised exercise training in future PAD clinical trials as well as in clinical practice.

Reference-free error estimation for multiple measurement methods.

PubMed

Madan, Hennadii; Pernuš, Franjo; Špiclin, Žiga

2018-01-01

We present a computational framework to select the most accurate and precise method of measurement of a certain quantity, when there is no access to the true value of the measurand. A typical use case is when several image analysis methods are applied to measure the value of a particular quantitative imaging biomarker from the same images. The accuracy of each measurement method is characterized by systematic error (bias), which is modeled as a polynomial in true values of measurand, and the precision as random error modeled with a Gaussian random variable. In contrast to previous works, the random errors are modeled jointly across all methods, thereby enabling the framework to analyze measurement methods based on similar principles, which may have correlated random errors. Furthermore, the posterior distribution of the error model parameters is estimated from samples obtained by Markov chain Monte-Carlo and analyzed to estimate the parameter values and the unknown true values of the measurand. The framework was validated on six synthetic and one clinical dataset containing measurements of total lesion load, a biomarker of neurodegenerative diseases, which was obtained with four automatic methods by analyzing brain magnetic resonance images. The estimates of bias and random error were in a good agreement with the corresponding least squares regression estimates against a reference.

A random walk model for evaluating clinical trials involving serial observations.

PubMed

Hopper, J L; Young, G P

1988-05-01

For clinical trials where the variable of interest is ordered and categorical (for example, disease severity, symptom scale), and where measurements are taken at intervals, it might be possible to achieve a greater discrimination between the efficacy of treatments by modelling each patient's progress as a stochastic process. The random walk is a simple, easily interpreted model that can be fitted by maximum likelihood using a maximization routine with inference based on standard likelihood theory. In general the model can allow for randomly censored data, incorporates measured prognostic factors, and inference is conditional on the (possibly non-random) allocation of patients. Tests of fit and of model assumptions are proposed, and application to two therapeutic trials of gastroenterological disorders are presented. The model gave measures of the rate of, and variability in, improvement for patients under different treatments. A small simulation study suggested that the model is more powerful than considering the difference between initial and final scores, even when applied to data generated by a mechanism other than the random walk model assumed in the analysis. It thus provides a useful additional statistical method for evaluating clinical trials.

The Prevention of Hemorrhagic Stroke

PubMed Central

Raymond, J.; Mohr, JP; the TEAM-ARUBA collaborative groups

2008-01-01

Summary There is currently no evidence that preventive treatment of unruptured aneurysms or AVMs is beneficial and randomized trials have been proposed to address this clinical uncertainty. Participation in a trial may necessitate a shift of point of view compared to a certain habitual clinical mentality. A review of the ethical and rational principles governing the design and realization of a trial may help integrate clinical research into expert clinical practices. The treatment of unruptured aneurysms and AVMs remains controversial, and data from observational studies cannot provide a normative basis for clinical decisions. Prevention targets healthy individuals and hence has an obligation of results. There is no opposition between the search for objective facts using scientific methods and the ethics of medical practice since a good practice cannot forbid physicians the means to define what could be beneficial to patients. Perhaps the most difficult task is to recognize the uncertainty that is crucial to allow resorting to trial methodology. The reasoning that is used in research and analysis differs from the casuistic methods typical of clinical work, but clinical judgement remains the dominant factor that decides both who enters the trial and to whom the results of the trial will apply. Randomization is still perceived as a difficult and strange method to integrate into normal practice, but in the face of uncertainty it assures the best chances for the best outcome to each participant. Some tension exists between scientific methods and normal practice, but they need to coexist if we are to progress at the same time we care for patients. PMID:20557736

An observational study showed that explaining randomization using gambling-related metaphors and computer-agency descriptions impeded randomized clinical trial recruitment.

PubMed

Jepson, Marcus; Elliott, Daisy; Conefrey, Carmel; Wade, Julia; Rooshenas, Leila; Wilson, Caroline; Beard, David; Blazeby, Jane M; Birtle, Alison; Halliday, Alison; Stein, Rob; Donovan, Jenny L

2018-07-01

To explore how the concept of randomization is described by clinicians and understood by patients in randomized controlled trials (RCTs) and how it contributes to patient understanding and recruitment. Qualitative analysis of 73 audio recordings of recruitment consultations from five, multicenter, UK-based RCTs with identified or anticipated recruitment difficulties. One in 10 appointments did not include any mention of randomization. Most included a description of the method or process of allocation. Descriptions often made reference to gambling-related metaphors or similes, or referred to allocation by a computer. Where reference was made to a computer, some patients assumed that they would receive the treatment that was "best for them". Descriptions of the rationale for randomization were rarely present and often only came about as a consequence of patients questioning the reason for a random allocation. The methods and processes of randomization were usually described by recruiters, but often without clarity, which could lead to patient misunderstanding. The rationale for randomization was rarely mentioned. Recruiters should avoid problematic gambling metaphors and illusions of agency in their explanations and instead focus on clearer descriptions of the rationale and method of randomization to ensure patients are better informed about randomization and RCT participation. Copyright © 2018 University of Bristol. Published by Elsevier Inc. All rights reserved.

Impact of clinical pharmacist-based parenteral nutrition service for bone marrow transplantation patients: a randomized clinical trial.

PubMed

Mousavi, Maryam; Hayatshahi, Alireza; Sarayani, Amir; Hadjibabaie, Molouk; Javadi, Mohammadreza; Torkamandi, Hassan; Gholami, Kheirollah; Ghavamzadeh, Ardeshir

2013-12-01

Parenteral nutrition (PN) is a well-documented supportive care which maintains the nutritional status of patients. Clinical pharmacists are often involved in providing PN services; however, few studies have investigated the effect of a clinical pharmacy-based PN service in resource-limited settings. We designed a randomized clinical trial to compare the clinical pharmacist-based PN service (intervention group) with the conventional method (control group) for adult patients undergoing hematopoietic stem cell transplantation in Shariati Hospital, Tehran, Iran (2011-2012). In the intervention group, the clinical pharmacists implemented standard guidelines of nutrition support. The conventional method was a routine nutrition support protocol which was pursued for all patients in the bone marrow transplantation wards. Main study outcomes included nutritional status (weight, albumin, total protein, pre-albumin, and nitrogen balance), length of hospital stay, time to engraftment, rate of graft versus host disease, and mortality rate. Patients were followed for 3 months. Fifty-nine patients were randomly allocated to a study group. The overall intake (oral and parenteral) in the control group was significantly lower than standard daily needed calories (P < 0.01). Patients in the intervention group received fewer days of PN (10.7 ± 4.2 vs. 18.4 ± 5.5 days, P < 0.01). All nutritional outcomes were either preserved or improved in the intervention group while the nutritional status in the control group was deteriorated (P values < 0.01). Length of hospital stay was significantly shorter in the intervention group (P < 0.01). Regarding PN complications, hyperglycemia was observed more frequently in the intervention group (34.5 %, P = 0.01). Two patients in the control group expired due to graft versus host disease at the 3-month follow-up. A clinical pharmacist-based nutrition support service significantly improved nutritional status and clinical outcomes in comparison with the suboptimal conventional method. Future studies should assess the cost effectiveness of clinical pharmacists' PN services.

Randomization in clinical trials: stratification or minimization? The HERMES free simulation software.

PubMed

Fron Chabouis, Hélène; Chabouis, Francis; Gillaizeau, Florence; Durieux, Pierre; Chatellier, Gilles; Ruse, N Dorin; Attal, Jean-Pierre

2014-01-01

Operative clinical trials are often small and open-label. Randomization is therefore very important. Stratification and minimization are two randomization options in such trials. The first aim of this study was to compare stratification and minimization in terms of predictability and balance in order to help investigators choose the most appropriate allocation method. Our second aim was to evaluate the influence of various parameters on the performance of these techniques. The created software generated patients according to chosen trial parameters (e.g., number of important prognostic factors, number of operators or centers, etc.) and computed predictability and balance indicators for several stratification and minimization methods over a given number of simulations. Block size and proportion of random allocations could be chosen. A reference trial was chosen (50 patients, 1 prognostic factor, and 2 operators) and eight other trials derived from this reference trial were modeled. Predictability and balance indicators were calculated from 10,000 simulations per trial. Minimization performed better with complex trials (e.g., smaller sample size, increasing number of prognostic factors, and operators); stratification imbalance increased when the number of strata increased. An inverse correlation between imbalance and predictability was observed. A compromise between predictability and imbalance still has to be found by the investigator but our software (HERMES) gives concrete reasons for choosing between stratification and minimization; it can be downloaded free of charge. This software will help investigators choose the appropriate randomization method in future two-arm trials.

The case for randomized controlled trials to assess the impact of clinical information systems.

PubMed

Liu, Joseph L Y; Wyatt, Jeremy C

2011-01-01

There is a persistent view of a significant minority in the medical informatics community that the randomized controlled trial (RCT) has a limited role to play in evaluating clinical information systems. A common reason voiced by skeptics is that these systems are fundamentally different from drug interventions, so the RCT is irrelevant. There is an urgent need to promote the use of RCTs, given the shift to evidence-based policy and the need to demonstrate cost-effectiveness of these systems. The authors suggest returning to first principles and argue that what is required is clarity about how to match methods to evaluation questions. The authors address common concerns about RCTs, and the extent to which they are fallacious, and also discuss the challenges of conducting RCTs in informatics and alternative study designs when randomized trials are infeasible. While neither a perfect nor universal evaluation method, RCTs form an important part of an evaluator's toolkit.

The case for randomized controlled trials to assess the impact of clinical information systems

PubMed Central

Wyatt, Jeremy C

2011-01-01

There is a persistent view of a significant minority in the medical informatics community that the randomized controlled trial (RCT) has a limited role to play in evaluating clinical information systems. A common reason voiced by skeptics is that these systems are fundamentally different from drug interventions, so the RCT is irrelevant. There is an urgent need to promote the use of RCTs, given the shift to evidence-based policy and the need to demonstrate cost-effectiveness of these systems. The authors suggest returning to first principles and argue that what is required is clarity about how to match methods to evaluation questions. The authors address common concerns about RCTs, and the extent to which they are fallacious, and also discuss the challenges of conducting RCTs in informatics and alternative study designs when randomized trials are infeasible. While neither a perfect nor universal evaluation method, RCTs form an important part of an evaluator's toolkit. PMID:21270132

Methodological and ethical aspects of randomized controlled clinical trials in minors with malignant diseases.

PubMed

Rothenberger, Lillian G; Henschel, Andreas Dirk; Schrey, Dominik; Becker, Andreas; Boos, Joachim

2011-10-01

Due to the new European regulations for pediatric medications, future clinical trials will include an increasing number of minors. It is therefore important to reconsider and evaluate recent methodological and ethical aspects of clinical trials in minors. The following questions were investigated: How are randomized controlled clinical trials (RCTs) performed in practice? Do investigators take into consideration biomedical ethical principles, explicated for example by Beauchamp and Childress, when planning and conducting a trial? The study was conducted in a descriptive manner. A systematic, algorithm-guided search focusing on RCTs in minors with malignant diseases was carried out in PubMed. One-thousand-nine-hundred-sixty-two publications from 2001 to 2005 were randomized in sequence. The first 1,000 publications were screened according to a priori defined inclusion criteria. One hundred seventy-five publications met the criteria and were reviewed using the SIGN methodological checklist (2004), the CONSORT Statement (2001, section Methods, items 3-12) and indicators for ethical aspects. Seventeen publications were checked by two raters. Information on randomization and blinding was often equivocal. The publications were mainly rated positive for the criteria of the SIGN checklist, and mostly rated negative for the additional items of the CONSORT Statement. Regarding the ethical principles, only few contributions were found in the publications. Inter-rater reliability was good. In the publications analyzed, we found only limited information concerning methods and reflections on ethical principles of the trials. Improvements are thus necessary and possible. We suggest how such trials and their respective publications can be optimized for these aspects. Copyright © 2011 Wiley-Liss, Inc.

Randomized trials published in some Chinese journals: how many are randomized?

PubMed

Wu, Taixiang; Li, Youping; Bian, Zhaoxiang; Liu, Guanjian; Moher, David

2009-07-02

The approximately 1100 medical journals now active in China are publishing a rapidly increasing number of research reports, including many studies identified by their authors as randomized controlled trials. It has been noticed that these reports mostly present positive results, and their quality and authenticity have consequently been called into question. We investigated the adequacy of randomization of clinical trials published in recent years in China to determine how many of them met acceptable standards for allocating participants to treatment groups. The China National Knowledge Infrastructure electronic database was searched for reports of randomized controlled trials on 20 common diseases published from January 1994 to June 2005. From this sample, a subset of trials that appeared to have used randomization methods was selected. Twenty-one investigators trained in the relevant knowledge, communication skills and quality control issues interviewed the original authors of these trials about the participant randomization methods and related quality-control features of their trials. From an initial sample of 37,313 articles identified in the China National Knowledge Infrastructure database, we found 3137 apparent randomized controlled trials. Of these, 1452 were studies of conventional medicine (published in 411 journals) and 1685 were studies of traditional Chinese medicine (published in 352 journals). Interviews with the authors of 2235 of these reports revealed that only 207 studies adhered to accepted methodology for randomization and could on those grounds be deemed authentic randomized controlled trials (6.8%, 95% confidence interval 5.9-7.7). There was no statistically significant difference in the rate of authenticity between randomized controlled trials of traditional interventions and those of conventional interventions. Randomized controlled trials conducted at hospitals affiliated to medical universities were more likely to be authentic than trials conducted at level 3 and level 2 hospitals (relative risk 1.58, 95% confidence interval 1.18-2.13, and relative risk 14.42, 95% confidence interval 9.40-22.10, respectively). The likelihood of authenticity was higher in level 3 hospitals than in level 2 hospitals (relative risk 9.32, 95% confidence interval 5.83-14.89). All randomized controlled trials of pre-market drug clinical trial were authentic by our criteria. Of the trials conducted at university-affiliated hospitals, 56.3% were authentic (95% confidence interval 32.0-81.0). Most reports of randomized controlled trials published in some Chinese journals lacked an adequate description of randomization. Similarly, most so called 'randomized controlled trials' were not real randomized controlled trials owing to a lack of adequate understanding on the part of the authors of rigorous clinical trial design. All randomized controlled trials of pre-market drug clinical trial included in this research were authentic. Randomized controlled trials conducted by authors in high level hospitals, especially in hospitals affiliated to medical universities had a higher rate of authenticity. That so many non-randomized controlled trials were published as randomized controlled trials reflected the fact that peer review needs to be improved and a good practice guide for peer review including how to identify the authenticity of the study urgently needs to be developed.

Transcutaneous bilirubinometry reduces the need for blood sampling in neonates with visible jaundice.

PubMed

Mishra, S; Chawla, D; Agarwal, R; Deorari, A K; Paul, V K; Bhutani, V K

2009-12-01

We determined usefulness of transcutaneous bilirubinometry to decrease the need for blood sampling to assay serum total bilirubin (STB) in the management of jaundiced healthy Indian neonates. Newborns, > or =35 weeks' gestation, with clinical evidence of jaundice were enrolled in an institutional approved randomized clinical trial. The severity of hyperbilirubinaemia was determined by two non-invasive methods: i) protocol-based visual assessment of bilirubin (VaB) and ii) transcutaneous bilirubin (TcB) determination (BiliCheck). By a random allocation, either method was used to decide the need for blood sampling, which was defined to be present if assessed STB by allocated method exceeded 80% of hour-specific threshold values for phototherapy (2004 AAP Guidelines). A total of 617 neonates were randomized to either TcB (n = 314) or VaB (n = 303) groups with comparable gestation, birth weight and postnatal age. Need for blood sampling to assay STB was 34% lower (95% CI: 10% to 51%) in the TcB group compared with VaB group (17.5% vs 26.4% assessments; risk difference: -8.9%, 95% CI: -2.4% to -15.4%; p = 0.008). Routine use of transcutaneous bilirubinometry compared with systematic visual assessment of bilirubin significantly reduced the need for blood sampling to assay STB in jaundiced term and late-preterm neonates. (ClinicalTrials.gov number, NCT00653874).

Effectiveness of the Dader Method for pharmaceutical care in patients with bipolar I disorder: EMDADER-TAB: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Bipolar I disorder (BD-I) is a chronic mental illness characterized by the presence of one or more manic episodes, or both depressive and manic episodes, usually separated by asymptomatic intervals. Pharmacists can contribute to the management of BD-I, mainly with the use of effective and safe drugs, and improve the patient’s life quality through pharmaceutical care. Some studies have shown the effect of pharmaceutical care in the achievement of therapeutic goals in different illnesses; however, to our knowledge, there is a lack of randomized controlled trials designed to assess the effect of pharmacist intervention in patients with BD. The aim of this study is to assess the effectiveness of the Dader Method for pharmaceutical care in patients with BD-I. Methods/design Randomized, controlled, prospective, single-center clinical trial with duration of 12 months will be performed to compare the effect of Dader Method of pharmaceutical care with the usual care process of patients in a psychiatric clinic. Patients diagnosed with BD-I aged between 18 and 65 years who have been discharged or referred from outpatients service of the San Juan de Dios Clinic (Antioquia, Colombia) will be included. Patients will be randomized into the intervention group who will receive pharmaceutical care provided by pharmacists working in collaboration with psychiatrists, or into the control group who will receive usual care and verbal-written counseling regarding BD. Study outcomes will be assessed at baseline and at 3, 6, 9, and 12 months after randomization. The primary outcome will be to measure the number of hospitalizations, emergency service consultations, and unscheduled outpatient visits. Effectiveness, safety, adherence, and quality of life will be assessed as secondary outcomes. Statistical analyses will be performed using two-tailed McNemar tests, Pearson chi-square tests, and Student’s t-tests; a P value <0.05 will be considered as statistically significant. Discussion As far as we know, this is the first randomized controlled trial to assess the effect of the Dader Method for pharmaceutical care in patients with BD-I and it could generate valuable information and recommendations about the role of pharmacists in the improvement of therapeutic goals, solution of drug-related problems, and adherence. Trial registration Registration number NCT01750255 on August 6, 2012. First patient randomized on 24 November 2011. PMID:24885673

2GETHER - The Dual Protection Project: Design and rationale of a randomized controlled trial to increase dual protection strategy selection and adherence among African American adolescent females.

PubMed

Ewing, Alexander C; Kottke, Melissa J; Kraft, Joan Marie; Sales, Jessica M; Brown, Jennifer L; Goedken, Peggy; Wiener, Jeffrey; Kourtis, Athena P

2017-03-01

African American adolescent females are at elevated risk for unintended pregnancy and sexually transmitted infections (STIs). Dual protection (DP) is defined as concurrent prevention of pregnancy and STIs. This can be achieved by abstinence, consistent condom use, or the dual methods of condoms plus an effective non-barrier contraceptive. Previous clinic-based interventions showed short-term effects on increasing dual method use, but evidence of sustained effects on dual method use and decreased incident pregnancies and STIs are lacking. This manuscript describes the 2GETHER Project. 2GETHER is a randomized controlled trial of a multi-component intervention to increase dual protection use among sexually active African American females aged 14-19years not desiring pregnancy at a Title X clinic in Atlanta, GA. The intervention is clinic-based and includes a culturally tailored interactive multimedia component and counseling sessions, both to assist in selection of a DP method and to reinforce use of the DP method. The participants are randomized to the study intervention or the standard of care, and followed for 12months to evaluate how the intervention influences DP method selection and adherence, pregnancy and STI incidence, and participants' DP knowledge, intentions, and self-efficacy. The 2GETHER Project is a novel trial to reduce unintended pregnancies and STIs among African American adolescents. The intervention is unique in the comprehensive and complementary nature of its components and its individual tailoring of provider-patient interaction. If the trial interventions are shown to be effective, then it will be reasonable to assess their scalability and applicability in other populations. Published by Elsevier Inc.

A Prospective, Randomized, Double-blind, Split-face Clinical Trial Comparing the Efficacy of Two Topical Human Growth Factors for the Rejuvenation of the Aging Face

PubMed Central

Goldman, Mitchel P.

2017-01-01

Background: Cosmeceutical products represent an increasingly important therapeutic option for anti-aging and rejuvenation, either used alone or in combination with dermatologic surgical procedures. Among this group of products, topical growth factors have demonstrated efficacy in randomized, controlled clinical trials. However, comparisons between different products remain uncommon. Objective: The objective of this randomized, double-blind, split-face clinical trial was to compare two different topical growth factor formulations derived from either human fibroblasts or human adipose tissue derived mesenchymal stem cells. Methods: This was an institutional review board-approved, randomized, double-blind, split-face clinical trial involving 20 healthy subjects with moderate-to-severe facial wrinkling secondary to photodamage. One half of the face was randomized to receive topical human fibroblast growth factors and the other topical human mesenchymal stem cell growth factors. Treatment was continued for three months, and evaluations were performed in a double-blind fashion. Results: Both growth factor formulations achieved significant improvement in facial wrinkling. Blinded investigator and subject evaluations did not detect any significant differences between the two formulations in terms of efficacy, safety, or tolerability. Conclusion: Both human fibroblast growth factors and human mesenchymal stem cell growth factors are effective at facial rejuvenation. Topical growth factors represent a useful therapeutic modality. PMID:28670356

A Prospective, Randomized, Double-blind, Split-face Clinical Trial Comparing the Efficacy of Two Topical Human Growth Factors for the Rejuvenation of the Aging Face.

PubMed

Wu, Douglas C; Goldman, Mitchel P

2017-05-01

Background: Cosmeceutical products represent an increasingly important therapeutic option for anti-aging and rejuvenation, either used alone or in combination with dermatologic surgical procedures. Among this group of products, topical growth factors have demonstrated efficacy in randomized, controlled clinical trials. However, comparisons between different products remain uncommon. Objective: The objective of this randomized, double-blind, split-face clinical trial was to compare two different topical growth factor formulations derived from either human fibroblasts or human adipose tissue derived mesenchymal stem cells. Methods: This was an institutional review board-approved, randomized, double-blind, split-face clinical trial involving 20 healthy subjects with moderate-to-severe facial wrinkling secondary to photodamage. One half of the face was randomized to receive topical human fibroblast growth factors and the other topical human mesenchymal stem cell growth factors. Treatment was continued for three months, and evaluations were performed in a double-blind fashion. Results: Both growth factor formulations achieved significant improvement in facial wrinkling. Blinded investigator and subject evaluations did not detect any significant differences between the two formulations in terms of efficacy, safety, or tolerability. Conclusion: Both human fibroblast growth factors and human mesenchymal stem cell growth factors are effective at facial rejuvenation. Topical growth factors represent a useful therapeutic modality.

Multiple imputation methods for nonparametric inference on cumulative incidence with missing cause of failure

PubMed Central

Lee, Minjung; Dignam, James J.; Han, Junhee

2014-01-01

We propose a nonparametric approach for cumulative incidence estimation when causes of failure are unknown or missing for some subjects. Under the missing at random assumption, we estimate the cumulative incidence function using multiple imputation methods. We develop asymptotic theory for the cumulative incidence estimators obtained from multiple imputation methods. We also discuss how to construct confidence intervals for the cumulative incidence function and perform a test for comparing the cumulative incidence functions in two samples with missing cause of failure. Through simulation studies, we show that the proposed methods perform well. The methods are illustrated with data from a randomized clinical trial in early stage breast cancer. PMID:25043107

Comparison of Digital 12-Lead ECG and Digital 12-Lead Holter ECG Recordings in Healthy Male Subjects: Results from a Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

PubMed

Wang, Duolao; Bakhai, Ameet; Arezina, Radivoj; Täubel, Jörg

2016-11-01

Electrocardiogram (ECG) variability is greatly affected by the ECG recording method. This study aims to compare Holter and standard ECG recording methods in terms of central locations and variations of ECG data. We used the ECG data from a double-blinded, placebo-controlled, randomized clinical trial and used a mixed model approach to assess the agreement between two methods in central locations and variations of eight ECG parameters (Heart Rate, PR, QRS, QT, RR, QTcB, QTcF, and QTcI intervals). A total of 34 heathy male subjects with mean age of 25.7 ± 4.78 years were randomized to receive either active drug or placebo. Digital 12-lead ECG and digital 12-lead Holter ECG recordings were performed to assess ECG variability. There are no significant differences in least square mean between the Holter and the standard method for all ECG parameters. The total variance is consistently higher for the Holter method than the standard method for all ECG parameters except for QRS. The intraclass correlation coefficient (ICC) values for the Holter method are consistently lower than those for the standard method for all ECG parameters except for QRS, in particular, the ICC for QTcF is reduced from 0.86 for the standard method to 0.67 for the Holter method. This study suggests that Holter ECGs recorded in a controlled environment are not significantly different but more variable than those from the standard method. © 2016 Wiley Periodicals, Inc.

Conditional Monte Carlo randomization tests for regression models.

PubMed

Parhat, Parwen; Rosenberger, William F; Diao, Guoqing

2014-08-15

We discuss the computation of randomization tests for clinical trials of two treatments when the primary outcome is based on a regression model. We begin by revisiting the seminal paper of Gail, Tan, and Piantadosi (1988), and then describe a method based on Monte Carlo generation of randomization sequences. The tests based on this Monte Carlo procedure are design based, in that they incorporate the particular randomization procedure used. We discuss permuted block designs, complete randomization, and biased coin designs. We also use a new technique by Plamadeala and Rosenberger (2012) for simple computation of conditional randomization tests. Like Gail, Tan, and Piantadosi, we focus on residuals from generalized linear models and martingale residuals from survival models. Such techniques do not apply to longitudinal data analysis, and we introduce a method for computation of randomization tests based on the predicted rate of change from a generalized linear mixed model when outcomes are longitudinal. We show, by simulation, that these randomization tests preserve the size and power well under model misspecification. Copyright © 2014 John Wiley & Sons, Ltd.

Effects of a Psychological Intervention in a Primary Health Care Center for Caregivers of Dependent Relatives: A Randomized Trial

ERIC Educational Resources Information Center

Rodriguez-Sanchez, Emiliano; Patino-Alonso, Maria C.; Mora-Simon, Sara; Gomez-Marcos, Manuel A.; Perez-Penaranda, Anibal; Losada-Baltar, Andres; Garcia-Ortiz, Luis

2013-01-01

Purpose: To assess, in the context of Primary Health Care (PHC), the effect of a psychological intervention in mental health among caregivers (CGs) of dependent relatives. Design and Methods: Randomized multicenter, controlled clinical trial. The 125 CGs included in the trial were receiving health care in PHC. Inclusion criteria: Identifying…

Randomized Controlled Trial of Problem-Solving Therapy for Minor Depression in Home Care

ERIC Educational Resources Information Center

Gellis, Zvi D.; McGinty, Jean; Tierney, Lynda; Jordan, Cindy; Burton, Jean; Misener, Elizabeth

2008-01-01

Objective: Data are presented from a pilot research program initiated to develop, refine, and test the outcomes of problem-solving therapy that targets the needs of older adults with minor depression in home care settings. Method: A pilot randomized clinical trial compares the impact of problem-solving therapy for home care to treatment as usual…

Stepped and Standard Care for Childhood Trauma: A Pilot Randomized Clinical Trial

ERIC Educational Resources Information Center

Salloum, Alison; Small, Brent J.; Robst, John; Scheeringa, Michael S.; Cohen, Judith A.; Storch, Eric A.

2017-01-01

Objective: This study explored the feasibility of stepped care trauma-focused cognitive behavioral therapy (SC-TF-CBT) relative to TF-CBT with children (aged 8--12). Method: Children (N = 33) with post-traumatic stress symptoms (PTSS) were randomly assigned (2:1) to SC-TF-CBT or TF-CBT. SC-TF-CBT consisted of Step 1, parent-led therapist-assisted…

Safety and Efficacy of ABT-089 in Pediatric Attention-Deficit/Hyperactivity Disorder: Results from Two Randomized Placebo-Controlled Clinical Trials

ERIC Educational Resources Information Center

Wilens, Timothy E.; Gault, Laura M.; Childress, Ann; Kratochvil, Christopher J.; Bensman, Lindsey; Hall, Coleen M.; Olson, Evelyn; Robieson, Weining Z.; Garimella, Tushar S.; Abi-Saab, Walid M.; Apostol, George; Saltarelli, Mario D.

2011-01-01

Objective: To assess the safety and efficacy of ABT-089, a novel alpha[subscript 4]beta[subscript 2] neuronal nicotinic receptor partial agonist, vs. placebo in children with attention-deficit/hyperactivity disorder (ADHD). Method: Two multicenter, randomized, double-blind, placebo-controlled, parallel-group studies of children 6 through 12 years…

Combining Randomized and Non-Randomized Evidence in Clinical Research: A Review of Methods and Applications

ERIC Educational Resources Information Center

Verde, Pablo E.; Ohmann, Christian

2015-01-01

Researchers may have multiple motivations for combining disparate pieces of evidence in a meta-analysis, such as generalizing experimental results or increasing the power to detect an effect that a single study is not able to detect. However, while in meta-analysis, the main question may be simple, the structure of evidence available to answer it…

A School-Randomized Clinical Trial of an Integrated Social-Emotional Learning and Literacy Intervention: Impacts after 1 School Year

ERIC Educational Resources Information Center

Jones, Stephanie M.; Brown, Joshua L.; Hoglund, Wendy L. G.; Aber, J. Lawrence

2010-01-01

Objective: To report experimental impacts of a universal, integrated school-based intervention in social-emotional learning and literacy development on change over 1 school year in 3rd-grade children's social-emotional, behavioral, and academic outcomes. Method: This study employed a school-randomized, experimental design and included 942…

ModerateDrinking.com and Moderation Management: Outcomes of a Randomized Clinical Trial with Non-Dependent Problem Drinkers

ERIC Educational Resources Information Center

Hester, Reid K.; Delaney, Harold D.; Campbell, William

2011-01-01

Objective: To evaluate the effectiveness of a web-based protocol, ModerateDrinking.com (MD; "www.moderatedrinking.com") combined with use of the online resources of Moderation Management (MM; "www.moderation.org") as opposed to the use of the online resources of MM alone. Method: We randomly assigned 80 problem drinkers to…

The Acute Effect of Methylphenidate in Brazilian Male Children and Adolescents with ADHD: A Randomized Clinical Trial

ERIC Educational Resources Information Center

Szobot, C. M.; Ketzer, C.; Parente, M. A.; Biederman, J.; Rohde, L. A.

2004-01-01

Objective: To evaluate the acute efficacy of methylphenidate (MPH) in Brazilian male children and adolescents with ADHD. Method: In a 4-day, double-blind, placebo-controlled, randomized, fix dose escalating, parallel-group trial, 36 ADHD children and adolescents were allocated to two groups: MPH (n = 19) and placebo (n = 17). Participants were…

Clinical comparison of two different plating methods in minimally invasive plate osteosynthesis for clavicular midshaft fractures: A randomized controlled trial.

PubMed

Sohn, Hoon-Sang; Shon, Min Soo; Lee, Kyung-Hag; Song, Si-Jung

2015-11-01

The aim of this study was to compare the clinical and radiographic outcomes between two different plating methods (superior vs. anteroinferior) in minimally invasive plate osteosynthesis (MIPO) for acute displaced clavicular shaft fractures. A prospective, randomized controlled trial was performed in a single centre. Nineteen patients were treated with superior plating and 18 with anteroinferior plating using the MIPO technique. A 3.5-mm locking reconstruction plate was bent preoperatively and applied to either the anteroinferior or superior aspect of the clavicle through two separate incisions. The operating time, time to union, the proportional length difference, complications, and functional outcome of the shoulder joint were evaluated using the Constant score and the University of California Los Angeles (UCLA) score. There was no statistically significant difference in the Constant score and UCLA score. The mean time to union was 16.8 weeks for superior plating and 17.1 weeks for anteroinferior plating (p=0.866). The average operation time was 77.2min in superior plating and 79.4min in anteroinferior plating (p=0.491). One patient in the superior plating group showed plate failure. Despite no significant difference, one patient had nonunion in the superior plating group (p>0.999). From a clinical perspective, although MIPO with anteroinferior plating provides better outcomes especially in complications without statistically significant difference, both plating methods provided satisfactory clinical and radiographic outcomes. Level I, a single-centre, prospective, randomized controlled trial. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of Four Pulpotomy Techniques in Primary Molars: A Randomized Controlled Trial

PubMed Central

Ansari, Ghassem; Morovati, Seyyedeh Pouya; Asgary, Saeed

2018-01-01

Introduction: This trial was designed to evaluate the clinical and radiographic success rates of calcium-enriched mixture (CEM) cement with and without low level laser therapy (LLLT) and compare them to that of formocresol (FC) and ferric sulfate (FS) in primary molar pulpotomies. Methods and Materials: This randomized clinical trial was conducted on a total of 160 teeth selected from 40 patients aged 3-9 years. Patients with at least four primary molars needing pulpotomy, were included in order to have each tooth assigned randomly in one of the four following groups; FC, FS, CEM, and LLLT/CEM. Six- and twelve-month follow-up periods were conducted in order to enable a clinical and radiographic evaluation of the treated teeth. Collected data were analyzed using Cochran Q Tests. Results: The 12-month clinical success rate for each technique was: FC=100%, FS=95%, CEM=97.5% and LLLT/CEM=100% with no significant differences (P>0.05). Furthermore, 12-month radiographic success rate for each technique was: FC=100%, FS=92.5%, CEM=95% and LLLT/CEM=100% with no significant differences (P>0.05). Conclusion: Favorable outcomes of four treatment techniques in pulpotomy of primary molar teeth were comparable. CEM with/without LLLT may be considered as a safe and successful pulpotomy treatment modality compared to current conventional methods. PMID:29692828

Do mobile family planning clinics facilitate vasectomy use in Nepal?

PubMed

Padmadas, Sabu S; Amoako Johnson, Fiifi; Leone, Tiziana; Dahal, Govinda P

2014-06-01

Nepal has a distinct topography that makes reproductive health and family planning services difficult to access, particularly in remote mountain and hill regions where over a quarter of modern contraceptive users rely exclusively on vasectomy. A three-level random intercept logistic regression analysis was applied on data from the 2011 Nepal Demographic and Health Survey to investigate the extent of influence of mobile family planning clinics on the odds of a male or a female sterilization, adjusting for relevant characteristics including ecological differences and random effects. The analyses included a sample of 2014 sterilization users, considering responses from currently married women of reproductive ages. The odds of a male sterilization were significantly higher in a mobile clinic than those in a government hospital (odds ratio, 1.65; 95% confidence interval, 1.21-2.25). The effects remained unaltered and statistically significant after adjusting for sociodemographic and clustering effects. Random effects were highly significant, which suggest the extent of heterogeneity in vasectomy use at the community and district levels. The odds of vasectomy use in mobile clinics were significantly higher among couples residing in hill and mountain regions and among those with three or more sons or those with only daughters. Mobile clinics significantly increase the uptake of vasectomy in hard-to-reach areas of Nepal. Reproductive health interventions should consider mobile clinics as an effective strategy to improve access to male-based modern methods and enhance gender equity in family planning. Family planning interventions in hard-to-reach communities could consider mobile clinic as an effective strategy to promote male-based modern methods. Improving access to vasectomy could substantially reduce unmet need for family planning in countries experiencing rapid fertility transition. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of Age Expectations on Oncology Social Workers' Clinical Judgment

ERIC Educational Resources Information Center

Conlon, Annemarie; Choi, Namkee G.

2014-01-01

Objective: This study examined the influence of oncology social workers' expectations regarding aging (ERA) and ERA with cancer (ERAC) on their clinical judgment. Methods: Oncology social workers (N = 322) were randomly assigned to one of four vignettes describing a patient with lung cancer. The vignettes were identical except for the patent's age…

Psychiatric Syndromes in Adolescents with Marijuana Abuse and Dependency in Outpatient Treatment

ERIC Educational Resources Information Center

Diamond, Guy; Panichelli-Mindel, Susan M.; Shera, David; Dennis, Mike; Tims, Frank; Ungemack, Jane

2006-01-01

Objective: The purpose of the current study to assist in understanding the prevalence and clinical correlates of psychiatric distress in adolescents seeking outpatient services for marijuana abuse or dependency. Methods: In a multi-site randomized clinical trial, 600 adolescents and their parents were assessed at intake using the Global Appraisals…

Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS): Demographic and Clinical Characteristics

ERIC Educational Resources Information Center

Frazier, Jean A.; McClellan, Jon; Findling, Robert L.; Vitiello, Benedetto; Anderson, Robert; Zablotsky, Benjamin; Williams, Emily; McNamara, Nora K.; Jackson, Joseph A.; Ritz, Louise; Hlastala, Stefanie A.; Pierson, Leslie; Varley, Jennifer A.; Puglia, Madeline; Maloney, Ann E.; Ambler, Denisse; Hunt-Harrison, Tyehimba; Hamer, Robert M.; Noyes, Nancy; Lieberman, Jeffrey A.; Sikich, Linmarie

2007-01-01

Objective: We examined baseline demographic and clinical profiles of youths enrolled from 2001 to 2006 in the publicly funded multicenter, randomized controlled trial Treatment of Early-Onset Schizophrenia Spectrum Disorders. Method: Youths (8-19 years) with schizophrenia (SZ) and schizoaffective disorder were recruited at four academic sites.…

Mental Health and Clinical Correlates in Lesbian, Gay, Bisexual, and Queer Young Adults

ERIC Educational Resources Information Center

Grant, Jon E.; Odlaug, Brian L.; Derbyshire, Katherine; Schreiber, Liana R. N.; Lust, Katherine; Christenson, Gary

2014-01-01

Objective: This study examined the prevalence of mental health disorders and their clinical correlates in a university sample of lesbian, gay, bisexual, and queer (LGBQ) students. Participants: College students at a large public university. Methods: An anonymous, voluntary survey was distributed via random e-mail generation to university students…

A unified procedure for meta-analytic evaluation of surrogate end points in randomized clinical trials

PubMed Central

Dai, James Y.; Hughes, James P.

2012-01-01

The meta-analytic approach to evaluating surrogate end points assesses the predictiveness of treatment effect on the surrogate toward treatment effect on the clinical end point based on multiple clinical trials. Definition and estimation of the correlation of treatment effects were developed in linear mixed models and later extended to binary or failure time outcomes on a case-by-case basis. In a general regression setting that covers nonnormal outcomes, we discuss in this paper several metrics that are useful in the meta-analytic evaluation of surrogacy. We propose a unified 3-step procedure to assess these metrics in settings with binary end points, time-to-event outcomes, or repeated measures. First, the joint distribution of estimated treatment effects is ascertained by an estimating equation approach; second, the restricted maximum likelihood method is used to estimate the means and the variance components of the random treatment effects; finally, confidence intervals are constructed by a parametric bootstrap procedure. The proposed method is evaluated by simulations and applications to 2 clinical trials. PMID:22394448

Investigating bang for your training buck: a randomized controlled trial comparing three methods of training clinicians in two core strategies of dialectical behavior therapy.

PubMed

Dimeff, Linda A; Harned, Melanie S; Woodcock, Eric A; Skutch, Julie M; Koerner, Kelly; Linehan, Marsha M

2015-05-01

The present study examined the efficacy of online training (OLT), instructor-led training (ILT), and a treatment manual (TM) in training mental health clinicians in two core strategies of Dialectical Behavior Therapy (DBT): chain analysis and validation. A randomized controlled trial compared OLT, ILT, and TM among clinicians naïve to DBT (N=172) who were assessed at baseline, post-training, and 30, 60, and 90 days following training. Primary outcomes included satisfaction, self-efficacy, motivation, knowledge, clinical proficiency, and clinical use. Overall, ILT outperformed OLT and TM in satisfaction, self-efficacy, and motivation, whereas OLT was the most effective method for increasing knowledge. The conditions did not differ in observer-rated clinical proficiency or self-reported clinical use, which both increased to moderate levels after training. In addition, ILT was particularly effective at improving motivation to use chain analysis, whereas OLT was particularly effective at increasing knowledge of validation strategies. These findings suggest that these types of brief, didactic trainings may be effective methods of increasing knowledge of new treatment strategies, but may not be sufficient to enable clinicians to achieve a high level of clinical use or proficiency. Additional research examining the possible advantages of matching training methods to types of treatment strategies may help to determine a tailored, more effective approach to training clinicians in empirically supported treatments. Copyright © 2015. Published by Elsevier Ltd.

Generalizing Evidence From Randomized Clinical Trials to Target Populations

PubMed Central

Cole, Stephen R.; Stuart, Elizabeth A.

2010-01-01

Properly planned and conducted randomized clinical trials remain susceptible to a lack of external validity. The authors illustrate a model-based method to standardize observed trial results to a specified target population using a seminal human immunodeficiency virus (HIV) treatment trial, and they provide Monte Carlo simulation evidence supporting the method. The example trial enrolled 1,156 HIV-infected adult men and women in the United States in 1996, randomly assigned 577 to a highly active antiretroviral therapy and 579 to a largely ineffective combination therapy, and followed participants for 52 weeks. The target population was US people infected with HIV in 2006, as estimated by the Centers for Disease Control and Prevention. Results from the trial apply, albeit muted by 12%, to the target population, under the assumption that the authors have measured and correctly modeled the determinants of selection that reflect heterogeneity in the treatment effect. In simulations with a heterogeneous treatment effect, a conventional intent-to-treat estimate was biased with poor confidence limit coverage, but the proposed estimate was largely unbiased with appropriate confidence limit coverage. The proposed method standardizes observed trial results to a specified target population and thereby provides information regarding the generalizability of trial results. PMID:20547574

A theory of eu-estrogenemia: a unifying concept

PubMed Central

Turner, Ralph J.; Kerber, Irwin J.

2017-01-01

Abstract Objective: The aim of the study was to propose a unifying theory for the role of estrogen in postmenopausal women through examples in basic science, randomized controlled trials, observational studies, and clinical practice. Methods: Review and evaluation of the literature relating to estrogen. Discussion: The role of hormone therapy and ubiquitous estrogen receptors after reproductive senescence gains insight from basic science models. Observational studies and individualized patient care in clinical practice may show outcomes that are not reproduced in randomized clinical trials. The understanding gained from the timing hypothesis for atherosclerosis, the critical window theory in neurosciences, randomized controlled trials, and numerous genomic and nongenomic actions of estrogen discovered in basic science provides new explanations to clinical challenges that practitioners face. Consequences of a hypo-estrogenemic duration in women's lives are poorly understood. The Study of Women Across the Nation suggests its magnitude is greater than was previously acknowledged. We propose that the healthy user bias was the result of surgical treatment (hysterectomy with oophorectomy) for many gynecological maladies followed by pharmacological and physiological doses of estrogen to optimize patient quality of life. The past decade of research has begun to demonstrate the role of estrogen in homeostasis. Conclusions: The theory of eu-estrogenemia provides a robust framework to unify the timing hypothesis, critical window theory, randomized controlled trials, the basic science of estrogen receptors, and clinical observations of patients over the past five decades. PMID:28562489

Understanding health economic analysis in critical care: insights from recent randomized controlled trials.

PubMed

Sud, Sachin; Cuthbertson, Brian H

2011-10-01

The article reviews the methods of health economic analysis (HEA) in clinical trials of critically ill patients. Emphasis is placed on the usefulness of HEA in the context of positive and 'no effect' studies, with recent examples. The need to control costs and promote effective spending in caring for the critically ill has garnered considerable attention due to the high cost of critical illness. Many clinical trials focus on short-term mortality, ignoring costs and quality of life, and fail to change clinical practice or promote efficient use of resources. Incorporating HEA into clinical trials is a possible solution. Such studies have shown some interventions, although expensive, provide good value, whereas others should be withdrawn from clinical practice. Incorporating HEA into randomized controlled trials (RCTs) requires careful attention to collect all relevant costs. Decision trees, modeling assumptions and methods for collecting costs and measuring outcomes should be planned and published beforehand to minimize bias. Costs and cost-effectiveness are potentially useful outcomes in RCTs of critically ill patients. Future RCTs should incorporate parallel HEA to provide both economic outcomes, which are important to the community, alongside patient-centered outcomes, which are important to individuals.

Clinical evaluation of a novel herbal dental cream in plaque formation: a double-blind, randomized, controlled clinical trial

PubMed Central

Amrutesh, Sunita; Malini, J; Tandur, Prakash S; Patki, Pralhad S

2010-01-01

Background The aim of this study was to evaluate the efficacy and safety of herbal dental cream in comparison to fluoride dental cream. Objectives Clinical evaluation of a novel herbal dental cream in plaque formation: a double-blind, randomized, controlled clinical trial. Methods One hundred and two patients with established dental plaque were randomly assigned to either herbal dental group or fluoride dental group for six weeks in a double-blind design. Improvement in plaque index, oral hygiene status, bleeding index, and gingival index was evaluated in these patients along with microbiological study. Results Results indicated a significant reduction in plaque index, gingival index, oral hygiene index, and microbial growth in both groups. Difference between the groups was not significant. There was no significant change in bleeding index. No adverse events were reported and both the dental creams were well tolerated. Conclusion The finding of this preliminary study indicates that herbal dental cream is as safe and effective as fluoride dental cream, but not superior to it. PMID:27186096

Improving metabolic parameters of antipsychotic child treatment (IMPACT) study: rationale, design, and methods

PubMed Central

2013-01-01

Background Youth with serious mental illness may experience improved psychiatric stability with second generation antipsychotic (SGA) medication treatment, but unfortunately may also experience unhealthy weight gain adverse events. Research on weight loss strategies for youth who require ongoing antipsychotic treatment is quite limited. The purpose of this paper is to present the design, methods, and rationale of the Improving Metabolic Parameters in Antipsychotic Child Treatment (IMPACT) study, a federally funded, randomized trial comparing two pharmacologic strategies against a control condition to manage SGA-related weight gain. Methods The design and methodology considerations of the IMPACT trial are described and embedded in a description of health risks associated with antipsychotic-related weight gain and the limitations of currently available research. Results The IMPACT study is a 4-site, six month, randomized, open-label, clinical trial of overweight/obese youth ages 8–19 years with pediatric schizophrenia-spectrum and bipolar-spectrum disorders, psychotic or non-psychotic major depressive disorder, or irritability associated with autistic disorder. Youth who have experienced clinically significant weight gain during antipsychotic treatment in the past 3 years are randomized to either (1) switch antipsychotic plus healthy lifestyle education (HLE); (2) add metformin plus HLE; or (3) HLE with no medication change. The primary aim is to compare weight change (body mass index z-scores) for each pharmacologic intervention with the control condition. Key secondary assessments include percentage body fat, insulin resistance, lipid profile, psychiatric symptom stability (monitored independently by the pharmacotherapist and a blinded evaluator), and all-cause and specific cause discontinuation. This study is ongoing, and the targeted sample size is 132 youth. Conclusion Antipsychotic-related weight gain is an important public health issue for youth requiring ongoing antipsychotic treatment to maintain psychiatric stability. The IMPACT study provides a model for pediatric research on adverse event management using state-of-the art methods. The results of this study will provide needed data on risks and benefits of two pharmacologic interventions that are already being used in pediatric clinical settings but that have not yet been compared directly in randomized trials. Trial registration Clinical Trials.gov NCT00806234 PMID:23947389

A novel complete-case analysis to determine statistical significance between treatments in an intention-to-treat population of randomized clinical trials involving missing data.

PubMed

Liu, Wei; Ding, Jinhui

2018-04-01

The application of the principle of the intention-to-treat (ITT) to the analysis of clinical trials is challenged in the presence of missing outcome data. The consequences of stopping an assigned treatment in a withdrawn subject are unknown. It is difficult to make a single assumption about missing mechanisms for all clinical trials because there are complicated reactions in the human body to drugs due to the presence of complex biological networks, leading to data missing randomly or non-randomly. Currently there is no statistical method that can tell whether a difference between two treatments in the ITT population of a randomized clinical trial with missing data is significant at a pre-specified level. Making no assumptions about the missing mechanisms, we propose a generalized complete-case (GCC) analysis based on the data of completers. An evaluation of the impact of missing data on the ITT analysis reveals that a statistically significant GCC result implies a significant treatment effect in the ITT population at a pre-specified significance level unless, relative to the comparator, the test drug is poisonous to the non-completers as documented in their medical records. Applications of the GCC analysis are illustrated using literature data, and its properties and limits are discussed.

A comparison between orthogonal and parallel plating methods for distal humerus fractures: a prospective randomized trial.

PubMed

Lee, Sang Ki; Kim, Kap Jung; Park, Kyung Hoon; Choy, Won Sik

2014-10-01

With the continuing improvements in implants for distal humerus fractures, it is expected that newer types of plates, which are anatomically precontoured, thinner and less irritating to soft tissue, would have comparable outcomes when used in a clinical study. The purpose of this study was to compare the clinical and radiographic outcomes in patients with distal humerus fractures who were treated with orthogonal and parallel plating methods using precontoured distal humerus plates. Sixty-seven patients with a mean age of 55.4 years (range 22-90 years) were included in this prospective study. The subjects were randomly assigned to receive 1 of 2 treatments: orthogonal or parallel plating. The following results were assessed: operating time, time to fracture union, presence of a step or gap at the articular margin, varus-valgus angulation, functional recovery, and complications. No intergroup differences were observed based on radiological and clinical results between the groups. In our practice, no significant differences were found between the orthogonal and parallel plating methods in terms of clinical outcomes, mean operation time, union time, or complication rates. There were no cases of fracture nonunion in either group; heterotrophic ossification was found 3 patients in orthogonal plating group and 2 patients in parallel plating group. In our practice, no significant differences were found between the orthogonal and parallel plating methods in terms of clinical outcomes or complication rates. However, orthogonal plating method may be preferred in cases of coronal shear fractures, where posterior to anterior fixation may provide additional stability to the intraarticular fractures. Additionally, parallel plating method may be the preferred technique used for fractures that occur at the most distal end of the humerus.

Comparing community and specialty provider-based recruitment in a randomized clinical trial: clinical trial in fecal incontinence.

PubMed

Whitebird, Robin R; Bliss, Donna Zimmaro; Savik, Kay; Lowry, Ann; Jung, Hans-Joachim G

2010-12-01

Recruitment of participants to clinical trials remains a significant challenge, especially for research addressing topics of a sensitive nature such as fecal incontinence (FI). In the Fiber Study, a randomized controlled trial on symptom management for FI, we successfully enrolled 189 community-living adults through collaborations with specialty-based and community-based settings, each employing methods tailored to the organizational characteristics of their site. Results show that using the two settings increased racial and ethnic diversity of the sample and inclusion of informal caregivers. There were no differential effects on enrollment, final eligibility, or completion of protocol by site. Strategic collaborations with complementary sites can achieve sample recruitment goals for clinical trials on topics that are sensitive or known to be underreported. Copyright © 2010 Wiley Periodicals, Inc.

A Pilot Study of Parent Mentors for Early Childhood Obesity.

PubMed

Foster, Byron A; Aquino, Christian A; Gil, Mario; Gelfond, Jonathan A L; Hale, Daniel E

2016-01-01

Objective. To assess the feasibility of a parent mentor model of intervention for early childhood obesity using positive deviance-based methods to inform the intervention. Methods. In this pilot, randomized clinical trial, parent-child dyads (age: 2-5) with children whose body mass index (BMI) was ≥95th percentile were randomized to parent mentor intervention or community health worker comparison. The child's height and weight were measured at baseline, after the six-month intervention, and six months after the intervention. Feasibility outcomes were recruitment, participation, and retention. The primary clinical outcome was BMI z-score change. Results. Sixty participants were enrolled, and forty-eight completed the six-month intervention. At baseline, the BMI z-score in the parent mentor group was 2.63 (SD = 0.65) and in the community health worker group it was 2.61 (SD = 0.89). For change in BMI z-score over time, there was no difference by randomization group at the end of the intervention: -0.02 (95% CI: -0.26, 0.22). At the end of the intervention, the BMI z-score for the parent mentor group was 2.48 (SD = 0.58) and for the community health worker group it was 2.45 (SD = 0.91), both reduced from baseline, p < 0.001. Conclusion. The model of a parent mentor clinical trial is feasible, and both randomized groups experienced small, sustained effects on adiposity in an obese, Hispanic population.

Maternal Opioid Treatment: Human Experimental Research (MOTHER) – Approach, Issues, and Lessons Learned

PubMed Central

Jones, Hendrée E.; Fischer, Gabriele; Heil, Sarah H.; Kaltenbach, Karol; Martin, Peter R.; Coyle, Mara G.; Selby, Peter; Stine, Susan M.; O’Grady, Kevin E.; Arria, Amelia M.

2015-01-01

Aims The Maternal Opioid Treatment: Human Experimental Research (MOTHER) project, an eight-site randomized, double-blind, double-dummy, flexible-dosing, parallel-group clinical trial is described. This study is the most current – and single most comprehensive – research effort to investigate the safety and efficacy of maternal and prenatal exposure to methadone and buprenorphine. Methods The MOTHER study design is outlined, and its basic features are presented. Conclusions At least seven important lessons have been learned from the MOTHER study: (1) an interdisciplinary focus improves the design and methods of a randomized clinical trial; (2) multiple sites in a clinical trial present continuing challenges to the investigative team due to variations in recruitment goals, patient populations, and hospital practices that in turn differentially impact recruitment rates, treatment compliance, and attrition; (3) study design and protocols must be flexible in order to meet the unforeseen demands of both research and clinical management; (4) staff turnover needs to be addressed with a proactive focus on both hiring and training; (5) the implementation of a protocol for the treatment of a particular disorder may identify important ancillary clinical issues worthy of investigation; (6) timely tracking of data in a multi-site trial is both demanding and unforgiving; and, (7) complex multi-site trials pose unanticipated challenges that complicate the choice of statistical methods, thereby placing added demands on investigators to effectively communicate their results. PMID:23106924

Concordance of Race or Ethnicity of Interventionists and Caregivers of Dementia Patients: Relationship to Attrition and Treatment Outcomes in the REACH Study

ERIC Educational Resources Information Center

McGinnis, Kathleen A.; Schulz, Richard; Stone, Roslyn A.; Klinger, Julie; Mercurio, Rocco

2006-01-01

Purpose: We assess the effects of racial or ethnic concordance between caregivers and interventionists on caregiver attrition, change in depression, and change in burden in a multisite randomized clinical trial. Design and Methods: Family caregivers of patients with Alzheimer's disease were randomized to intervention or control groups at six sites…

Early Effects of Responsivity Education/Prelinguistic Milieu Teaching for Children with Developmental Delays and Their Parents

ERIC Educational Resources Information Center

Fey, Marc E.; Warren, Steven F.; Brady, Nancy; Finestack, Lizbeth H.; Bredin-Oja, Shelley L.; Fairchild, Martha; Sokol, Shari; Yoder, Paul J.

2006-01-01

Purpose: To evaluate the efficacy of a 6-month course of responsivity education/prelinguistic milieu teaching (RE/PMT) for children with developmental delay and RE/PMT's effects on parenting stress in a randomized clinical trial. Method: Fifty-one children, age 24-33 months, with no more than 10 expressive words or signs, were randomly assigned to…

When They Call, Will They Come? A Contextually Responsive Approach for Engaging Multistressed Families in an Urban Child Mental Health Center: A Randomized Clinical Trial

ERIC Educational Resources Information Center

Stern, Susan B.; Walsh, Margaret; Mercado, Micaela; Levene, Kathryn; Pepler, Debra J.; Carr, Ashley; Heppell, Allison; Lowe, Erin

2015-01-01

Objective: This study examines the effect of an ecological and contextually responsive approach, during initial intake call, on engagement for multistressed families seeking child mental health services in an urban setting. Methods: Using a randomized design, parents were allocated to phone Intake As Usual (IAU) or Enhanced Engagement Phone Intake…

A randomized controlled trial of acupuncture and moxibustion to treat Bell's palsy according to different stages: design and protocol.

PubMed

Chen, Xiaoqin; Li, Ying; Zheng, Hui; Hu, Kaming; Zhang, Hongxing; Zhao, Ling; Li, Yan; Liu, Lian; Mang, Lingling; Yu, Shuyuan

2009-07-01

Acupuncture to treat Bell's palsy is one of the most commonly used methods in China. There are a variety of acupuncture treatment options to treat Bell's palsy in clinical practice. Since Bell's palsy has three different path-stages (acute stage, resting stage and restoration stage), so whether acupuncture is effective in the different path-stages and which acupuncture treatment is the best method are major issues in acupuncture clinical trials about Bell's palsy. In this article, we report the design and protocol of a large sample multi-center randomized controlled trial to treat Bell's palsy with acupuncture. There are five acupuncture groups, with four according to different path-stages and one not. In total, 900 patients with Bell's palsy are enrolled in this study. These patients are randomly assigned to receive one of the following four treatment groups according to different path-stages, i.e. 1) staging acupuncture group, 2) staging acupuncture and moxibustion group, 3) staging electro-acupuncture group, 4) staging acupuncture along yangming musculature group or non-staging acupuncture control group. The outcome measurements in this trial are the effect comparison achieved among these five groups in terms of House-Brackmann scale (Global Score and Regional Score), Facial Disability Index scale, Classification scale of Facial Paralysis, and WHOQOL-BREF scale before randomization (baseline phase) and after randomization. The result of this trial will certify the efficacy of using staging acupuncture and moxibustion to treat Bell's palsy, and to approach a best acupuncture treatment among these five different methods for treating Bell's palsy.

Feasibility of a Clinical Trial of Vision Therapy for Treatment of Amblyopia

PubMed Central

Lyon, Don W.; Hopkins, Kristine; Chu, Raymond H.; Tamkins, Susanna M.; Cotter, Susan A.; Melia, B. Michele; Holmes, Jonathan M.; Repka, Michael X.; Wheeler, David T.; Sala, Nicholas A.; Dumas, Janette; Silbert, David I.

2013-01-01

Purpose We conducted a pilot randomized clinical trial of office-based active vision therapy for the treatment of childhood amblyopia to determine the feasibility of conducting a full-scale randomized clinical trial. Methods A training and certification program and manual of procedures were developed to certify therapists to administer a standardized vision therapy program in ophthalmology and optometry offices consisting of weekly visits for 16 weeks. Nineteen children, 7 to less than 13 years of age, with amblyopia (20/40–20/100) were randomly assigned to receive either 2 hours of daily patching with active vision therapy or 2 hours of daily patching with placebo vision therapy. Results Therapists in diverse practice settings were successfully trained and certified to perform standardized vision therapy in strict adherence with protocol. Subjects completed 85% of required weekly in-office vision therapy visits. Eligibility criteria based on age, visual acuity, and stereoacuity, designed to identify children able to complete a standardized vision therapy program and judged likely to benefit from this treatment, led to a high proportion of screened subjects being judged ineligible, resulting in insufficient recruitment. There were difficulties in retrieving adherence data for the computerized home therapy procedures. Conclusions This study demonstrated that a 16-week treatment trial of vision therapy was feasible with respect to maintaining protocol adherence; however, recruitment under the proposed eligibility criteria, necessitated by the standardized approach to vision therapy, was not successful. A randomized clinical trial of in-office vision therapy for the treatment of amblyopia would require broadening of the eligibility criteria and improved methods to gather objective data regarding the home therapy. A more flexible approach that customizes vision therapy based on subject age, visual acuity, and stereopsis, might be required to allow enrollment of a broader group of subjects. PMID:23563444

On the design and analysis of clinical trials with correlated outcomes

PubMed Central

Follmann, Dean; Proschan, Michael

2014-01-01

SUMMARY The convention in clinical trials is to regard outcomes as independently distributed, but in some situations they may be correlated. For example, in infectious diseases, correlation may be induced if participants have contact with a common infectious source, or share hygienic tips that prevent infection. This paper discusses the design and analysis of randomized clinical trials that allow arbitrary correlation among all randomized volunteers. This perspective generalizes the traditional perspective of strata, where patients are exchangeable within strata, and independent across strata. For theoretical work, we focus on the test of no treatment effect μ1 − μ0 = 0 when the n dimensional vector of outcomes follows a Gaussian distribution with known n × n covariance matrix Σ, where the half randomized to treatment (placebo) have mean response μ1 (μ0). We show how the new test corresponds to familiar tests in simple situations for independent, exchangeable, paired, and clustered data. We also discuss the design of trials where Σ is known before or during randomization of patients and evaluate randomization schemes based on such knowledge. We provide two complex examples to illustrate the method, one for a study of 23 family clusters with cardiomyopathy, the other where the malaria attack rates vary within households and clusters of households in a Malian village. PMID:25111420

High Mortality without ESCAPE: The Registry of Heart Failure Patients Receiving Pulmonary Artery Catheters without Randomization

PubMed Central

Allen, Larry A.; Rogers, Joseph G.; Warnica, J. Wayne; DiSalvo, Thomas G.; Tasissa, Gudaye; Binanay, Cynthia; O’Connor, Christopher M.; Califf, Robert M.; Leier, Carl V.; Shah, Monica R.; Stevenson, Lynne W.

2008-01-01

Background In ESCAPE, there was no difference in days alive and out of the hospital for patients with decompensated heart failure (HF) randomly assigned to therapy guided by pulmonary artery catheter (PAC) plus clinical assessment versus clinical assessment alone. The external validity of these findings is debated. Methods and Results ESCAPE sites enrolled 439 patients receiving PAC without randomization in a prospective registry. Baseline characteristics, pertinent trial exclusion criteria, reasons for PAC use, hemodynamics, and complications were collected. Survival was determined from the National Death Index and the Alberta Registry. On average, registry patients had lower blood pressure, worse renal function, less neurohormonal antagonist therapy, and higher use of intravenous inotropes as compared with trial patients. Although clinical assessment anticipated less volume overload and greater hypoperfusion among the registry population, measured filling pressures were similarly elevated in the registry and trial, while measured perfusion was slightly higher among registry patients. Registry patients had longer hospitalization (13 vs. 6 days, p <0.001) and higher 6-month mortality (34% vs. 20%, p < 0.001) than trial patients. Conclusions The decision to use PAC without randomization identified a population with higher disease severity and risk of mortality. This prospective registry highlights the complex context of patient selection for randomized trials. PMID:18926438

Effectiveness of cross polarized light and fluorescence diagnosis for detection of sub-clinical and clinical actinic keratosis during imiquimod treatment.

PubMed

Ortonne, Jean-Paul; Gupta, Girish; Ortonne, Nicolas; Duteil, Luc; Queille, Catherine; Mallefet, Pascal

2010-07-01

During treatment of actinic keratosis (AK) lesions with imiquimod sub-clinical lesions often become visible. It is, however, unclear whether these sub-clinical lesions would be detectable beforehand. The aim of this pilot study was to compare two techniques, cross polarized light photography (CPL) and fluorescence diagnosis (FD) using methyllevulinic acid and illumination with Wood's lamp for their ability to detect sub-clinical lesions. These findings were also compared with biopsy results taken before and after treatment with imiquimod 5% cream or vehicle. Twelve patients with at least five clinically visible AK lesions in a single contiguous 20 cm(2) area on the head were recruited. Patient eligibility was determined at the screening visit, when they were randomized to treatment. The randomization was 3:1, active to vehicle (nine treated with imiquimod, three with vehicle cream) for a total duration of 24 weeks (six clinic visits). Patients were assessed for baseline AK lesion counts (clinical and sub-clinical) at the screening visit and final counts at week 20. The number of clinically observed AK lesions was significantly lower at week 12 and week 20 compared with baseline following imiquimod treatment versus vehicle. The number of counted lesions were significantly higher using the CPL method compared with clinical counting with imiquimod treatment at baseline (8.3 +/- 3.4 vs 5.8 +/- 1.3; P = 0.027) and week 20 (4.8 +/- 2.4 vs 3.0 +/- 1.7; P = 0.02) but not in the vehicle group. The FD lesion counting method did not show a significant increase in the number of detected lesions compared with clinical analysis in the imiquimod and placebo groups but when comparisons were performed using pooled data (treatments and visits combined) the results were significant. The number of sub-clinical and clinical AK lesions detected during treatment with imiquimod can be better demonstrated using the methods of CPL and FD, but statistical significance was reached only using the CPL method. This is only a preliminary study with a small number of patients and as a result it is difficult to conclude both statistical and clinical significance. However, results were encouraging and indicate that larger studies are needed to demonstrate the relevance of these two new methods for improved detection of clinical and especially sub-clinical AK lesions.

Sequential causal inference: Application to randomized trials of adaptive treatment strategies

PubMed Central

Dawson, Ree; Lavori, Philip W.

2009-01-01

SUMMARY Clinical trials that randomize subjects to decision algorithms, which adapt treatments over time according to individual response, have gained considerable interest as investigators seek designs that directly inform clinical decision making. We consider designs in which subjects are randomized sequentially at decision points, among adaptive treatment options under evaluation. We present a sequential method to estimate the comparative effects of the randomized adaptive treatments, which are formalized as adaptive treatment strategies. Our causal estimators are derived using Bayesian predictive inference. We use analytical and empirical calculations to compare the predictive estimators to (i) the ‘standard’ approach that allocates the sequentially obtained data to separate strategy-specific groups as would arise from randomizing subjects at baseline; (ii) the semi-parametric approach of marginal mean models that, under appropriate experimental conditions, provides the same sequential estimator of causal differences as the proposed approach. Simulation studies demonstrate that sequential causal inference offers substantial efficiency gains over the standard approach to comparing treatments, because the predictive estimators can take advantage of the monotone structure of shared data among adaptive strategies. We further demonstrate that the semi-parametric asymptotic variances, which are marginal ‘one-step’ estimators, may exhibit significant bias, in contrast to the predictive variances. We show that the conditions under which the sequential method is attractive relative to the other two approaches are those most likely to occur in real studies. PMID:17914714

What's in a title? An assessment of whether randomized controlled trial in a title means that it is one.

PubMed

Koletsi, Despina; Pandis, Nikolaos; Polychronopoulou, Argy; Eliades, Theodore

2012-06-01

In this study, we aimed to investigate whether studies published in orthodontic journals and titled as randomized clinical trials are truly randomized clinical trials. A second objective was to explore the association of journal type and other publication characteristics on correct classification. American Journal of Orthodontics and Dentofacial Orthopedics, European Journal of Orthodontics, Angle Orthodontist, Journal of Orthodontics, Orthodontics and Craniofacial Research, World Journal of Orthodontics, Australian Orthodontic Journal, and Journal of Orofacial Orthopedics were hand searched for clinical trials labeled in the title as randomized from 1979 to July 2011. The data were analyzed by using descriptive statistics, and univariable and multivariable examinations of statistical associations via ordinal logistic regression modeling (proportional odds model). One hundred twelve trials were identified. Of the included trials, 33 (29.5%) were randomized clinical trials, 52 (46.4%) had an unclear status, and 27 (24.1%) were not randomized clinical trials. In the multivariable analysis among the included journal types, year of publication, number of authors, multicenter trial, and involvement of statistician were significant predictors of correctly classifying a study as a randomized clinical trial vs unclear and not a randomized clinical trial. From 112 clinical trials in the orthodontic literature labeled as randomized clinical trials, only 29.5% were identified as randomized clinical trials based on clear descriptions of appropriate random number generation and allocation concealment. The type of journal, involvement of a statistician, multicenter trials, greater numbers of authors, and publication year were associated with correct clinical trial classification. This study indicates the need of clear and accurate reporting of clinical trials and the need for educating investigators on randomized clinical trial methodology. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

The Microbial Detection Array Combined with Random Phi29-Amplification Used as a Diagnostic Tool for Virus Detection in Clinical Samples

PubMed Central

Erlandsson, Lena; Rosenstierne, Maiken W.; McLoughlin, Kevin; Jaing, Crystal; Fomsgaard, Anders

2011-01-01

A common technique used for sensitive and specific diagnostic virus detection in clinical samples is PCR that can identify one or several viruses in one assay. However, a diagnostic microarray containing probes for all human pathogens could replace hundreds of individual PCR-reactions and remove the need for a clear clinical hypothesis regarding a suspected pathogen. We have established such a diagnostic platform for random amplification and subsequent microarray identification of viral pathogens in clinical samples. We show that Phi29 polymerase-amplification of a diverse set of clinical samples generates enough viral material for successful identification by the Microbial Detection Array, demonstrating the potential of the microarray technique for broad-spectrum pathogen detection. We conclude that this method detects both DNA and RNA virus, present in the same sample, as well as differentiates between different virus subtypes. We propose this assay for diagnostic analysis of viruses in clinical samples. PMID:21853040

Depression Care for Low-Income, Minority, Safety Net Clinic Populations with Comorbid Illness

ERIC Educational Resources Information Center

Ell, Kathleen; Lee, Pey-Jiuan; Xie, Bin

2010-01-01

Objective: Increasingly, mental health care is provided within the general health care sector. Accompanying this significant change is the demand for evidence-based as well as cost-effective or cost-neutral care models. Method: The authors present a pooled analysis of three large randomized clinical trials in which social workers provide…

Depression Screening Patterns for Women in Rural Health Clinics

ERIC Educational Resources Information Center

Tudiver, Fred; Edwards, Joellen Beckett; Pfortmiller, Deborah T.

2010-01-01

Context: Rates and types of screening for depression in rural primary care practices are unknown. Purpose: To identify rates of depression screening among rural women in a sample of rural health clinics (RHCs). Methods: A chart review of 759 women's charts in 19 randomly selected RHCs across the nation. Data were collected from charts of female…

A Pocock Approach to Sequential Meta-Analysis of Clinical Trials

ERIC Educational Resources Information Center

Shuster, Jonathan J.; Neu, Josef

2013-01-01

Three recent papers have provided sequential methods for meta-analysis of two-treatment randomized clinical trials. This paper provides an alternate approach that has three desirable features. First, when carried out prospectively (i.e., we only have the results up to the time of our current analysis), we do not require knowledge of the…

Recruitment strategies in two Reproductive Medicine Network infertility trials

PubMed Central

Usadi, Rebecca S.; Diamond, Michael P.; Legro, Richard S.; Schlaff, William D.; Hansen, Karl R.; Casson, Peter; Christman, Gregory; Bates, G. Wright; Baker, Valerie; Seungdamrong, Aimee; Rosen, Mitchell P.; Lucidi, Scott; Thomas, Tracey; Huang, Hao; Santoro, Nanette; Eisenberg, Esther; Zhang, Heping; Alvero, Ruben

2016-01-01

Background Recruitment of individuals into clinical trials is a critical step in completing studies. Reports examining the effectiveness of different recruitment strategies, and specifically in infertile couples, are limited. Methods We investigated recruitment methods used in two NIH sponsored trials, Pregnancy in Polycystic Ovary Syndrome (PPCOS II) and Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS), and examined which strategies yielded the greatest number of participants completing the trials. Results 3683 couples were eligible for screening. 1650 participants were randomized and 1339 completed the trials. 750 women were randomized in PPCOS II; 212 of the participants who completed the trial were referred by physicians. Participants recruited from radio ads (84/750) and the internet (81/750) resulted in similar rates of trial completion in PPCOS II. 900 participants were randomized in AMIGOS. 440 participants who completed the trial were referred to the study by physicians. The next most successful method in AMIGOS was use of the internet, achieving 78 completed participants. Radio ads proved the most successful strategy in both trials for participants who earned <$50,000 annually. Radio ads were most successful in enrolling white patients in PPCOS II and black patients in AMIGOS. Seven ancillary Clinical Research Scientist Training (CREST) sites enrolled 324 of the participants who completed the trials. Conclusions Physician referral was the most successful recruitment strategy. Radio ads and the internet were the next most successful strategies, particularly for women of limited income. Ancillary clinical sites were important for overall recruitment. PMID:26386293

A quantitative and qualitative evaluation of reports of clinical trials published in six Brazilian dental journals indexed in the Scientific Electronic Library Online (SciELO).

PubMed

de Souza, Raphael Freitas; Chaves, Carolina de Andrade Lima; Nasser, Mona; Fedorowicz, Zbys

2010-01-01

Open access publishing is becoming increasingly popular within the biomedical sciences. SciELO, the Scientific Electronic Library Online, is a digital library covering a selected collection of Brazilian scientific journals many of which provide open access to full-text articles.This library includes a number of dental journals some of which may include reports of clinical trials in English, Portuguese and/or Spanish. Thus, SciELO could play an important role as a source of evidence for dental healthcare interventions especially if it yields a sizeable number of high quality reports. The aim of this study was to identify reports of clinical trials by handsearching of dental journals that are accessible through SciELO, and to assess the overall quality of these reports. Electronic versions of six Brazilian dental Journals indexed in SciELO were handsearched at www.scielo.br in September 2008. Reports of clinical trials were identified and classified as controlled clinical trials (CCTs - prospective, experimental studies comparing 2 or more healthcare interventions in human beings) or randomized controlled trials (RCTs - a random allocation method is clearly reported), according to Cochrane eligibility criteria. CRITERIA TO ASSESS METHODOLOGICAL QUALITY INCLUDED: method of randomization, concealment of treatment allocation, blinded outcome assessment, handling of withdrawals and losses and whether an intention-to-treat analysis had been carried out. The search retrieved 33 CCTs and 43 RCTs. A majority of the reports provided no description of either the method of randomization (75.3%) or concealment of the allocation sequence (84.2%). Participants and outcome assessors were reported as blinded in only 31.2% of the reports. Withdrawals and losses were only clearly described in 6.5% of the reports and none mentioned an intention-to-treat analysis or any similar procedure. The results of this study indicate that a substantial number of reports of trials and systematic reviews are available in the dental journals listed in SciELO, and that these could provide valuable evidence for clinical decision making. However, it is clear that the quality of a number of these reports is of some concern and that improvement in the conduct and reporting of these trials could be achieved if authors adhered to internationally accepted guidelines, e.g. the CONSORT statement.

A Hybrid Process Fidelity Assessment in a Home-based Randomized Clinical Trial

PubMed Central

WILDE, MARY H.; LIEBEL, DIANNE; FAIRBANKS, EILEEN; WILSON, PAULA; LASH, MARGARET; SHAH, SHIVANI; McDONALD, MARGARET V.; BRASCH, JUDITH; ZHANG, FENG; SCHEID, EILEEN; McMAHON, JAMES M.

2016-01-01

A process fidelity assessment was conducted as a nested study within a home-based randomized clinical trial teaching self-management to 101 long-term indwelling urinary catheter users in the treatment group. Our hybrid model combined external assessments (outside observations and tape recordings) with internal evaluation methods (through study nurse forms and notes) for a comprehensive process fidelity assessment. Barriers, patient-related issues, and nurse perspectives were identified demonstrating the complexity in home care intervention research. The complementary and synergistic approaches provided in depth information about the context of the delivery and the impact of the intervention on study outcomes. PMID:25894688

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

Mortality risk prediction in burn injury: Comparison of logistic regression with machine learning approaches.

PubMed

Stylianou, Neophytos; Akbarov, Artur; Kontopantelis, Evangelos; Buchan, Iain; Dunn, Ken W

2015-08-01

Predicting mortality from burn injury has traditionally employed logistic regression models. Alternative machine learning methods have been introduced in some areas of clinical prediction as the necessary software and computational facilities have become accessible. Here we compare logistic regression and machine learning predictions of mortality from burn. An established logistic mortality model was compared to machine learning methods (artificial neural network, support vector machine, random forests and naïve Bayes) using a population-based (England & Wales) case-cohort registry. Predictive evaluation used: area under the receiver operating characteristic curve; sensitivity; specificity; positive predictive value and Youden's index. All methods had comparable discriminatory abilities, similar sensitivities, specificities and positive predictive values. Although some machine learning methods performed marginally better than logistic regression the differences were seldom statistically significant and clinically insubstantial. Random forests were marginally better for high positive predictive value and reasonable sensitivity. Neural networks yielded slightly better prediction overall. Logistic regression gives an optimal mix of performance and interpretability. The established logistic regression model of burn mortality performs well against more complex alternatives. Clinical prediction with a small set of strong, stable, independent predictors is unlikely to gain much from machine learning outside specialist research contexts. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

Comparing multiple competing interventions in the absence of randomized trials using clinical risk-benefit analysis

PubMed Central

2012-01-01

Background To demonstrate the use of risk-benefit analysis for comparing multiple competing interventions in the absence of randomized trials, we applied this approach to the evaluation of five anticoagulants to prevent thrombosis in patients undergoing orthopedic surgery. Methods Using a cost-effectiveness approach from a clinical perspective (i.e. risk benefit analysis) we compared thromboprophylaxis with warfarin, low molecular weight heparin, unfractionated heparin, fondaparinux or ximelagatran in patients undergoing major orthopedic surgery, with sub-analyses according to surgery type. Proportions and variances of events defining risk (major bleeding) and benefit (thrombosis averted) were obtained through a meta-analysis and used to define beta distributions. Monte Carlo simulations were conducted and used to calculate incremental risks, benefits, and risk-benefit ratios. Finally, net clinical benefit was calculated for all replications across a range of risk-benefit acceptability thresholds, with a reference range obtained by estimating the case fatality rate - ratio of thrombosis to bleeding. Results The analysis showed that compared to placebo ximelagatran was superior to other options but final results were influenced by type of surgery, since ximelagatran was superior in total knee replacement but not in total hip replacement. Conclusions Using simulation and economic techniques we demonstrate a method that allows comparing multiple competing interventions in the absence of randomized trials with multiple arms by determining the option with the best risk-benefit profile. It can be helpful in clinical decision making since it incorporates risk, benefit, and personal risk acceptance. PMID:22233221

Recruiting participants with peripheral arterial disease for clinical trials: experience from the Study to Improve Leg Circulation (SILC).

PubMed

McDermott, Mary M; Domanchuk, Kathryn; Dyer, Alan; Ades, Philip; Kibbe, Melina; Criqui, Michael H

2009-03-01

To describe the success of diverse recruitment methods in a randomized controlled clinical trial of exercise in persons with peripheral arterial disease (PAD). An analysis of recruitment sources conducted for the 746 men and women completing a baseline visit for the study to improve leg circulation (SILC), a randomized controlled trial of exercise for patients with PAD. For each recruitment source, we determined the number of randomized participants, the rate of randomization among those completing a baseline visit, and cost per randomized participant. Of the 746 individuals who completed a baseline visit, 156 were eligible and randomized. The most frequent sources of randomized participants were newspaper advertising (n = 67), mailed recruitment letters to patients with PAD identified at the study medical center (n = 25), and radio advertising (n = 18). Costs per randomized participant were $2750 for television advertising, $2167 for Life Line Screening, $2369 for newspaper advertising, $3931 for mailed postcards to older community dwelling men and women, and $5691 for radio advertising. Among those completing a baseline visit, randomization rates ranged from 10% for those identified from radio advertising to 32% for those identified from the Chicago Veterans Administration and 33% for those identified from posted flyers. Most participants in a randomized controlled trial of exercise were recruited from newspaper advertising and mailed recruitment letters to patients with known PAD. The highest randomization rates after a baseline visit occurred among participants identified from posted flyers and mailed recruitment letters to PAD patients.

Mechanical and Pharmacologic Methods of Labor Induction: A Randomized Controlled Trial

PubMed Central

Levine, Lisa D.; Downes, Katheryne L.; Elovitz, Michal A.; Parry, Samuel; Sammel, Mary D.; Srinivas, Sindhu K

2016-01-01

Objective To evaluate the effectiveness of four commonly used induction methods. Methods This randomized trial compared four induction methods: Misoprostol alone, Foley alone, Misoprostol–cervical Foley concurrently, and Foley–oxytocin concurrently,. Women undergoing labor induction with full term (≥37 weeks), singleton, vertex presenting gestations, with no contraindication to vaginal delivery, intact membranes, Bishop score ≤6, and cervical dilation ≤2cm were included. Women were enrolled only once during the study period. Our primary outcome was time to delivery. Neither patients nor providers were blinded to assigned treatment group since examinations are required for placement of all methods; however, research personnel were blinded during data abstraction. A sample size of 123 per group (N=492) was planned to compare the four groups pairwise (P≤.008), with a 4-hour reduction in delivery time considered clinically meaningful. Results From May 2013 through June 2015, 997 women were screened and 491 were randomized and analyzed. Demographic and clinical characteristics were similar among the four treatment groups. When comparing all induction method groups, combination methods achieved a faster median time to delivery than single-agent methods, (misoprostol–Foley: 13.1 hours, Foley–oxytocin: 14.5 hours, misoprostol: 17.6 hours, Foley: 17.7 hours, p<0.001). When censored for cesarean and adjusting for parity, women who received misoprostol–Foley delivered almost twice as likely to deliver before women who received misoprostol alone (hazard ratio (HR, 95% CI) 1.92 [1.42–2.59]) or Foley alone (HR, 95%CI: 1.87 [1.39–2.52]), whereas Foley–oxytocin was not statistically different from single-agent methods. Conclusion After censoring for cesarean and adjusting for parity, misoprostol–cervical Foley resulted in twice the chance of delivering before either single-agent method. PMID:27824758

Randomized clinical trials in dentistry: Risks of bias, risks of random errors, reporting quality, and methodologic quality over the years 1955-2013.

PubMed

Saltaji, Humam; Armijo-Olivo, Susan; Cummings, Greta G; Amin, Maryam; Flores-Mir, Carlos

2017-01-01

To examine the risks of bias, risks of random errors, reporting quality, and methodological quality of randomized clinical trials of oral health interventions and the development of these aspects over time. We included 540 randomized clinical trials from 64 selected systematic reviews. We extracted, in duplicate, details from each of the selected randomized clinical trials with respect to publication and trial characteristics, reporting and methodologic characteristics, and Cochrane risk of bias domains. We analyzed data using logistic regression and Chi-square statistics. Sequence generation was assessed to be inadequate (at unclear or high risk of bias) in 68% (n = 367) of the trials, while allocation concealment was inadequate in the majority of trials (n = 464; 85.9%). Blinding of participants and blinding of the outcome assessment were judged to be inadequate in 28.5% (n = 154) and 40.5% (n = 219) of the trials, respectively. A sample size calculation before the initiation of the study was not performed/reported in 79.1% (n = 427) of the trials, while the sample size was assessed as adequate in only 17.6% (n = 95) of the trials. Two thirds of the trials were not described as double blinded (n = 358; 66.3%), while the method of blinding was appropriate in 53% (n = 286) of the trials. We identified a significant decrease over time (1955-2013) in the proportion of trials assessed as having inadequately addressed methodological quality items (P < 0.05) in 30 out of the 40 quality criteria, or as being inadequate (at high or unclear risk of bias) in five domains of the Cochrane risk of bias tool: sequence generation, allocation concealment, incomplete outcome data, other sources of bias, and overall risk of bias. The risks of bias, risks of random errors, reporting quality, and methodological quality of randomized clinical trials of oral health interventions have improved over time; however, further efforts that contribute to the development of more stringent methodology and detailed reporting of trials are still needed.

Osteoporosis therapies: evidence from health-care databases and observational population studies.

PubMed

Silverman, Stuart L

2010-11-01

Osteoporosis is a well-recognized disease with severe consequences if left untreated. Randomized controlled trials are the most rigorous method for determining the efficacy and safety of therapies. Nevertheless, randomized controlled trials underrepresent the real-world patient population and are costly in both time and money. Modern technology has enabled researchers to use information gathered from large health-care or medical-claims databases to assess the practical utilization of available therapies in appropriate patients. Observational database studies lack randomization but, if carefully designed and successfully completed, can provide valuable information that complements results obtained from randomized controlled trials and extends our knowledge to real-world clinical patients. Randomized controlled trials comparing fracture outcomes among osteoporosis therapies are difficult to perform. In this regard, large observational database studies could be useful in identifying clinically important differences among therapeutic options. Database studies can also provide important information with regard to osteoporosis prevalence, health economics, and compliance and persistence with treatment. This article describes the strengths and limitations of both randomized controlled trials and observational database studies, discusses considerations for observational study design, and reviews a wealth of information generated by database studies in the field of osteoporosis.

Assessing the Eventual Publication of Clinical Trial Abstracts Submitted to a Large Annual Oncology Meeting

PubMed Central

Wang, Ruibin; Prasad, Vinay; Bates, Susan E.; Fojo, Tito

2016-01-01

Background. Despite the ethical imperative to publish clinical trials when human subjects are involved, such data frequently remain unpublished. The objectives were to tabulate the rate and ascertain factors associated with eventual publication of clinical trial results reported as abstracts in the Proceedings of the American Society of Clinical Oncology (American Society of Clinical Oncology). Materials and Methods. Abstracts describing clinical trials for patients with breast, lung, colorectal, ovarian, and prostate cancer from 2009 to 2011 were identified by using a comprehensive online database (http://meetinglibrary.asco.org/abstracts). Abstracts included reported results of a treatment or intervention assessed in a discrete, prospective clinical trial. Publication status at 4−6 years was determined by using a standardized search of PubMed. Primary outcomes were the rate of publication for abstracts of randomized and nonrandomized clinical trials. Secondary outcomes included factors influencing the publication of results. Results. A total of 1,075 abstracts describing 378 randomized and 697 nonrandomized clinical trials were evaluated. Across all years, 75% of randomized and 54% of nonrandomized trials were published, with an overall publication rate of 61%. Sample size was a statistically significant predictor of publication for both randomized and nonrandomized trials (odds ratio [OR] per increase of 100 participants = 1.23 [1.11–1.36], p < .001; and 1.64 [1.15–2.34], p = .006, respectively). Among randomized studies, an industry coauthor or involvement of a cooperative group increased the likelihood of publication (OR 2.37, p = .013; and 2.21, p = .01, respectively). Among nonrandomized studies, phase II trials were more likely to be published than phase I (p < .001). Use of an experimental agent was not a predictor of publication in randomized (OR 0.76 [0.38–1.52]; p = .441) or nonrandomized trials (OR 0.89 [0.61–1.29]; p = .532). Conclusion. This is the largest reported study examining why oncology trials are not published. The data show that 4−6 years after appearing as abstracts, 39% of oncology clinical trials remain unpublished. Larger sample size and advanced trial phase were associated with eventual publication; among randomized trials, an industry-affiliated author or a cooperative group increased likelihood of publication. Unfortunately, we found that, despite widespread recognition of the problem and the creation of central data repositories, timely publishing of oncology clinical trials results remains unsatisfactory. Implications for Practice: The Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects notes the ethical obligation to report clinical trial data, whether positive or negative. This obligation is listed alongside requirements for risk minimization, access, confidentiality, and informed consent, all bedrocks of the clinical trial system, yet clinical trials are often not published, particularly if negative or difficult to complete. This study found that among American Society for Clinical Oncology (ASCO) Annual Meeting abstracts, 2009–2011, only 61% were published 4–6 years later: 75% of randomized trials and 54% of nonrandomized trials. Clinicians need to insist that every study in which they participate is published. PMID:26888691

Methodological Issues in Trials of Complementary and Alternative Medicine Interventions

PubMed Central

Sikorskii, Alla; Wyatt, Gwen; Victorson, David; Faulkner, Gwen; Rahbar, Mohammad Hossein

2010-01-01

Background Complementary and alternative medicine (CAM) use is widespread among cancer patients. Information on safety and efficacy of CAM therapies is needed for both patients and health care providers. Well-designed randomized clinical trials (RCTs) of CAM therapy interventions can inform both clinical research and practice. Objectives To review important issues that affect the design of RCTs for CAM interventions. Methods Using the methods component of the Consolidated Standards for Reporting Trials (CONSORT) as a guiding framework, and a National Cancer Institute-funded reflexology study as an exemplar, methodological issues related to participants, intervention, objectives, outcomes, sample size, randomization, blinding, and statistical methods were reviewed. Discussion Trials of CAM interventions designed and implemented according to appropriate methodological standards will facilitate the needed scientific rigor in CAM research. Interventions in CAM can be tested using proposed methodology, and the results of testing will inform nursing practice in providing safe and effective supportive care and improving the well-being of patients. PMID:19918155

Clinic Versus Online Social Network–Delivered Lifestyle Interventions: Protocol for the Get Social Noninferiority Randomized Controlled Trial

PubMed Central

Wang, Monica L; Waring, Molly E; Jake-Schoffman, Danielle E; Oleski, Jessica L; Michaels, Zachary; Goetz, Jared M; Lemon, Stephenie C; Ma, Yunsheng

2017-01-01

Background Online social networks may be a promising modality to deliver lifestyle interventions by reducing cost and burden. Although online social networks have been integrated as one component of multimodality lifestyle interventions, no randomized trials to date have compared a lifestyle intervention delivered entirely via online social network with a traditional clinic-delivered intervention. Objective This paper describes the design and methods of a noninferiority randomized controlled trial, testing (1) whether a lifestyle intervention delivered entirely through an online social network would produce weight loss that would not be appreciably worse than that induced by a traditional clinic-based lifestyle intervention among overweight and obese adults and (2) whether the former would do so at a lower cost. Methods Adults with body mass index (BMI) between 27 and 45 kg/m2 (N=328) will be recruited from the communities in central Massachusetts. These overweight or obese adults will be randomized to two conditions: a lifestyle intervention delivered entirely via the online social network Twitter (Get Social condition) and an in-person group-based lifestyle intervention (Traditional condition) among overweight and obese adults. Measures will be obtained at baseline, 6 months, and 12 months after randomization. The primary noninferiority outcome is percentage weight loss at 12 months. Secondary noninferiority outcomes include dietary intake and moderate intensity physical activity at 12 months. Our secondary aim is to compare the conditions on cost. Exploratory outcomes include treatment retention, acceptability, and burden. Finally, we will explore predictors of weight loss in the online social network condition. Results The final wave of data collection is expected to conclude in June 2019. Data analysis will take place in the months following and is expected to be complete in September 2019. Conclusions Findings will extend the literature by revealing whether delivering a lifestyle intervention via an online social network is an effective alternative to the traditional modality of clinic visits, given the former might be more scalable and feasible to implement in settings that cannot support clinic-based models. Trial Registration ClinicalTrials.gov NCT02646618; https://clinicaltrials.gov/ct2/show/NCT02646618 (Archived by WebCite at http://www.webcitation.org/6v20waTFW) PMID:29229591

Self-System Therapy for Distress Associated with Persistent Low Back Pain: A Randomized Clinical Trial

PubMed Central

Waters, Sandra J.; McKee, Daphne C.; Campbell, Lisa C.; Shelby, Rebecca A.; Dixon, Kim E.; Fras, Anne Marie; Keefe, Francis J.

2015-01-01

Objective Persistent low back pain (PLBP) is associated with vulnerability to depression. PLBP frequently requires major changes in occupation and lifestyle, which can lead to a sense of failing to attain one’s personal goals (self-discrepancy). Method We conducted a clinical trial to examine the efficacy of self-system therapy (SST), a brief structured therapy for depression based on self-discrepancy theory. A total of 101 patients with PLBP and clinically significant depressive symptoms were randomized either to SST, pain education, or standard care. Results Patients receiving SST showed significantly greater improvement in depressive symptoms. Reduction in self-discrepancy predicted reduction in depressive symptoms only within the SST condition. Conclusions Findings support the utility of SST for individuals facing persistent pain and associated depression. PMID:26079438

Results from the Xylitol for Adult Caries Trial (X-ACT)

PubMed Central

Bader, James D.; Vollmer, William M.; Shugars, Daniel A.; Gilbert, Gregg H.; Amaechi, Bennett T.; Brown, John P.; Laws, Reesa L.; Funkhouser, Kimberly A.; Makhija, Sonia K.; Ritter, André V.; Leo, Michael C.

2013-01-01

Background Although caries is prevalent in adults, few preventive therapies have been tested in adult populations. This randomized clinical trial evaluated the effectiveness of xylitol lozenges in preventing caries in elevated caries-risk adults. Methods X-ACT was a three-site placebo-controlled randomized trial. Participants (n=691) ages 21–80 consumed five 1.0 g xylitol or placebo lozenges daily for 33 months. Clinical examinations occurred at baseline, 12, 24 and 33 months. Results Xylitol lozenges reduced the caries increment 11%. This reduction, which represented less than one-third of a surface per year, was not statistically significant. There was no indication of a dose-response effect. Conclusions Daily use of xylitol lozenges did not result in a statistically or clinically significant reduction in 33-month caries increment among elevated caries-risk adults. Clinical Implications These results suggest that xylitol used as a supplement in adults does not significantly reduce their caries experience. PMID:23283923

Characteristics of clinical trials registered in ClinicalTrials.gov, 2007-2010.

PubMed

Califf, Robert M; Zarin, Deborah A; Kramer, Judith M; Sherman, Rachel E; Aberle, Laura H; Tasneem, Asba

2012-05-02

Recent reports highlight gaps between guidelines-based treatment recommendations and evidence from clinical trials that supports those recommendations. Strengthened reporting requirements for studies registered with ClinicalTrials.gov enable a comprehensive evaluation of the national trials portfolio. To examine fundamental characteristics of interventional clinical trials registered in the ClinicalTrials.gov database. A data set comprising 96,346 clinical studies from ClinicalTrials.gov was downloaded on September 27, 2010, and entered into a relational database to analyze aggregate data. Interventional trials were identified and analyses were focused on 3 clinical specialties-cardiovascular, mental health, and oncology-that together encompass the largest number of disability-adjusted life-years lost in the United States. Characteristics of registered clinical trials as reported data elements in the trial registry; how those characteristics have changed over time; differences in characteristics as a function of clinical specialty; and factors associated with use of randomization, blinding, and data monitoring committees (DMCs). The number of registered interventional clinical trials increased from 28,881 (October 2004-September 2007) to 40,970 (October 2007-September 2010), and the number of missing data elements has generally declined. Most interventional trials registered between 2007 and 2010 were small, with 62% enrolling 100 or fewer participants. Many clinical trials were single-center (66%; 24,788/37,520) and funded by organizations other than industry or the National Institutes of Health (NIH) (47%; 17,592/37,520). Heterogeneity in the reported methods by clinical specialty; sponsor type; and the reported use of DMCs, randomization, and blinding was evident. For example, reported use of DMCs was less common in industry-sponsored vs NIH-sponsored trials (adjusted odds ratio [OR], 0.11; 95% CI, 0.09-0.14), earlier-phase vs phase 3 trials (adjusted OR, 0.83; 95% CI, 0.76-0.91), and mental health trials vs those in the other 2 specialties. In similar comparisons, randomization and blinding were less frequently reported in earlier-phase, oncology, and device trials. Clinical trials registered in ClinicalTrials.gov are dominated by small trials and contain significant heterogeneity in methodological approaches, including reported use of randomization, blinding, and DMCs.

Best strategies to implement clinical pathways in an emergency department setting: study protocol for a cluster randomized controlled trial

PubMed Central

2013-01-01

Background The clinical pathway is a tool that operationalizes best evidence recommendations and clinical practice guidelines in an accessible format for ‘point of care’ management by multidisciplinary health teams in hospital settings. While high-quality, expert-developed clinical pathways have many potential benefits, their impact has been limited by variable implementation strategies and suboptimal research designs. Best strategies for implementing pathways into hospital settings remain unknown. This study will seek to develop and comprehensively evaluate best strategies for effective local implementation of externally developed expert clinical pathways. Design/methods We will develop a theory-based and knowledge user-informed intervention strategy to implement two pediatric clinical pathways: asthma and gastroenteritis. Using a balanced incomplete block design, we will randomize 16 community emergency departments to receive the intervention for one clinical pathway and serve as control for the alternate clinical pathway, thus conducting two cluster randomized controlled trials to evaluate this implementation intervention. A minimization procedure will be used to randomize sites. Intervention sites will receive a tailored strategy to support full clinical pathway implementation. We will evaluate implementation strategy effectiveness through measurement of relevant process and clinical outcomes. The primary process outcome will be the presence of an appropriately completed clinical pathway on the chart for relevant patients. Primary clinical outcomes for each clinical pathway include the following: Asthma—the proportion of asthmatic patients treated appropriately with corticosteroids in the emergency department and at discharge; and Gastroenteritis—the proportion of relevant patients appropriately treated with oral rehydration therapy. Data sources include chart audits, administrative databases, environmental scans, and qualitative interviews. We will also conduct an overall process evaluation to assess the implementation strategy and an economic analysis to evaluate implementation costs and benefits. Discussion This study will contribute to the body of evidence supporting effective strategies for clinical pathway implementation, and ultimately reducing the research to practice gaps by operationalizing best evidence care recommendations through effective use of clinical pathways. Trial registration ClinicalTrials.gov: NCT01815710 PMID:23692634

Comparative effectiveness research and its utility in In-clinic practice

PubMed Central

Dang, Amit; Kaur, Kirandeep

2016-01-01

One of the important components of patient-centered healthcare is comparative effectiveness research (CER), which aims at generating evidence from the real-life setting. The primary purpose of CER is to provide comparative information to the healthcare providers, patients, and policy makers about the standard of care available. This involves research on clinical questions unanswered by the explanatory trials during the regulatory approval process. Main methods of CER involve randomized controlled trials and observational methods. The limitations of these two methods have been overcome with the help of new statistical methods. After the evidence generation, it is equally important to communicate the results to all the interested organizations. CER is beginning to have its impact in the clinical practice as its results become part of the clinical practice guidelines. CER will have far-reaching scientific and financial impact. CER will make both the treating physician and the patient equally responsible for the treatment offered. PMID:26955571

The Rivalry between Simulation and Problem-Based Learning: A Study of Learning Transfer in Physician Assistant Students

ERIC Educational Resources Information Center

Meyer, Kimberly E.

2010-01-01

The purpose of this dissertation was to evaluate learning transfer achieved by physician assistant students comparing two instructional methods, human patient simulation and electronic clinical case studies. This prospective, randomized, mixed-methods study utilized first and second-year physician assistant student volunteers taking a pretest and…

A randomized matched-pairs study of feasibility, acceptability, and effectiveness of systems consultation: a novel implementation strategy for adopting clinical guidelines for Opioid prescribing in primary care.

PubMed

Quanbeck, Andrew; Brown, Randall T; Zgierska, Aleksandra E; Jacobson, Nora; Robinson, James M; Johnson, Roberta A; Deyo, Brienna M; Madden, Lynn; Tuan, Wen-Jan; Alagoz, Esra

2018-01-25

This paper reports on the feasibility, acceptability, and effectiveness of an innovative implementation strategy named "systems consultation" aimed at improving adherence to clinical guidelines for opioid prescribing in primary care. While clinical guidelines for opioid prescribing have been developed, they have not been widely implemented, even as opioid abuse reaches epidemic levels. We tested a blended implementation strategy consisting of several discrete implementation strategies, including audit and feedback, academic detailing, and external facilitation. The study compares four intervention clinics to four control clinics in a randomized matched-pairs design. Each systems consultant aided clinics on implementing the guidelines during a 6-month intervention consisting of monthly site visits and teleconferences/videoconferences. The mixed-methods evaluation employs the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework. Quantitative outcomes are compared using time series analysis. Qualitative methods included focus groups, structured interviews, and ethnographic field techniques. Seven clinics were randomly approached to recruit four intervention clinics. Each clinic designated a project team consisting of six to eight staff members, each with at least one prescriber. Attendance at intervention meetings was 83%. More than 80% of staff respondents agreed or strongly agreed with the statements: "I am more familiar with guidelines for safe opioid prescribing" and "My clinic's workflow for opioid prescribing is easier." At 6 months, statistically significant improvements were noted in intervention clinics in the percentage of patients with mental health screens, treatment agreements, urine drug tests, and opioid-benzodiazepine co-prescribing. At 12 months, morphine-equivalent daily dose was significantly reduced in intervention clinics compared to controls. The cost to deliver the strategy was $7345 per clinic. Adaptations were required to make the strategy more acceptable for primary care. Qualitatively, intervention clinics reported that chronic pain was now treated using approaches similar to those employed for other chronic conditions, such as hypertension and diabetes. The systems consultation implementation strategy demonstrated feasibility, acceptability, and effectiveness in a study involving eight primary care clinics. This multi-disciplinary strategy holds potential to mitigate the prevalence of opioid addiction and ultimately may help to improve implementation of clinical guidelines across healthcare. ClinicalTrials.gov (NCT02433496). https://clinicaltrials.gov/ct2/show/NCT02433496 Registered May 5, 2015.

Randomized clinical trial comparing percutaneous closure of patent foramen ovale (PFO) using the Amplatzer PFO Occluder with medical treatment in patients with cryptogenic embolism (PC-Trial): rationale and design

PubMed Central

2011-01-01

Background Several studies have shown an association of cryptogenic stroke and embolism with patent foramen ovale (PFO), but the question how to prevent further events in such patients is unresolved. Options include antithrombotic treatment with warfarin or antiplatelet agents or surgical or endovascular closure of the PFO. The PC-Trial was set up to compare endovascular closure and best medical treatment for prevention of recurrent events. Methods The PC-Trial is a randomized clinical trial comparing the efficacy of percutaneous closure of the PFO using the Amplatzer PFO occluder with best medical treatment in patients with cryptogenic embolism, i.e. mostly cryptogenic stroke. Warfarin for 6 months followed by antiplatelet agents is recommended as medical treatment. Randomization is stratified according to patients age (<45 versus ≥45 years), presence of atrial septal aneurysm (ASA yes or no) and number of embolic events before randomization (one versus more than one event). Primary endpoints are death, nonfatal stroke and peripheral embolism. Discussion patients were randomized in 29 centers of Europe, Canada, and Australia. Randomization started February 2000. Enrollment of 414 patients was completed in February 2009. All patients will be followed-up longitudinally. Follow-up is maintained until the last enrolled patient is beyond 2.5 years of follow-up (expected in 2011). Trial Registration Trial listed in ClinicalTrials.gov as NCT00166257 and sponsored by AGA Medical, Plymouth, MN, USA PMID:21356042

Latent class instrumental variables: A clinical and biostatistical perspective

PubMed Central

Baker, Stuart G.; Kramer, Barnett S.; Lindeman, Karen S.

2015-01-01

In some two-arm randomized trials, some participants receive the treatment assigned to the other arm as a result of technical problems, refusal of a treatment invitation, or a choice of treatment in an encouragement design. In some before-and-after studies, the availability of a new treatment changes from one time period to this next. Under assumptions that are often reasonable, the latent class instrumental variable (IV) method estimates the effect of treatment received in the aforementioned scenarios involving all-or-none compliance and all-or-none availability. Key aspects are four initial latent classes (sometimes called principal strata) based on treatment received if in each randomization group or time period, the exclusion restriction assumption (in which randomization group or time period is an instrumental variable), the monotonicity assumption (which drops an implausible latent class from the analysis), and the estimated effect of receiving treatment in one latent class (sometimes called efficacy, the local average treatment effect, or the complier average causal effect). Since its independent formulations in the biostatistics and econometrics literatures, the latent class IV method (which has no well-established name) has gained increasing popularity. We review the latent class IV method from a clinical and biostatistical perspective, focusing on underlying assumptions, methodological extensions, and applications in our fields of obstetrics and cancer research. PMID:26239275

The Effect of Sodium Hypochlorite and Chlorhexidine as Irrigant Solutions for Root Canal Disinfection: A Systematic Review of Clinical Trials.

PubMed

Gonçalves, Lucio Souza; Rodrigues, Renata Costa Val; Andrade Junior, Carlos Vieira; Soares, Renata G; Vettore, Mario Vianna

2016-04-01

This systematic review aimed to compare the effectiveness of sodium hypochlorite and chlorhexidine for root canal disinfection during root canal therapy. A literature search for clinical trials was made on the PubMed (MEDLINE), Web of Knowledge, SCOPUS, and Science Direct databases and in the reference lists of the identified articles up to January 2015. Quality assessment of the selected studies was performed according to the Consolidated Standards of Reporting Trials statement. One clinical trial and 4 randomized clinical trials were selected from the 172 articles initially identified. There was heterogeneity in the laboratory methods used to assess the root canal disinfection as well as in the concentrations of the irrigants used. Therefore, meta-analysis was not performed. Two studies reported effective and similar reductions in bacterial levels for both irrigants. Sodium hypochlorite was more effective than chlorhexidine in reducing microorganisms in 1 study, and another reported opposite findings. Both root irrigants were ineffective in eliminating endotoxins from necrotic pulp root canals in 1 study. Trial design and information regarding randomization procedures were not clearly described in the clinical trials. No study compared laboratory results with clinical outcomes. The available evidence on this topic is scarce, and the findings of studies were not consistent. Additional randomized clinical trials using clinical outcomes to compare the use of sodium hypochlorite and chlorhexidine during root canal therapy are needed. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Translating basic behavioral and social science research to clinical application: the EVOLVE mixed methods approach.

PubMed

Peterson, Janey C; Czajkowski, Susan; Charlson, Mary E; Link, Alissa R; Wells, Martin T; Isen, Alice M; Mancuso, Carol A; Allegrante, John P; Boutin-Foster, Carla; Ogedegbe, Gbenga; Jobe, Jared B

2013-04-01

To describe a mixed-methods approach to develop and test a basic behavioral science-informed intervention to motivate behavior change in 3 high-risk clinical populations. Our theoretically derived intervention comprised a combination of positive affect and self-affirmation (PA/SA), which we applied to 3 clinical chronic disease populations. We employed a sequential mixed methods model (EVOLVE) to design and test the PA/SA intervention in order to increase physical activity in people with coronary artery disease (post-percutaneous coronary intervention [PCI]) or asthma (ASM) and to improve medication adherence in African Americans with hypertension (HTN). In an initial qualitative phase, we explored participant values and beliefs. We next pilot tested and refined the intervention and then conducted 3 randomized controlled trials with parallel study design. Participants were randomized to combined PA/SA versus an informational control and were followed bimonthly for 12 months, assessing for health behaviors and interval medical events. Over 4.5 years, we enrolled 1,056 participants. Changes were sequentially made to the intervention during the qualitative and pilot phases. The 3 randomized controlled trials enrolled 242 participants who had undergone PCI, 258 with ASM, and 256 with HTN (n = 756). Overall, 45.1% of PA/SA participants versus 33.6% of informational control participants achieved successful behavior change (p = .001). In multivariate analysis, PA/SA intervention remained a significant predictor of achieving behavior change (p < .002, odds ratio = 1.66), 95% CI [1.22, 2.27], controlling for baseline negative affect, comorbidity, gender, race/ethnicity, medical events, smoking, and age. The EVOLVE method is a means by which basic behavioral science research can be translated into efficacious interventions for chronic disease populations.

The effects of probiotic and synbiotic supplementation on metabolic syndrome indices in adults at risk of type 2 diabetes: study protocol for a randomized controlled trial.

PubMed

Kassaian, Nazila; Aminorroaya, Ashraf; Feizi, Awat; Jafari, Parvaneh; Amini, Masoud

2017-03-29

The incidence of type 2 diabetes, cardiovascular diseases, and obesity has been rising dramatically; however, their pathogenesis is particularly intriguing. Recently, dysbiosis of the intestinal microbiota has emerged as a new candidate that may be linked to metabolic diseases. We hypothesize that selective modulation of the intestinal microbiota by probiotic or synbiotic supplementation may improve metabolic dysfunction and prevent diabetes in prediabetics. In this study, a synthesis and study of synbiotics will be carried out for the first time in Iran. In a randomized triple-blind controlled clinical trial, 120 adults with impaired glucose tolerance based on the inclusion criteria will be selected by a simple random sampling method and will be randomly allocated to 6 months of 6 g/d probiotic, synbiotic or placebo. The fecal abundance of bacteria, blood pressure, height, weight, and waist and hip circumferences will be measured at baseline and following treatment. Also, plasma lipid profiles, HbA1C, fasting plasma glucose, and insulin levels, will be measured and insulin resistance (HOMA-IR) and beta-cell function (HOMA-B) will be calculated at baseline and will be repeated at months 3, 6, 12, and 18. The data will be compared within and between groups using statistical methods. The results of this trial could contribute to the evidence-based clinical guidelines that address gut microbiota manipulation to maximize health benefits in prevention and management of metabolic syndrome in prediabetes. Iranian Registry of Clinical Trials: IRCT201511032321N2 . Registered on 27 February 2016.

A meta-analysis of mammographic screening with and without clinical breast examination

PubMed Central

Hamashima, Chisato; Ohta, Koji; Kasahara, Yoshio; Katayama, Takafumi; Nakayama, Tomio; Honjo, Satoshi; Ohnuki, Koji

2015-01-01

Mammographic screening with clinical breast examination has been recommended in Japan since 2000. Although mammographic screening without clinical breast examination has not been recommended, its introduction is anticipated. The efficacies of mammographic screening with and without clinical breast examination were evaluated based on the results of randomized controlled trials. PubMed and other databases for studies published between 1985 and 2014 were searched. The study design was limited to randomized controlled trials to evaluate mortality reduction from breast cancer. Five studies were eligible for meta-analysis of mammographic screening without clinical breast examination. The relative risk for women aged 40–74 years was 0.75 (95% confidence interval, 0.67–0.83). Three studies evaluated the efficacy of mammographic screening with clinical breast examination. The relative risk for women aged 40–64 years was 0.87 (95% confidence interval, 0.77–0.98). The number needed to invite was always lower in mammographic screening without clinical breast examination than in mammographic screening with clinical breast examination. In both screening methods, the number needed to invite was higher in women aged 40–49 years than in women aged 50–70 years. These results suggest that mammographic screening without clinical breast examination can afford higher benefits to women aged 50 years and over. Although evidence of the efficacy of mammographic screening without clinical breast examination was confirmed based on the results of the randomized controlled trials, a Japanese study is needed to resolve local problems. PMID:25959787

Measuring Workload Demand of Informatics Systems with the Clinical Case Demand Index

PubMed Central

Iyengar, M. Sriram; Rogith, Deevakar; Florez-Arango, Jose F

2017-01-01

Introduction: The increasing use of Health Information Technology (HIT) can add substantially to workload on clinical providers. Current methods for assessing workload do not take into account the nature of clinical cases and the use of HIT tools while solving them. Methods: The Clinical Case Demand Index (CCDI), consisting of a summary score and visual representation, was developed to meet this need. Consistency with current perceived workload measures was evaluated in a Randomized Control Trial of a mobile health system. Results: CCDI is significantly correlated with existing workload measures and inversely related to provider performance. Discussion: CCDI combines subjective and objective characteristics of clinical cases along with cognitive and clinical dimensions. Applications include evaluation of HIT tools, clinician scheduling, medical education. Conclusion: CCDI supports comparative effectiveness research of HIT tools. In addition, CCDI could have numerous applications including training, clinical trials, design of clinical workflows, and others. PMID:29854166

Public Funding for Contraception, Provider Training, and Use of Highly Effective Contraceptives: A Cluster Randomized Trial.

PubMed

Thompson, Kirsten M J; Rocca, Corinne H; Kohn, Julia E; Goodman, Suzan; Stern, Lisa; Blum, Maya; Speidel, J Joseph; Darney, Philip D; Harper, Cynthia C

2016-03-01

We determined whether public funding for contraception was associated with long-acting reversible contraceptive (LARC) use when providers received training on these methods. We evaluated the impact of a clinic training intervention and public funding on LARC use in a cluster randomized trial at 40 randomly assigned clinics across the United States (2011-2013). Twenty intervention clinics received a 4-hour training. Women aged 18 to 25 were enrolled and followed for 1 year (n = 1500: 802 intervention, 698 control). We estimated the effects of the intervention and funding sources on LARC initiation with Cox proportional hazards models with shared frailty. Women at intervention sites had higher LARC initiation than those at control (22 vs 18 per 100 person-years; adjusted hazard ratio [AHR] = 1.43; 95% confidence interval [CI] = 1.04, 1.98). Participants receiving care at clinics with Medicaid family planning expansion programs had almost twice the initiation rate as those at clinics without (25 vs 13 per 100 person-years; AHR = 2.26; 95% CI = 1.59, 3.19). LARC initiation also increased among participants with public (AHR = 1.56; 95% CI = 1.09, 2.22) but not private health insurance. Public funding and provider training substantially improve LARC access.

CNV-RF Is a Random Forest-Based Copy Number Variation Detection Method Using Next-Generation Sequencing.

PubMed

Onsongo, Getiria; Baughn, Linda B; Bower, Matthew; Henzler, Christine; Schomaker, Matthew; Silverstein, Kevin A T; Thyagarajan, Bharat

2016-11-01

Simultaneous detection of small copy number variations (CNVs) (<0.5 kb) and single-nucleotide variants in clinically significant genes is of great interest for clinical laboratories. The analytical variability in next-generation sequencing (NGS) and artifacts in coverage data because of issues with mappability along with lack of robust bioinformatics tools for CNV detection have limited the utility of targeted NGS data to identify CNVs. We describe the development and implementation of a bioinformatics algorithm, copy number variation-random forest (CNV-RF), that incorporates a machine learning component to identify CNVs from targeted NGS data. Using CNV-RF, we identified 12 of 13 deletions in samples with known CNVs, two cases with duplications, and identified novel deletions in 22 additional cases. Furthermore, no CNVs were identified among 60 genes in 14 cases with normal copy number and no CNVs were identified in another 104 patients with clinical suspicion of CNVs. All positive deletions and duplications were confirmed using a quantitative PCR method. CNV-RF also detected heterozygous deletions and duplications with a specificity of 50% across 4813 genes. The ability of CNV-RF to detect clinically relevant CNVs with a high degree of sensitivity along with confirmation using a low-cost quantitative PCR method provides a framework for providing comprehensive NGS-based CNV/single-nucleotide variant detection in a clinical molecular diagnostics laboratory. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Exposing Clinicians to Exposure: A Randomized Controlled Dissemination Trial of Exposure Therapy for Anxiety Disorders

PubMed Central

Harned, Melanie S.; Dimeff, Linda A.; Woodcock, Eric A.; Kelly, Tim; Zavertnik, Jake; Contreras, Ignacio; Danner, Sankirtana M.

2014-01-01

Objective The present study evaluated three technology-based methods of training mental health providers in exposure therapy (ET) for anxiety disorders. Training methods were designed to address common barriers to the dissemination of ET, including limited access to training, negative clinician attitudes toward ET, and lack of support during and following training. Method Clinicians naïve to ET (N=181, Mage = 37.4, 71.3% female, 72.1% Caucasian) were randomly assigned to: 1) an interactive, multimedia online training (OLT), 2) OLT plus a brief, computerized motivational enhancement intervention (OLT+ME), or 3) OLT + ME plus a web-based learning community (OLT+ME+LC). Assessments were completed at baseline, post-training, and 6 and 12 weeks following training. Outcomes include satisfaction, knowledge, self-efficacy, attitudes, self-reported clinical use, and observer-rated clinical proficiency. Results All three training methods led to large and comparable improvements in self-efficacy and clinical use of ET, indicating that OLT alone was sufficient for improving these outcomes. The addition of the ME intervention did not significantly improve outcomes in comparison to OLT alone. Supplementing the OLT with both the ME intervention and the LC significantly improved attitudes and clinical proficiency in comparison to OLT alone. The OLT+ME+LC condition was superior to both other conditions in increasing knowledge of ET. Conclusions Multi-component trainings that address multiple potential barriers to dissemination appear to be most effective in improving clinician outcomes. Technology-based training methods offer a satisfactory, effective, and scalable way to train mental health providers in evidence-based treatments such as ET. PMID:25311284

Exact tests using two correlated binomial variables in contemporary cancer clinical trials.

PubMed

Yu, Jihnhee; Kepner, James L; Iyer, Renuka

2009-12-01

New therapy strategies for the treatment of cancer are rapidly emerging because of recent technology advances in genetics and molecular biology. Although newer targeted therapies can improve survival without measurable changes in tumor size, clinical trial conduct has remained nearly unchanged. When potentially efficacious therapies are tested, current clinical trial design and analysis methods may not be suitable for detecting therapeutic effects. We propose an exact method with respect to testing cytostatic cancer treatment using correlated bivariate binomial random variables to simultaneously assess two primary outcomes. The method is easy to implement. It does not increase the sample size over that of the univariate exact test and in most cases reduces the sample size required. Sample size calculations are provided for selected designs.

Pseudo CT estimation from MRI using patch-based random forest

NASA Astrophysics Data System (ADS)

Yang, Xiaofeng; Lei, Yang; Shu, Hui-Kuo; Rossi, Peter; Mao, Hui; Shim, Hyunsuk; Curran, Walter J.; Liu, Tian

2017-02-01

Recently, MR simulators gain popularity because of unnecessary radiation exposure of CT simulators being used in radiation therapy planning. We propose a method for pseudo CT estimation from MR images based on a patch-based random forest. Patient-specific anatomical features are extracted from the aligned training images and adopted as signatures for each voxel. The most robust and informative features are identified using feature selection to train the random forest. The well-trained random forest is used to predict the pseudo CT of a new patient. This prediction technique was tested with human brain images and the prediction accuracy was assessed using the original CT images. Peak signal-to-noise ratio (PSNR) and feature similarity (FSIM) indexes were used to quantify the differences between the pseudo and original CT images. The experimental results showed the proposed method could accurately generate pseudo CT images from MR images. In summary, we have developed a new pseudo CT prediction method based on patch-based random forest, demonstrated its clinical feasibility, and validated its prediction accuracy. This pseudo CT prediction technique could be a useful tool for MRI-based radiation treatment planning and attenuation correction in a PET/MRI scanner.

[Plaque segmentation of intracoronary optical coherence tomography images based on K-means and improved random walk algorithm].

PubMed

Wang, Guanglei; Wang, Pengyu; Han, Yechen; Liu, Xiuling; Li, Yan; Lu, Qian

2017-06-01

In recent years, optical coherence tomography (OCT) has developed into a popular coronary imaging technology at home and abroad. The segmentation of plaque regions in coronary OCT images has great significance for vulnerable plaque recognition and research. In this paper, a new algorithm based on K -means clustering and improved random walk is proposed and Semi-automated segmentation of calcified plaque, fibrotic plaque and lipid pool was achieved. And the weight function of random walk is improved. The distance between the edges of pixels in the image and the seed points is added to the definition of the weight function. It increases the weak edge weights and prevent over-segmentation. Based on the above methods, the OCT images of 9 coronary atherosclerotic patients were selected for plaque segmentation. By contrasting the doctor's manual segmentation results with this method, it was proved that this method had good robustness and accuracy. It is hoped that this method can be helpful for the clinical diagnosis of coronary heart disease.

Forensic Luminol Blood Test for Preventing Cross-contamination in Dentistry: An Evaluation of a Dental School Clinic

PubMed Central

Bortoluzzi, Marcelo Carlos; Cadore, Peterson; Gallon, Andrea; Imanishi, Soraia Almeida Watanabe

2014-01-01

Background: More than 200 different diseases may be transmitted from exposure to blood in the dental setting. The aim of this study is to identify possible faults in the crosscontamination chain control in a dental school clinic searching for traces of blood in the clinical contact surfaces (CCS) through forensic luminol blood test. Methods: Traces of invisible blood where randomly searched in CCS of one dental school clinic. Results: Forty eight surfaces areas in the CCS were tested and the presence of invisible and remnant blood was identified in 28 (58.3%) items. Conclusions: We suggest that the luminol method is suitable for identifying contamination with invisible blood traces and this method may be a useful tool to prevent cross-contamination in the dental care setting. PMID:25400895

Autoregressive Modeling of Drift and Random Error to Characterize a Continuous Intravascular Glucose Monitoring Sensor.

PubMed

Zhou, Tony; Dickson, Jennifer L; Geoffrey Chase, J

2018-01-01

Continuous glucose monitoring (CGM) devices have been effective in managing diabetes and offer potential benefits for use in the intensive care unit (ICU). Use of CGM devices in the ICU has been limited, primarily due to the higher point accuracy errors over currently used traditional intermittent blood glucose (BG) measures. General models of CGM errors, including drift and random errors, are lacking, but would enable better design of protocols to utilize these devices. This article presents an autoregressive (AR) based modeling method that separately characterizes the drift and random noise of the GlySure CGM sensor (GlySure Limited, Oxfordshire, UK). Clinical sensor data (n = 33) and reference measurements were used to generate 2 AR models to describe sensor drift and noise. These models were used to generate 100 Monte Carlo simulations based on reference blood glucose measurements. These were then compared to the original CGM clinical data using mean absolute relative difference (MARD) and a Trend Compass. The point accuracy MARD was very similar between simulated and clinical data (9.6% vs 9.9%). A Trend Compass was used to assess trend accuracy, and found simulated and clinical sensor profiles were similar (simulated trend index 11.4° vs clinical trend index 10.9°). The model and method accurately represents cohort sensor behavior over patients, providing a general modeling approach to any such sensor by separately characterizing each type of error that can arise in the data. Overall, it enables better protocol design based on accurate expected CGM sensor behavior, as well as enabling the analysis of what level of each type of sensor error would be necessary to obtain desired glycemic control safety and performance with a given protocol.

A Novel Roux-en-Y Reconstruction Involving the Use of Two Circular Staplers after Distal Subtotal Gastrectomy for Gastric Cancer.

PubMed

Hur, Hoon; Ahn, Chang Wook; Byun, Cheul Su; Shin, Ho Jung; Kim, Young Bae; Son, Sang-Yong; Han, Sang-Uk

2017-09-01

Although Roux-en-Y (R-Y) reconstruction after distal gastrectomy has several advantages, such as prevention of bile reflux into the remnant stomach, it is rarely used because of the technical difficulty. This prospective randomized clinical trial aimed to show the efficacy of a novel method of R-Y reconstruction involving the use of 2 circular staplers by comparing this novel method to Billroth-I (B-I) reconstruction. A total of 118 patients were randomly allocated into the R-Y (59 patients) and B-I reconstruction (59 patients) groups. R-Y anastomosis was performed using two circular staplers and no hand sewing. The primary end-point of this clinical trial was the reflux of bile into the remnant stomach evaluated using endoscopic and histological findings at 6 months after surgery. No significant differences in clinicopathological findings were observed between the 2 groups. Although anastomosis time was significantly longer for the patients of the R-Y group (P<0.001), no difference was detected between the 2 groups in terms of the total surgery duration (P=0.112). Endoscopic findings showed a significant reduction of bile reflux in the remnant stomach in the R-Y group (P<0.001), and the histological findings showed that reflux gastritis was more significant in the B-I group than in the R-Y group (P=0.026). The results of this randomized controlled clinical trial showed that compared with B-I reconstruction, R-Y reconstruction using circular staplers is a safe and feasible procedure. This clinical trial study was registered at www.ClinicalTrials.gov (registration No. NCT01142271).

Satisfaction in complete denture wearers with and without adhesives: A randomized, crossover, double-blind clinical trial

PubMed Central

Torres-Sánchez, Carlos; Montoya-Salazar, Vanessa; Gutierrez-Pérez, Jose-Luis; Jimenez-Castellanos, Emilio

2018-01-01

Background The purpose of this study was to compare the satisfaction of patients regarding retention, stability and accumulation of particles with a randomized, double-blind crossed method in users with complete dentures with and without adhesive. Material and Methods Seventeen edentulous individuals were randomized and received new upper and lower complete dentures. After a period of adaptation, they participated in some masticatory tests and clinical revisions, after use the protheses with and without the use of two denture adhesives: Adhesive A (Fittydent, Fittydent International GmbH) and adhesive B (Corega, GlaxoSmithKline) at 0, 7 and 14 days. Satisfaction was measured immediately after each test through a survey using a VAS scale (0-10) and data were analyzed with McNemar’s test with Bonferroni correction. Results The results showed significant differences (p<.01) between the study groups with adhesive A - B and the group without adhesive, but no significant differences were found between the two stickers for any of the variables studied. Conclusions Complete denture adhesives significantly improved the satisfaction of patients because a better retention, stability and less accumulation of particles of the food substitute between the denture and the mucosa is obtained compared with non-use of complete denture adhesives. Key words:Complete dentures, patient satisfaction, denture adhesives, clinical trials. PMID:29946414

Effects of Family-Center Empowerment Model on the Lifestyle of Heart Failure Patients: A Randomized Controlled Clinical Trial

PubMed Central

Rakhshan, Mahnaz; Kordshooli, Khadijeh Rahimi; Ghadakpoor, Soraya

2015-01-01

Background: Cardiovascular diseases are the most prevalent disorders in developed countries and heart failure is the major one among them. This disease is caused by numerous factors and one of the most considerable risk factors is unhealthy lifestyle. So the aim of this research was to study the effect of family-center empowerment model on the lifestyle of heart failure patients. Methods: This is a randomized controlled clinical trial on 70 heart failure patients referring to Hazrate Fatemeh heart clinic in Shiraz. After convenience sampling the patients were divided into two control and intervention groups using block randomization Method. The intervention based on family-center empowerment model was performed during 5 sessions. Research tools are lifestyle and demographic information questionnaires. Results: Both intervention and control groups were similar regarding their demographic information (P>0.001). Before the intervention on lifestyle, all measures of the two groups were equal (P>0.001) but after the intervention; statistically significant differences were reported in all dimensions of lifestyle, the total lifestyle score in the intervention group was 70.09±16.38 and in the control group -6.03±16.36 (P<0.001). Conclusion: Performing the family-center empowerment model for heart failure patients is practically possible, leading to improvement or refinement of their and their families’ lifestyle. Trial Registration Number: IRCT 2014072018468N3 PMID:26448952

Impact of fibrates on circulating cystatin C levels: a systematic review and meta-analysis of clinical trials.

PubMed

Sahebkar, Amirhossein; Simental-Mendía, Luis E; Pirro, Matteo; Montecucco, Fabrizio; Carbone, Federico; Banach, Maciej; Barreto, George E; Butler, Alexandra E

2018-06-29

To assess the effect of fibrates on circulating cystatin C levels. Clinical studies evaluating the effect of a fibrate on circulating cystatin C levels were searched in PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases. A random-effect model and generic inverse variance method were used for quantitative data synthesis, sensitivity analysis conducted using the leave-one-out method, and weighted random-effects meta-regression performed to evaluate potential confounders on cystatin C levels. This meta-analysis of data from 9 published studies (16 treatment arms) involved a total of 2195 subjects. In a single-arm analysis of clinical trials (without control group; 8 studies comprising 14 treatment arms), fibrate therapy increased circulating cystatin C concentrations (WMD: 0.07 mg/dL, 95% CI: 0.04, 0.10, p <0.001; I 2 = 82.66%). When the analysis was restricted to randomized controlled trials (4 studies comprising 6 treatment arms), again elevation of circulating cystatin C levels was observed (WMD: 0.06 mg/L, 95% CI: 0.03, 0.09, p <0.001; I 2 = 42.98%). Elevated cystatin C levels were only seen with fenofibrate, not other fibrates. The results suggest that fenofibrate treatment adversely affects cystatin C levels and might partially explain the limited efficacy of fenofibrate in reducing cardiovascular events.

The effect of berberine on insulin resistance in women with polycystic ovary syndrome: detailed statistical analysis plan (SAP) for a multicenter randomized controlled trial.

PubMed

Zhang, Ying; Sun, Jin; Zhang, Yun-Jiao; Chai, Qian-Yun; Zhang, Kang; Ma, Hong-Li; Wu, Xiao-Ke; Liu, Jian-Ping

2016-10-21

Although Traditional Chinese Medicine (TCM) has been widely used in clinical settings, a major challenge that remains in TCM is to evaluate its efficacy scientifically. This randomized controlled trial aims to evaluate the efficacy and safety of berberine in the treatment of patients with polycystic ovary syndrome. In order to improve the transparency and research quality of this clinical trial, we prepared this statistical analysis plan (SAP). The trial design, primary and secondary outcomes, and safety outcomes were declared to reduce selection biases in data analysis and result reporting. We specified detailed methods for data management and statistical analyses. Statistics in corresponding tables, listings, and graphs were outlined. The SAP provided more detailed information than trial protocol on data management and statistical analysis methods. Any post hoc analyses could be identified via referring to this SAP, and the possible selection bias and performance bias will be reduced in the trial. This study is registered at ClinicalTrials.gov, NCT01138930 , registered on 7 June 2010.

Trends in the application of dynamic allocation methods in multi-arm cancer clinical trials.

PubMed

Pond, Gregory R; Tang, Patricia A; Welch, Stephen A; Chen, Eric X

2010-06-01

Dynamic allocation (DA) methods which attempt to balance baseline prognostic factors between treatment arms, can be used in multi-arm clinical trials to sequentially allocate patients to treatment. Although some experts express concern regarding the validity of inference from trials using DA, others believe DA methods produce more credible results. A review of published multi-arm cancer clinical trials was conducted to explore the frequency of DA use in oncology. Multi-arm phase III clinical trials of at least 100 patients per arm, published in 13 major oncology journals from 1995-2005 were manually reviewed. Information about reported use of DA methods, or randomization via random permuted blocks (PB), was extracted along with trial characteristics. Of 476 published clinical trials, 112 (23.5%) reported using some form of DA method, while 103 (21.6%) reported using PB methods. Most trials (403 or 84.7%) reported stratifying on at least one baseline factor. The mean number of stratification factors was 2.70 per trial, and 78.6% of DA trials reported 3 or more stratification factors compared with 30.2% of non-DA trials (p < 0.001). The frequency of DA use increased over time, with 20.2%, 21.3%, 25.8%, 28.8% and 38.9% of trials reported use in 1995-2001, 2002, 2003, 2004, and 2005, respectively. Use of DA methods was more frequently reported in trials involving an academic co-operative group (28.4% vs. 13.8%), however, no difference was observed between industry-funded and other-funded trials (24.0% vs. 23.2%) or geographical region (19.7% of North American trials, 26.2% of European trials and 21.7% of multinational/other trials). As a retrospective analysis, the true frequency of DA use is likely underreported. Few trials gave complete details of the allocation method used, thus it is possible some manuscripts reported incorrect allocation methods. Journals were selected which were assumed to publish most large, multi-arm clinical trials in cancer from 1995-2005, however, some trials were likely reported in journals other than what was reviewed. DA methods are frequently used in multi-arm cancer clinical trials. The use of DA appears to becoming more common over time and are used more frequently when an academic cooperative group is involved. No relationship between industry funded trials or geographic region and allocation method was observed. Clinical Trials 2010; 7: 227-234. http://ctj.sagepub.com.

Multi-Modal Preemptive Analgesia With Pregabalin, Acetaminophen, Naproxen, and Dextromethorphan in Radical Neck Dissection Surgery: A Randomized Clinical Trial

PubMed Central

Amiri, Hamid Reza; Mirzaei, Mojtaba; Beig Mohammadi, Mohammad Taghi; Tavakoli, Farhad

2016-01-01

Background Preemptive analgesia may be considered as a method not only to alleviate postoperative pain but also to decrease analgesic consumption. Different regimens are suggested, but there is currently no standard. Objectives The aim was to measure the efficacy of preemptive analgesia with pregabalin, acetaminophen, naproxen, and dextromethorphan in radical neck dissection surgery for reducing the intensity of pain and morphine consumption. Patients and Methods This study was conducted as a randomized double-blind clinical trial. Eighty adult patients (18 to 60 years of age) under the American society of anesthesiologists (ASA) physical status I and II undergoing elective radical neck dissection were enrolled. Patients were randomized into two groups of 40 with a simple randomization method. The case group received a combination of 15 mg/kg acetaminophen, 2.5 mg/kg pregabalin, 7 mg/kg naproxen, and 0.3 mg/kg dextromethorphan administered orally one hour prior to surgery. Postoperative pain was assessed with the universal pain assessment tool (UPAT) at 0, 2, 4, 6, 12, and 24 hours after surgery. Subjects received morphine based on postoperative pain control protocol. Total administered morphine doses were noted. Results Postoperative pain rates at 0, 2, 4, 6, 12, and 24 hours after surgery were significantly lower for the case group than the control group (P values = 0.014, 0.003, 0.00, 0.00, and 0.00, respectively). Total morphine doses for the preemptive analgesia group were 45% lower than those of the other group. Side effects were similar for both groups. Conclusions A single preoperative oral dose of pregabalin, acetaminophen, dextromethorphan, and naproxen one hour before surgery is an effective method for reducing postoperative pain and morphine consumption in patients undergoing radical neck dissection. PMID:27843771

Increasing complexity of clinical research in gastroenterology: implications for the training of clinician-scientists.

PubMed

Scott, Frank I; McConnell, Ryan A; Lewis, Matthew E; Lewis, James D

2012-04-01

Significant advances have been made in clinical and epidemiologic research methods over the past 30 years. We sought to demonstrate the impact of these advances on published gastroenterology research from 1980 to 2010. Twenty original clinical articles were randomly selected from each of three journals from 1980, 1990, 2000, and 2010. Each article was assessed for topic, whether the outcome was clinical or physiologic, study design, sample size, number of authors and centers collaborating, reporting of various statistical methods, and external funding. From 1980 to 2010, there was a significant increase in analytic studies, clinical outcomes, number of authors per article, multicenter collaboration, sample size, and external funding. There was increased reporting of P values, confidence intervals, and power calculations, and increased use of large multicenter databases, multivariate analyses, and bioinformatics. The complexity of clinical gastroenterology and hepatology research has increased dramatically, highlighting the need for advanced training of clinical investigators.

Clinical Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder (Bipolar CHOICE): A Pragmatic Trial of Complex Treatment for a Complex Disorder

PubMed Central

Nierenberg, Andrew A.; Sylvia, Louisa G.; Leon, Andrew C.; Reilly-Harrington, Noreen; Shesler, Leah W.; McElroy, Susan L.; Friedman, Edward S.; Thase, Michael E.; Shelton, Richard C.; Bowden, Charles; Tohen, Mauricio; Singh, Vivek; Deckersbach, Thilo; Ketter, Terence; Kocsis, James; McInnis, Melvin G.; Schoenfeld, David; Bobo, William V.; Calabrese, Joseph R.

2015-01-01

Background Classic and second generation antipsychotic mood stabilizers are recommended for treatment of bipolar disorder, yet there are no randomized comparative effectiveness studies that have examined the “real-world” advantages and disadvantages of these medications Purpose We describe the strategic decisions in the design of the Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder (Bipolar CHOICE). This paper outlines the key issues and solutions the investigators faced in designing a clinical trial that would maximize generalizability and inform real-world clinical treatment of bipolar disorder. Methods Bipolar CHOICE was a 6-month, multi-site, prospective, randomized clinical trial of outpatients with bipolar disorder. This study compares the effectiveness of quetiapine versus lithium, each with adjunctive personalized treatments. The co-primary outcomes selected are the overall benefits and harms of the study medications (as measured by the Clinical Global Impression-Efficacy Index) and the Necessary Clinical Adjustments (a measure of the number of medication changes). Secondary outcomes are continuous measures of mood, the Framingham General Cardiovascular Risk Score and the Longitudinal Interval Follow up Evaluation Range of Impaired Functioning Tool. Results The final study design consisted of a single-blind, randomized comparative effectiveness trial of quetiapine versus lithium, plus adjunctive personalized treatment (APT), across ten sites. Other important study considerations included limited exclusion criteria to maximize generalizability, flexible dosing of APT medications to mimic real-world treatment, and an intent-to-treat analysis plan. 482 participants were randomized to the study and 364 completed. Limitations The potential limitations of the study include the heterogeneity of APT, selection of study medications, lack of a placebo-control group, and participants’ ability to pay for study medications. Conclusion We expect that this study will inform our understanding of the benefits and harms of lithium, a classic mood stabilizer, compared to quetiapine, a second generation antipsychotic with broad-spectrum activity in bipolar disorder and will provide an example of a well-designed and well-conducted randomized comparative effectiveness clinical trial. PMID:24346608

[Adequate application of quantitative and qualitative statistic analytic methods in acupuncture clinical trials].

PubMed

Tan, Ming T; Liu, Jian-ping; Lao, Lixing

2012-08-01

Recently, proper use of the statistical methods in traditional Chinese medicine (TCM) randomized controlled trials (RCTs) has received increased attention. Statistical inference based on hypothesis testing is the foundation of clinical trials and evidence-based medicine. In this article, the authors described the methodological differences between literature published in Chinese and Western journals in the design and analysis of acupuncture RCTs and the application of basic statistical principles. In China, qualitative analysis method has been widely used in acupuncture and TCM clinical trials, while the between-group quantitative analysis methods on clinical symptom scores are commonly used in the West. The evidence for and against these analytical differences were discussed based on the data of RCTs assessing acupuncture for pain relief. The authors concluded that although both methods have their unique advantages, quantitative analysis should be used as the primary analysis while qualitative analysis can be a secondary criterion for analysis. The purpose of this paper is to inspire further discussion of such special issues in clinical research design and thus contribute to the increased scientific rigor of TCM research.

A note on variance estimation in random effects meta-regression.

PubMed

Sidik, Kurex; Jonkman, Jeffrey N

2005-01-01

For random effects meta-regression inference, variance estimation for the parameter estimates is discussed. Because estimated weights are used for meta-regression analysis in practice, the assumed or estimated covariance matrix used in meta-regression is not strictly correct, due to possible errors in estimating the weights. Therefore, this note investigates the use of a robust variance estimation approach for obtaining variances of the parameter estimates in random effects meta-regression inference. This method treats the assumed covariance matrix of the effect measure variables as a working covariance matrix. Using an example of meta-analysis data from clinical trials of a vaccine, the robust variance estimation approach is illustrated in comparison with two other methods of variance estimation. A simulation study is presented, comparing the three methods of variance estimation in terms of bias and coverage probability. We find that, despite the seeming suitability of the robust estimator for random effects meta-regression, the improved variance estimator of Knapp and Hartung (2003) yields the best performance among the three estimators, and thus may provide the best protection against errors in the estimated weights.

Forecasting Daily Patient Outflow From a Ward Having No Real-Time Clinical Data

PubMed Central

Tran, Truyen; Luo, Wei; Phung, Dinh; Venkatesh, Svetha

2016-01-01

Background: Modeling patient flow is crucial in understanding resource demand and prioritization. We study patient outflow from an open ward in an Australian hospital, where currently bed allocation is carried out by a manager relying on past experiences and looking at demand. Automatic methods that provide a reasonable estimate of total next-day discharges can aid in efficient bed management. The challenges in building such methods lie in dealing with large amounts of discharge noise introduced by the nonlinear nature of hospital procedures, and the nonavailability of real-time clinical information in wards. Objective Our study investigates different models to forecast the total number of next-day discharges from an open ward having no real-time clinical data. Methods We compared 5 popular regression algorithms to model total next-day discharges: (1) autoregressive integrated moving average (ARIMA), (2) the autoregressive moving average with exogenous variables (ARMAX), (3) k-nearest neighbor regression, (4) random forest regression, and (5) support vector regression. Although the autoregressive integrated moving average model relied on past 3-month discharges, nearest neighbor forecasting used median of similar discharges in the past in estimating next-day discharge. In addition, the ARMAX model used the day of the week and number of patients currently in ward as exogenous variables. For the random forest and support vector regression models, we designed a predictor set of 20 patient features and 88 ward-level features. Results Our data consisted of 12,141 patient visits over 1826 days. Forecasting quality was measured using mean forecast error, mean absolute error, symmetric mean absolute percentage error, and root mean square error. When compared with a moving average prediction model, all 5 models demonstrated superior performance with the random forests achieving 22.7% improvement in mean absolute error, for all days in the year 2014. Conclusions In the absence of clinical information, our study recommends using patient-level and ward-level data in predicting next-day discharges. Random forest and support vector regression models are able to use all available features from such data, resulting in superior performance over traditional autoregressive methods. An intelligent estimate of available beds in wards plays a crucial role in relieving access block in emergency departments. PMID:27444059

Aggregated N-of-1 randomized controlled trials: modern data analytics applied to a clinically valid method of intervention effectiveness.

PubMed

Cushing, Christopher C; Walters, Ryan W; Hoffman, Lesa

2014-03-01

Aggregated N-of-1 randomized controlled trials (RCTs) combined with multilevel modeling represent a methodological advancement that may help bridge science and practice in pediatric psychology. The purpose of this article is to offer a primer for pediatric psychologists interested in conducting aggregated N-of-1 RCTs. An overview of N-of-1 RCT methodology is provided and 2 simulated data sets are analyzed to demonstrate the clinical and research potential of the methodology. The simulated data example demonstrates the utility of aggregated N-of-1 RCTs for understanding the clinical impact of an intervention for a given individual and the modeling of covariates to explain why an intervention worked for one patient and not another. Aggregated N-of-1 RCTs hold potential for improving the science and practice of pediatric psychology.

Development of a manualized protocol of massage therapy for clinical trials in osteoarthritis.

PubMed

Ali, Ather; Kahn, Janet; Rosenberger, Lisa; Perlman, Adam I

2012-10-04

Clinical trial design of manual therapies may be especially challenging as techniques are often individualized and practitioner-dependent. This paper describes our methods in creating a standardized Swedish massage protocol tailored to subjects with osteoarthritis of the knee while respectful of the individualized nature of massage therapy, as well as implementation of this protocol in two randomized clinical trials. The manualization process involved a collaborative process between methodologic and clinical experts, with the explicit goals of creating a reproducible semi-structured protocol for massage therapy, while allowing some latitude for therapists' clinical judgment and maintaining consistency with a prior pilot study. The manualized protocol addressed identical specified body regions with distinct 30- and 60-min protocols, using standard Swedish strokes. Each protocol specifies the time allocated to each body region. The manualized 30- and 60-min protocols were implemented in a dual-site 24-week randomized dose-finding trial in patients with osteoarthritis of the knee, and is currently being implemented in a three-site 52-week efficacy trial of manualized Swedish massage therapy. In the dose-finding study, therapists adhered to the protocols and significant treatment effects were demonstrated. The massage protocol was manualized, using standard techniques, and made flexible for individual practitioner and subject needs. The protocol has been applied in two randomized clinical trials. This manualized Swedish massage protocol has real-world utility and can be readily utilized both in the research and clinical settings. Clinicaltrials.gov NCT00970008 (18 August 2009).

The Effect of Cognitive-Behavioral Therapy versus Treatment as Usual for Anxiety in Children with Autism Spectrum Disorders: A Randomized, Controlled Trial

ERIC Educational Resources Information Center

Storch, Eric A.; Arnold, Elysse B.; Lewin, Adam B.; Nadeau, Josh M.; Jones, Anna M.; De Nadai, Alessandro S.; Mutch, P. Jane; Selles, Robert R.; Ung, Danielle; Murphy, Tanya K.

2013-01-01

Objective: To examine the efficacy of a modular cognitive-behavioral therapy (CBT) protocol relative to treatment as usual (TAU) among children with high-functioning autism spectrum disorders (ASD) and clinically significant anxiety. Method: A total of 45 children (7-11 years of age) with high-functioning ASD and clinically significant anxiety…

Effects of a Brief Multimedia Psychoeducational Intervention on the Attitudes and Interest of Patients With Cancer Regarding Clinical Trial Participation: A Multicenter Randomized Controlled Trial

PubMed Central

Jacobsen, Paul B.; Wells, Kristen J.; Meade, Cathy D.; Quinn, Gwendolyn P.; Lee, Ji-Hyun; Fulp, William J.; Gray, Jhanelle E.; Baz, Rachid C.; Springett, Gregory M.; Levine, Richard M.; Markham, Merry-Jennifer; Schreiber, Fred J.; Cartwright, Thomas H.; Burke, James M.; Siegel, Robert D.; Malafa, Mokenge P.; Sullivan, Daniel

2012-01-01

Purpose The negative attitudes of patients with cancer regarding clinical trials are an important contributor to low participation rates. This study evaluated whether a brief psychoeducational intervention was effective in improving patients' attitudes as well as their knowledge, self-efficacy for decision making, receptivity to receiving more information, and general willingness to participate in clinical trials. Patients and Methods A total of 472 adults with cancer who had not been asked previously to participate in a clinical trial were randomly assigned to receive printed educational information about clinical trials or a psychoeducational intervention that provided similar information and also addressed misperceptions and concerns about clinical trials. The primary (attitudes) and secondary outcomes (knowledge, self-efficacy, receptivity, and willingness) were assessed via patient self-report before random assignment and 7 to 28 days later. Results Patients who received the psychoeducational intervention showed more positive attitudes toward clinical trials (P = .016) and greater willingness to participate (P = .011) at follow-up than patients who received printed educational information. Evidence of an indirect effect of intervention assignment on willingness to participate (estimated at 0.168; 95% CI, 0.088 to 0.248) suggested that the benefits of psychoeducation on willingness to participate were explained by the positive impact of psychoeducation on attitudes toward clinical trials. Conclusion A brief psychoeducational intervention can improve the attitudes of patients with cancer toward clinical trials and thereby increase their willingness to participate in clinical trials. Findings support conducting additional research to evaluate effects of this intervention on quality of decision making and rates of participation among patients asked to enroll onto therapeutic clinical trials. PMID:22614993

To Compare PubMed Clinical Queries and UpToDate in Teaching Information Mastery to Clinical Residents: A Crossover Randomized Controlled Trial

PubMed Central

Sayyah Ensan, Ladan; Faghankhani, Masoomeh; Javanbakht, Anna; Ahmadi, Seyed-Foad; Baradaran, Hamid Reza

2011-01-01

Purpose To compare PubMed Clinical Queries and UpToDate regarding the amount and speed of information retrieval and users' satisfaction. Method A cross-over randomized trial was conducted in February 2009 in Tehran University of Medical Sciences that included 44 year-one or two residents who participated in an information mastery workshop. A one-hour lecture on the principles of information mastery was organized followed by self learning slide shows before using each database. Subsequently, participants were randomly assigned to answer 2 clinical scenarios using either UpToDate or PubMed Clinical Queries then crossed to use the other database to answer 2 different clinical scenarios. The proportion of relevantly answered clinical scenarios, time to answer retrieval, and users' satisfaction were measured in each database. Results Based on intention-to-treat analysis, participants retrieved the answer of 67 (76%) questions using UpToDate and 38 (43%) questions using PubMed Clinical Queries (P<0.001). The median time to answer retrieval was 17 min (95% CI: 16 to 18) using UpToDate compared to 29 min (95% CI: 26 to 32) using PubMed Clinical Queries (P<0.001). The satisfaction with the accuracy of retrieved answers, interaction with UpToDate and also overall satisfaction were higher among UpToDate users compared to PubMed Clinical Queries users (P<0.001). Conclusions For first time users, using UpToDate compared to Pubmed Clinical Querries can lead to not only a higher proportion of relevant answer retrieval within a shorter time, but also a higher users' satisfaction. So, addition of tutoring pre-appraised sources such as UpToDate to the information mastery curricula seems to be highly efficient. PMID:21858142

Comparison of non-surgical treatment methods for patients with lumbar spinal stenosis: protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Lumbar spinal stenosis is the most common reason for spinal surgery in older adults. Previous studies have shown that surgery is effective for severe cases of stenosis, but many patients with mild to moderate symptoms are not surgical candidates. These patients and their providers are seeking effective non-surgical treatment methods to manage their symptoms; yet there is a paucity of comparative effectiveness research in this area. This knowledge gap has hindered the development of clinical practice guidelines for non-surgical treatment approaches for lumbar spinal stenosis. Methods/design This study is a prospective randomized controlled clinical trial that will be conducted from November 2013 through October 2016. The sample will consist of 180 older adults (>60 years) who have both an anatomic diagnosis of stenosis confirmed by diagnostic imaging, and signs/symptoms consistent with a clinical diagnosis of lumbar spinal stenosis confirmed by clinical examination. Eligible subjects will be randomized into one of three pragmatic treatment groups: 1) usual medical care; 2) individualized manual therapy and rehabilitative exercise; or 3) community-based group exercise. All subjects will be treated for a 6-week course of care. The primary subjective outcome is the Swiss Spinal Stenosis Questionnaire, a self-reported measure of pain/function. The primary objective outcome is the Self-Paced Walking Test, a measure of walking capacity. The secondary objective outcome will be a measurement of physical activity during activities of daily living, using the SenseWear Armband, a portable device to be worn on the upper arm for one week. The primary analysis will use linear mixed models to compare the main effects of each treatment group on the changes in each outcome measure. Secondary analyses will include a responder analysis by group and an exploratory analysis of potential baseline predictors of treatment outcome. Discussion Our study should provide evidence that helps to inform patients and providers about the clinical benefits of three non-surgical approaches to the management of lumbar spinal stenosis symptoms. Trial registration ClinicalTrials.gov identifier: NCT01943435 PMID:24872875

Evaluation of Effectiveness and Cost‐Effectiveness of a Clinical Decision Support System in Managing Hypertension in Resource Constrained Primary Health Care Settings: Results From a Cluster Randomized Trial

PubMed Central

Anchala, Raghupathy; Kaptoge, Stephen; Pant, Hira; Di Angelantonio, Emanuele; Franco, Oscar H.; Prabhakaran, D.

2015-01-01

Background Randomized control trials from the developed world report that clinical decision support systems (DSS) could provide an effective means to improve the management of hypertension (HTN). However, evidence from developing countries in this regard is rather limited, and there is a need to assess the impact of a clinical DSS on managing HTN in primary health care center (PHC) settings. Methods and Results We performed a cluster randomized trial to test the effectiveness and cost‐effectiveness of a clinical DSS among Indian adult hypertensive patients (between 35 and 64 years of age), wherein 16 PHC clusters from a district of Telangana state, India, were randomized to receive either a DSS or a chart‐based support (CBS) system. Each intervention arm had 8 PHC clusters, with a mean of 102 hypertensive patients per cluster (n=845 in DSS and 783 in CBS groups). Mean change in systolic blood pressure (SBP) from baseline to 12 months was the primary endpoint. The mean difference in SBP change from baseline between the DSS and CBS at the 12th month of follow‐up, adjusted for age, sex, height, waist, body mass index, alcohol consumption, vegetable intake, pickle intake, and baseline differences in blood pressure, was −6.59 mm Hg (95% confidence interval: −12.18 to −1.42; P=0.021). The cost‐effective ratio for CBS and DSS groups was $96.01 and $36.57 per mm of SBP reduction, respectively. Conclusion Clinical DSS are effective and cost‐effective in the management of HTN in resource‐constrained PHC settings. Clinical Trial Registration URL: http://www.ctri.nic.in. Unique identifier: CTRI/2012/03/002476. PMID:25559011

Financial Management of a Large Multi-site Randomized Clinical Trial

PubMed Central

Sheffet, Alice J.; Flaxman, Linda; Tom, MeeLee; Hughes, Susan E.; Longbottom, Mary E.; Howard, Virginia J.; Marler, John R.; Brott, Thomas G.

2014-01-01

Background The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) received five years’ funding ($21,112,866) from the National Institutes of Health to compare carotid stenting to surgery for stroke prevention in 2,500 randomized participants at 40 sites. Aims Herein we evaluate the change in the CREST budget from a fixed to variable-cost model and recommend strategies for the financial management of large-scale clinical trials. Methods Projections of the original grant’s fixed-cost model were compared to the actual costs of the revised variable-cost model. The original grant’s fixed-cost budget included salaries, fringe benefits, and other direct and indirect costs. For the variable-cost model, the costs were actual payments to the clinical sites and core centers based upon actual trial enrollment. We compared annual direct and indirect costs and per-patient cost for both the fixed and variable models. Differences between clinical site and core center expenditures were also calculated. Results Using a variable-cost budget for clinical sites, funding was extended by no-cost extension from five to eight years. Randomizing sites tripled from 34 to 109. Of the 2,500 targeted sample size, 138 (5.5%) were randomized during the first five years and 1,387 (55.5%) during the no-cost extension. The actual per-patient costs of the variable model were 9% ($13,845) of the projected per-patient costs ($152,992) of the fixed model. Conclusions Performance-based budgets conserve funding, promote compliance, and allow for additional sites at modest additional cost. Costs of large-scale clinical trials can thus be reduced through effective management without compromising scientific integrity. PMID:24661748

Hybrid Simulation in Teaching Clinical Breast Examination to Medical Students.

PubMed

Nassif, Joseph; Sleiman, Abdul-Karim; Nassar, Anwar H; Naamani, Sima; Sharara-Chami, Rana

2017-10-10

Clinical breast examination (CBE) is traditionally taught to third-year medical students using a lecture and a tabletop breast model. The opportunity to clinically practice CBE depends on patient availability and willingness to be examined by students, especially in culturally sensitive environments. We propose the use of a hybrid simulation model consisting of a standardized patient (SP) wearing a silicone breast simulator jacket and hypothesize that this, compared to traditional teaching methods, would result in improved learning. Consenting third-year medical students (N = 82) at a university-affiliated tertiary care center were cluster-randomized into two groups: hybrid simulation (breast jacket + SP) and control (tabletop breast model). Students received the standard lecture by instructors blinded to the randomization, followed by randomization group-based learning and practice sessions. Two weeks later, participants were assessed in an Objective Structured Clinical Examination (OSCE), which included three stations with SPs blinded to the intervention. The SPs graded the students on CBE completeness, and students completed a self-assessment of their performance and confidence during the examination. CBE completeness scores did not differ between the two groups (p = 0.889). Hybrid simulation improved lesion identification grades (p < 0.001) without increasing false positives. Hybrid simulation relieved the fear of missing a lesion on CBE (p = 0.043) and increased satisfaction with the teaching method among students (p = 0.002). As a novel educational tool, hybrid simulation improves the sensitivity of CBE performed by medical students without affecting its specificity. Hybrid simulation may play a role in increasing the confidence of medical students during CBE.

Lifestyle Modification for Resistant Hypertension: The TRIUMPH Randomized Clinical Trial

PubMed Central

Blumenthal, James A.; Sherwood, Andrew; Smith, Patrick J.; Mabe, Stephanie; Watkins, Lana; Lin, Pao-Hwa; Craighead, Linda W.; Babyak, Michael; Tyson, Crystal; Young, Kenlyn; Ashworth, Megan; Kraus, William; Liao, Lawrence; Hinderliter, Alan

2015-01-01

Background Resistant hypertension (RH) is a growing health burden in this country affecting as many as one in five adults being treated for hypertension. RH is associated with increased risk of adverse cardiovascular disease (CVD) events and all-cause mortality. Strategies to reduce blood pressure in this high risk population are a national priority. Methods TRIUMPH is a single site, prospective, randomized clinical trial (RCT) to evaluate the efficacy of a center-based lifestyle intervention consisting of exercise training, reduced sodium and calorie DASH eating plan, and weight management compared to standardized education and physician advice in treating patients with RH. Patients (N=150) will be randomized in a 2:1 ratio to receive either a 4-month supervised lifestyle intervention delivered in the setting of a cardiac rehabilitation center or to a standardized behavioral counseling session to simulate real-world medical practice. The primary end point is clinic blood pressure; secondary endpoints include ambulatory blood pressure and an array of CVD biomarkers including left ventricular hypertrophy, arterial stiffness, baroreceptor reflex sensitivity, insulin resistance, lipids, sympathetic nervous system activity, and inflammatory markers. Lifestyle habits, blood pressure and CVD risk factors also will be measured at one year follow-up. Conclusions The TRIUMPH randomized clinical trial (ClinicalTrials.gov NCT02342808) is designed to test the efficacy of an intensive, center-based lifestyle intervention compared to a standardized education and physician advice counseling session on blood presssure and CVD biomarkers in patients with RH after 4 months of treatment, and will determine whether lifestyle changes can be maintained for a year. PMID:26542509

Randomized controlled trials in dentistry: common pitfalls and how to avoid them.

PubMed

Fleming, Padhraig S; Lynch, Christopher D; Pandis, Nikolaos

2014-08-01

Clinical trials are used to appraise the effectiveness of clinical interventions throughout medicine and dentistry. Randomized controlled trials (RCTs) are established as the optimal primary design and are published with increasing frequency within the biomedical sciences, including dentistry. This review outlines common pitfalls associated with the conduct of randomized controlled trials in dentistry. Common failings in RCT design leading to various types of bias including selection, performance, detection and attrition bias are discussed in this review. Moreover, methods of minimizing and eliminating bias are presented to ensure that maximal benefit is derived from RCTs within dentistry. Well-designed RCTs have both upstream and downstream uses acting as a template for development and populating systematic reviews to permit more precise estimates of treatment efficacy and effectiveness. However, there is increasing awareness of waste in clinical research, whereby resource-intensive studies fail to provide a commensurate level of scientific evidence. Waste may stem either from inappropriate design or from inadequate reporting of RCTs; the importance of robust conduct of RCTs within dentistry is clear. Optimal reporting of randomized controlled trials within dentistry is necessary to ensure that trials are reliable and valid. Common shortcomings leading to important forms or bias are discussed and approaches to minimizing these issues are outlined. Copyright © 2014 Elsevier Ltd. All rights reserved.

Aloe vera herbal dentifrices for plaque and gingivitis control: a systematic review.

PubMed

Dhingra, K

2014-04-01

To evaluate the effectiveness of aloe vera containing herbal dentifrices in improving plaque control and gingival health. A manual and electronic literature (MEDLINE and Cochrane Central Register of Controlled Trials) search was performed up to July 2012, for randomized controlled trials presenting clinical, microbiological, immunological, and patient-centered data for the efficacy of aloe vera herbal dentifrices for controlling plaque and gingival inflammation in patients with gingivitis. From 79 titles and abstracts, eight full-text articles were screened and finally two randomized controlled trials were selected. These randomized controlled trials reported that aloe vera dentifrices were similar in efficacy to control dentifrices in effectively reducing plaque and gingival inflammation in gingivitis patients based on the assessment of clinical, microbiological, and patient-centered treatment outcomes. However, many important details (composition and characteristics of aloe vera and control dentifrices along with appropriate randomization, blinding, and outcomes assessed) were lacking in these trials, and therefore, the quality of reporting and methods was generally flawed with high risk of bias. Even though there are some promising results, the clinical effectiveness of aloe vera herbal dentifrices is not sufficiently defined at present and warrants further investigations based on reporting guidelines of herbal CONSORT statement. © 2013 John Wiley & Sons A/S.

Automated encoding of clinical documents based on natural language processing.

PubMed

Friedman, Carol; Shagina, Lyudmila; Lussier, Yves; Hripcsak, George

2004-01-01

The aim of this study was to develop a method based on natural language processing (NLP) that automatically maps an entire clinical document to codes with modifiers and to quantitatively evaluate the method. An existing NLP system, MedLEE, was adapted to automatically generate codes. The method involves matching of structured output generated by MedLEE consisting of findings and modifiers to obtain the most specific code. Recall and precision applied to Unified Medical Language System (UMLS) coding were evaluated in two separate studies. Recall was measured using a test set of 150 randomly selected sentences, which were processed using MedLEE. Results were compared with a reference standard determined manually by seven experts. Precision was measured using a second test set of 150 randomly selected sentences from which UMLS codes were automatically generated by the method and then validated by experts. Recall of the system for UMLS coding of all terms was .77 (95% CI.72-.81), and for coding terms that had corresponding UMLS codes recall was .83 (.79-.87). Recall of the system for extracting all terms was .84 (.81-.88). Recall of the experts ranged from .69 to .91 for extracting terms. The precision of the system was .89 (.87-.91), and precision of the experts ranged from .61 to .91. Extraction of relevant clinical information and UMLS coding were accomplished using a method based on NLP. The method appeared to be comparable to or better than six experts. The advantage of the method is that it maps text to codes along with other related information, rendering the coded output suitable for effective retrieval.

The Method of Randomization for Cluster-Randomized Trials: Challenges of Including Patients with Multiple Chronic Conditions

PubMed Central

Esserman, Denise; Allore, Heather G.; Travison, Thomas G.

2016-01-01

Cluster-randomized clinical trials (CRT) are trials in which the unit of randomization is not a participant but a group (e.g. healthcare systems or community centers). They are suitable when the intervention applies naturally to the cluster (e.g. healthcare policy); when lack of independence among participants may occur (e.g. nursing home hygiene); or when it is most ethical to apply an intervention to all within a group (e.g. school-level immunization). Because participants in the same cluster receive the same intervention, CRT may approximate clinical practice, and may produce generalizable findings. However, when not properly designed or interpreted, CRT may induce biased results. CRT designs have features that add complexity to statistical estimation and inference. Chief among these is the cluster-level correlation in response measurements induced by the randomization. A critical consideration is the experimental unit of inference; often it is desirable to consider intervention effects at the level of the individual rather than the cluster. Finally, given that the number of clusters available may be limited, simple forms of randomization may not achieve balance between intervention and control arms at either the cluster- or participant-level. In non-clustered clinical trials, balance of key factors may be easier to achieve because the sample can be homogenous by exclusion of participants with multiple chronic conditions (MCC). CRTs, which are often pragmatic, may eschew such restrictions. Failure to account for imbalance may induce bias and reducing validity. This article focuses on the complexities of randomization in the design of CRTs, such as the inclusion of patients with MCC, and imbalances in covariate factors across clusters. PMID:27478520

Methods to Limit Attrition in Longitudinal Comparative Effectiveness Trials: Lessons from the Lithium Use for Bipolar Disorder (LiTMUS) Study

PubMed Central

Sylvia, Louisa G.; Reilly-Harrington, Noreen A.; Leon, Andrew C.; Kansky, Christine I.; Ketter, Terence A.; Calabrese, Joseph R.; Thase, Michael E.; Bowden, Charles L.; Friedman, Edward S.; Ostacher, Michael J.; Iosifescu, Dan V.; Severe, Joanne; Nierenberg, Andrew A.

2013-01-01

Background High attrition rates which occur frequently in longitudinal clinical trials of interventions for bipolar disorder limit the interpretation of results. Purpose The aim of this article is to present design approaches that limited attrition in the Lithium Use for Bipolar Disorder (LiTMUS) Study. Methods LiTMUS was a 6-month randomized, longitudinal multi-site comparative effectiveness trial that examined bipolar participants who were at least mildly ill. Participants were randomized to either low to moderate doses of lithium or no lithium, in addition to other treatments needed for mood stabilization administered in a guideline-informed, empirically supported, and personalized fashion (N=283). Results Components of the study design that may have contributed to the low attrition rate of the study included use of: (1) an intent-to-treat design; (2) a randomized adjunctive single-blind design; (3) participant reimbursement; (4) intent-to-attend the next study visit (includes a discussion of attendance obstacles when intention is low); (5) quality care with limited participant burden; and (6) target windows for study visits. Limitations Site differences and the effectiveness and tolerability data have not been analyzed yet. Conclusions These components of the LiTMUS study design may have reduced the probability of attrition which would inform the design of future randomized clinical effectiveness trials. PMID:22076437

Methods for a multicenter randomized trial for mixed urinary incontinence: rationale and patient-centeredness of the ESTEEM trial.

PubMed

Sung, Vivian W; Borello-France, Diane; Dunivan, Gena; Gantz, Marie; Lukacz, Emily S; Moalli, Pamela; Newman, Diane K; Richter, Holly E; Ridgeway, Beri; Smith, Ariana L; Weidner, Alison C; Meikle, Susan

2016-10-01

Mixed urinary incontinence (MUI) can be a challenging condition to manage. We describe the protocol design and rationale for the Effects of Surgical Treatment Enhanced with Exercise for Mixed Urinary Incontinence (ESTEEM) trial, designed to compare a combined conservative and surgical treatment approach versus surgery alone for improving patient-centered MUI outcomes at 12 months. ESTEEM is a multisite, prospective, randomized trial of female participants with MUI randomized to a standardized perioperative behavioral/pelvic floor exercise intervention plus midurethral sling versus midurethral sling alone. We describe our methods and four challenges encountered during the design phase: defining the study population, selecting relevant patient-centered outcomes, determining sample size estimates using a patient-reported outcome measure, and designing an analysis plan that accommodates MUI failure rates. A central theme in the design was patient centeredness, which guided many key decisions. Our primary outcome is patient-reported MUI symptoms measured using the Urogenital Distress Inventory (UDI) score at 12 months. Secondary outcomes include quality of life, sexual function, cost-effectiveness, time to failure, and need for additional treatment. The final study design was implemented in November 2013 across eight clinical sites in the Pelvic Floor Disorders Network. As of 27 February 2016, 433 total/472 targeted participants had been randomized. We describe the ESTEEM protocol and our methods for reaching consensus for methodological challenges in designing a trial for MUI by maintaining the patient perspective at the core of key decisions. This trial will provide information that can directly impact patient care and clinical decision making.

The Recruitment Experience of a Randomized Clinical Trial to Aid Young Adult Smokers to Stop Smoking without Weight Gain with Interactive Technology.

PubMed

Coday, Mace; Richey, Phyllis; Thomas, Fridtjof; Tran, Quynh T; Terrell, Sarah B; Tylavsky, Fran; Miro, Danielle; Caufield, Margaret; Johnson, Karen C

2016-04-15

Multiple recruitment strategies are often needed to recruit an adequate number of participants, especially hard to reach groups. Technology-based recruitment methods hold promise as a more robust form of reaching and enrolling historically hard to reach young adults. The TARGIT study is a randomized two-arm clinical trial in young adults using interactive technology testing an efficacious proactive telephone Quitline versus the Quitline plus a behavioral weight management intervention focusing on smoking cessation and weight change. All randomized participants in the TARGIT study were required to be a young adult smoker (18-35 years), who reported smoking at least 10 cigarettes per day, had a BMI < 40 kg/m 2, and were willing to stop smoking and not gain weight. Traditional recruitment methods were compared to technology-based strategies using standard descriptive statistics based on counts and proportions to describe the recruitment process from initial pre-screening (PS) to randomization into TARGIT. Participants at PS were majority Black (59.80%), female (52.66%), normal or over weight (combined 62.42%), 29.5 years old, and smoked 18.4 cigarettes per day. There were differences in men and women with respect to reasons for ineligibility during PS (p < 0.001; ignoring gender specific pregnancy-related ineligibility). TARGIT experienced a disproportionate loss of minorities during recruitment as well as a prolonged recruitment period due to either study ineligibility or not completing screening activities. Recruitment into longer term behavioral change intervention trials can be challenging and multiple methods are often required to recruit hard to reach groups.

Efficacy and safety of cross-cylinder photorefractive keratectomy versus single method in medium-high astigmatism: a randomized clinical trial.

PubMed

Sedghipour, Mohammad R; Lotfi, Afshin; Sadeghilar, Ayaz; Banan, Saeeid

2012-09-07

BACKGROUND: To compare efficacy and safety of photorefractive keratectomy (PRK) by cross-cylinder with single methods in medium-high astigmatism. DESIGN: Randomized clinical trial study PARTICIPANTS: Fifty patients with medium-high compound myopic astigmatism were enrolled between September 2007 and September 2008. METHODS: PRK was performed on 100 eyes of 50 patients with compound myopic astigmatism. Each patient underwent PRK by cross-cylinder approach in one eye and single method on the contralateral eye. Vector analysis was used to assess astigmatic results. MAIN OUTCOME MEASURES: Improvement of visual acuity (snelen chart), refraction, aberrometry. RESULTS: Uncorrected visual acuity (UCCA) equal to 20/40 or better after six months, was achieved in 98% of eyes in the cross-cylinder method versus 96% in single method.. Mean preoperative spherical equivalent(SE) was -5.2 ±2.1 D in the cross-cylinder method versus -5.1 ±0.5 D in the single method. At six months, the mean SE was - 0.5±0.4 D and -0.6±0.3 D, respectively. Mean IOS was 0.4±0.3 in the cross-cylinder group and 0.4±0.4 in the single group. Mean postoperative absolute change in total root-mean-square higher order aberrations in the cross-cylinder group and single group were 0.16 pm and 0.17 pm, respectively. Any of the mentioned differences didn't appear to be statistically significant. CONCLUSIONS: Both PRK methods appeared to be safe and effective in correcting medium-high astigmatism. © 2012 The Author. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.

Costs of revascularization over eight years in the randomized and eligible patients in the Emory Angioplasty versus Surgery Trial (EAST).

PubMed

Weintraub, W S; Becker, E R; Mauldin, P D; Culler, S; Kosinski, A S; King, S B

2000-10-01

The Emory Angioplasty versus Surgery Trial (EAST) was a randomized trial that compared, by intention to treat, the clinical outcome and costs of percutaneous transluminal coronary angioplasty (PTCA) and coronary bypass grafting (CABG) for multivessel coronary artery disease. We present the findings of the economic analysis of EAST through 8 years of follow-up and compare the cost and outcomes of patients randomized in EAST versus patients eligible but not randomized (registry patients). Charges were assessed from hospital UB82 and UB92 bills and professional charges from the Emory Clinic. Hospital charges were reduced to cost through step-down accounting methods. All costs and charges were inflated to 1997 dollars. Costs were assessed for initial hospitalization and for cumulative costs of the initial hospitalization and additional revascularization procedures up to 8 years. Total 8-year costs were $46,548 for CABG and $44,491 for PTCA (p = 0.37). Cost of CABG in the eligible registry group showed a pattern similar to that for randomized patients, but total cost of PTCA was lower for registry patients than for randomized patients. Thus, the primary procedural costs of CABG are more than those for PTCA; this cost advantage, given the limits of measurement, is largely or even completely lost for randomized patients over the course of 8 years because of additional procedures after a first revascularization by PTCA.

Establishing Evidence-Based Indications for Proton Therapy: An Overview of Current Clinical Trials

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

Mishra, Mark V., E-mail: mmishra@umm.edu; Aggarwal, Sameer; Bentzen, Soren M.

Purpose: To review and assess ongoing proton beam therapy (PBT) clinical trials and to identify major gaps. Methods and Materials: Active PBT clinical trials were identified from (clinicaltrials.gov) and the World Health Organization International Clinical Trials Platform Registry. Data on clinical trial disease site, age group, projected patient enrollment, expected start and end dates, study type, and funding source were extracted. Results: A total of 122 active PBT clinical trials were identified, with target enrollment of >42,000 patients worldwide. Ninety-six trials (79%), with a median planned sample size of 68, were classified as interventional studies. Observational studies accounted for 21% ofmore » trials but 71% (n=29,852) of planned patient enrollment. The most common PBT clinical trials focus on gastrointestinal tract tumors (21%, n=26), tumors of the central nervous system (15%, n=18), and prostate cancer (12%, n=15). Five active studies (lung, esophagus, head and neck, prostate, breast) will randomize patients between protons and photons, and 3 will randomize patients between protons and carbon ion therapy. Conclusions: The PBT clinical trial portfolio is expanding rapidly. Although the majority of ongoing studies are interventional, the majority of patients will be accrued to observational studies. Future efforts should focus on strategies to encourage optimal patient enrollment and retention, with an emphasis on randomized, controlled trials, which will require support from third-party payers. Results of ongoing PBT studies should be evaluated in terms of comparative effectiveness, as well as incremental effectiveness and value offered by PBT in comparison with conventional radiation modalities.« less

Role of Statistical Random-Effects Linear Models in Personalized Medicine.

PubMed

Diaz, Francisco J; Yeh, Hung-Wen; de Leon, Jose

2012-03-01

Some empirical studies and recent developments in pharmacokinetic theory suggest that statistical random-effects linear models are valuable tools that allow describing simultaneously patient populations as a whole and patients as individuals. This remarkable characteristic indicates that these models may be useful in the development of personalized medicine, which aims at finding treatment regimes that are appropriate for particular patients, not just appropriate for the average patient. In fact, published developments show that random-effects linear models may provide a solid theoretical framework for drug dosage individualization in chronic diseases. In particular, individualized dosages computed with these models by means of an empirical Bayesian approach may produce better results than dosages computed with some methods routinely used in therapeutic drug monitoring. This is further supported by published empirical and theoretical findings that show that random effects linear models may provide accurate representations of phase III and IV steady-state pharmacokinetic data, and may be useful for dosage computations. These models have applications in the design of clinical algorithms for drug dosage individualization in chronic diseases; in the computation of dose correction factors; computation of the minimum number of blood samples from a patient that are necessary for calculating an optimal individualized drug dosage in therapeutic drug monitoring; measure of the clinical importance of clinical, demographic, environmental or genetic covariates; study of drug-drug interactions in clinical settings; the implementation of computational tools for web-site-based evidence farming; design of pharmacogenomic studies; and in the development of a pharmacological theory of dosage individualization.

A Randomized Study of a Method for Optimizing Adolescent Assent to Biomedical Research

PubMed Central

Annett, Robert D.; Brody, Janet L.; Scherer, David G.; Turner, Charles W.; Dalen, Jeanne; Raissy, Hengameh

2018-01-01

Purpose Voluntary consent/assent with adolescents invited to participate in research raises challenging problems. No studies to date have attempted to manipulate autonomy in relation to assent/consent processes. This study evaluated the effects of an autonomy-enhanced individualized assent/consent procedure embedded within a randomized pediatric asthma clinical trial. Methods Families were randomly assigned to remain together or separated during a consent/assent process, the latter we characterize as an autonomy-enhanced assent/consent procedure. We hypothesized that separating adolescents from their parents would improve adolescent assent by increasing knowledge and appreciation of the clinical trial and willingness to participate. Results 64 adolescent-parent dyads completed procedures. The together versus separate randomization made no difference in adolescent or parent willingness to participate. However, significant differences were found in both parent and adolescent knowledge of the asthma clinical trial based on the assent/consent procedure and adolescent age. The separate assent/consent procedure improved knowledge of study risks and benefits for older adolescents and their parents but not for the younger youth or their parents. Regardless of the assent/consent process, younger adolescents had lower comprehension of information associated with the study medication and research risks and benefits, but not study procedures or their research rights and privileges. Conclusions The use of an autonomy-enhanced assent/consent procedure for adolescents may improve their and their parent’s informed assent/consent without impacting research participation decisions. Traditional assent/consent procedures may result in a “diffusion of responsibility” effect between parents and older adolescents, specifically in attending to key information associated with study risks and benefits. PMID:28949898

Recruitment strategies for an acupuncture randomized clinical trial of reproductive age women

PubMed Central

Pastore, Lisa M.; Dalal, Parchayi

2009-01-01

Summary Objectives To assess the most effective recruitment strategies for an acupuncture clinical trial of reproductive age women. Design The underlying study is an acupuncture randomized clinical trial for an ovulatory disorder that affects approximately 6.5% of reproductive age women (Polycystic Ovary Syndrome). Study participation involved 2 months of intervention and 3 months of follow-up with US$170 compensation. Success of each recruitment method used during the first 37 study months was analyzed. Setting Clinical trial in the Dept. of OB/GYN at the University of Virginia, US. The original geographic residency target was an 80 mile radius around a college town in Virginia (population 155,000), and was expanded to the state capital (population 850,000) in recruitment year 2. Main outcome measures Number of study inquiries (phone calls or emails) over time and by recruitment source. Results In the first 37 months of recruitment (Jan 2006 – Jan 2009), there were 800 study inquiries (582 by phone, 218 by email), of which 749 were screened via telephone questionnaire. The most successful recruitment methods were flyers (28% of inquiries and 26 % of participants) and direct mailing to targeted zip codes (26% and 27%, respectively). The direct mailing cost US$110/inquiry, while the flyers cost less than US$300 in total. Study inquiries were least likely in May and November. Almost all prospective participants (94%) were acupuncture-naïve. Conclusions Posters/flyers and direct mailings proved to be the most successful recruitment methods for this CAM study. Active recruitment with multiple methods was needed for continual enrollment. PMID:19632551

Development and evaluation of an interactive dental video game to teach dentin bonding.

PubMed

Amer, Rafat S; Denehy, Gerald E; Cobb, Deborah S; Dawson, Deborah V; Cunningham-Ford, Marsha A; Bergeron, Cathia

2011-06-01

Written and clinical tests compared the change in clinical knowledge and practical clinical skill of first-year dental students watching a clinical video recording of the three-step etch-and-rinse resin bonding system to those using an interactive dental video game teaching the same procedure. The research design was a randomized controlled trial with eighty first-year dental students enrolled in the preclinical operative dentistry course. Students' change in knowledge was measured through written examination using a pre-test and a post-test, as well as clinical tests in the form of a benchtop shear bond strength test. There was no statistically significant difference between teaching methods in regards to change in either knowledge or clinical skills, with one minor exception relating to the wetness of dentin following etching. Students expressed their preference for an interactive self-paced method of teaching.

Practical considerations for estimating clinical trial accrual periods: application to a multi-center effectiveness study

PubMed Central

Carter, Rickey E; Sonne, Susan C; Brady, Kathleen T

2005-01-01

Background Adequate participant recruitment is vital to the conduct of a clinical trial. Projected recruitment rates are often over-estimated, and the time to recruit the target population (accrual period) is often under-estimated. Methods This report illustrates three approaches to estimating the accrual period and applies the methods to a multi-center, randomized, placebo controlled trial undergoing development. Results Incorporating known sources of accrual variation can yield a more justified estimate of the accrual period. Simulation studies can be incorporated into a clinical trial's planning phase to provide estimates for key accrual summaries including the mean and standard deviation of the accrual period. Conclusion The accrual period of a clinical trial should be carefully considered, and the allocation of sufficient time for participant recruitment is a fundamental aspect of planning a clinical trial. PMID:15796782

The best marketing strategy in aesthetic plastic surgery: evaluating patients' preferences by conjoint analysis.

PubMed

Marsidi, Nick; van den Bergh, Maurice W H M; Luijendijk, Roland W

2014-01-01

To provide the best marketing strategy for a private clinic, knowledge of patients' preferences is essential. In marketing, conjoint analysis has been frequently used to calculate which attributes of a product are most valuable to consumers. This study investigates the relative importance of attributes that influence the selection and decision-making process when choosing an aesthetic private clinic, using conjoint analysis. The following attributes were chosen by the senior author (R.W.L.) and a marketing and communications director after a preselection of 25 randomly selected people: relative cost of the procedure, travel time, experience of the plastic surgeon, size of the clinic, method of referral, and online presentation. The attributes were then divided into levels. Using a random factor conducted by SPSS, 18 different scenarios were created and rated online by 150 potential patients before their potential visit or consultation. The patients could rate these scenarios on a scale from 1 to 7 with respect to the likeliness of visiting the clinic. The most important attribute was experience of the surgeon (35.6 percent), followed by method of referral (21.5 percent), travel time (14.2 percent), cost of procedure (12.9 percent), online presentation (9.7 percent), and size of the clinic (6.1 percent). Six of 16 levels gave a negative influence on the decision making. The authors' study shows that the two most important attributes are the experience of the surgeon and the method of referral and that conjoint analysis is effective in determining patients' preferences. It also shows which levels positively or negatively contribute per attribute.

Evaluation of the Clinical LOINC (Logical Observation Identifiers, Names, and Codes) Semantic Structure as a Terminology Model for Standardized Assessment Measures

PubMed Central

Bakken, Suzanne; Cimino, James J.; Haskell, Robert; Kukafka, Rita; Matsumoto, Cindi; Chan, Garrett K.; Huff, Stanley M.

2000-01-01

Objective: The purpose of this study was to test the adequacy of the Clinical LOINC (Logical Observation Identifiers, Names, and Codes) semantic structure as a terminology model for standardized assessment measures. Methods: After extension of the definitions, 1,096 items from 35 standardized assessment instruments were dissected into the elements of the Clinical LOINC semantic structure. An additional coder dissected at least one randomly selected item from each instrument. When multiple scale types occurred in a single instrument, a second coder dissected one randomly selected item representative of each scale type. Results: The results support the adequacy of the Clinical LOINC semantic structure as a terminology model for standardized assessments. Using the revised definitions, the coders were able to dissect into the elements of Clinical LOINC all the standardized assessment items in the sample instruments. Percentage agreement for each element was as follows: component, 100 percent; property, 87.8 percent; timing, 82.9 percent; system/sample, 100 percent; scale, 92.6 percent; and method, 97.6 percent. Discussion: This evaluation was an initial step toward the representation of standardized assessment items in a manner that facilitates data sharing and re-use. Further clarification of the definitions, especially those related to time and property, is required to improve inter-rater reliability and to harmonize the representations with similar items already in LOINC. PMID:11062226

Latent class instrumental variables: a clinical and biostatistical perspective.

PubMed

Baker, Stuart G; Kramer, Barnett S; Lindeman, Karen S

2016-01-15

In some two-arm randomized trials, some participants receive the treatment assigned to the other arm as a result of technical problems, refusal of a treatment invitation, or a choice of treatment in an encouragement design. In some before-and-after studies, the availability of a new treatment changes from one time period to this next. Under assumptions that are often reasonable, the latent class instrumental variable (IV) method estimates the effect of treatment received in the aforementioned scenarios involving all-or-none compliance and all-or-none availability. Key aspects are four initial latent classes (sometimes called principal strata) based on treatment received if in each randomization group or time period, the exclusion restriction assumption (in which randomization group or time period is an instrumental variable), the monotonicity assumption (which drops an implausible latent class from the analysis), and the estimated effect of receiving treatment in one latent class (sometimes called efficacy, the local average treatment effect, or the complier average causal effect). Since its independent formulations in the biostatistics and econometrics literatures, the latent class IV method (which has no well-established name) has gained increasing popularity. We review the latent class IV method from a clinical and biostatistical perspective, focusing on underlying assumptions, methodological extensions, and applications in our fields of obstetrics and cancer research. Copyright © 2015 John Wiley & Sons, Ltd.

The Effects of Kangaroo Mother Care and Swaddling on Venipuncture Pain in Premature Neonates: A Randomized Clinical Trial.

PubMed

Dezhdar, Shahin; Jahanpour, Faezeh; Firouz Bakht, Saeedeh; Ostovar, Afshin

2016-04-01

Hospitalized premature babies often undergo various painful procedures. Kangaroo mother care (KMC) and swaddling are two pain reduction methods. This study was undertaken to compare the effects of swaddling and KMC on pain during venous sampling in premature neonates. This study was performed as a randomized clinical trial on 90 premature neonates. The neonates were divided into three groups using a random allocation block. The three groups were group A (swaddling), group B (KMC), and group C (control). In all three groups, the heart rate and arterial oxygen saturation were measured and recorded in time intervals of 30 seconds before, during, and 30, 60, 90, and 120 seconds after blood sampling. The neonate's face was video recorded and assessed using the premature infant pain profile (PIPP) at time intervals of 30 seconds. The data was analyzed using the t-test, chi-square test, Repeated Measure analysis of variance (ANOVA), Kruskal-Wallis, Post-hoc, and Bonferroni test. The findings revealed that pain was reduced to a great extent in the swaddling and KMC methods compared to the control group. However, there was no significant difference between KMC and swaddling (P ≥ 0.05). The results of this study indicate that there is no meaningful difference between swaddling and KMC on physiological indexes and pain in neonates. Therefore, the swaddling method may be a good substitute for KMC.

Androgen-deprivation therapy plus chemotherapy in metastatic hormone-sensitive prostate cancer. A systematic review and meta-analysis of randomized clinical trials.

PubMed

Ramos-Esquivel, Allan; Fernández, Cristina; Zeledón, Zenén

2016-08-01

To assess the efficacy and toxicity of androgen-deprivation therapy (ADT) plus chemotherapy in patients with hormone-sensitive metastatic prostate cancer. Randomized clinical trials were identified after systematic searching of databases and conference proceedings. A random-effect model was used to determine the pooled hazard ratio (HR) for the efficacy outcomes-overall survival (OS), biochemical progression-free survival (PFS), and clinical PFS, according to the inverse-variance method. Heterogeneity was measured using the Q and I(2) statistics. A narrative review was done to explore the major adverse drug reactions reported for each trial. After systematic searching, we included 6 trials (n = 2,675) in this meta-analysis. Estramustine-based chemotherapy plus ADT was not associated with improved OS (HR = 0.64; 95% CI: 0.22-1.89; P = 0.42). In contrast, docetaxel plus ADT was associated with improved OS (HR = 0.75; 95% CI: 0.61-0.91; P = 0.004) and clinical PFS (HR = 0.64; 95% CI: 0.57-0.72; P<0.00001). There was no significant heterogeneity detected among trials. Regarding adverse drug reactions grade 3 or higher, neutropenia was the most frequent side effect reported in a range from 12% to 32%. The addition of docetaxel-based chemotherapy to ADT improves OS and clinical PFS in hormone-sensitive metastatic prostate cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Stock Versus CAD/CAM Customized Zirconia Implant Abutments – Clinical and Patient‐Based Outcomes in a Randomized Controlled Clinical Trial

PubMed Central

Meijer, Henny J.A.; Kerdijk, Wouter; Raghoebar, Gerry M.; Cune, Marco

2016-01-01

Abstract Background Single‐tooth replacement often requires a prefabricated dental implant and a customized crown. The benefits of individualization of the abutment remain unclear. Purpose This randomized controlled clinical trial aims to study potential benefits of individualization of zirconia implant abutments with respect to preservation of marginal bone level and several clinical and patient‐based outcome measures. Material and Methods Fifty participants with a missing premolar were included and randomly assigned to standard (ZirDesign, DentsplySirona Implants, Mölndal, Sweden) or computer aided design/computer aided manufacturing (CAD/CAM) customized (Atlantis, DentsplySirona Implants, Mölndal, Sweden) zirconia abutment therapy. Peri‐implant bone level (primary outcome), Plaque‐index, calculus formation, bleeding on probing, gingiva index, probing pocket depth, recession, appearance of soft tissues and patients' contentment were assessed shortly after placement and one year later. Results No implants were lost and no complications related to the abutments were observed. Statistically significant differences between stock and CAD/CAM customized zirconia abutments could not be demonstrated for any of the operationalized variables. Conclusion The use of a CAD/CAM customized zirconia abutment in single tooth replacement of a premolar is not associated with an improvement in clinical performance or patients' contentment when compared to the use of a stock zirconia abutment. PMID:27476829

Structural Alteration of Gut Microbiota during the Amelioration of Human Type 2 Diabetes with Hyperlipidemia by Metformin and a Traditional Chinese Herbal Formula: a Multicenter, Randomized, Open Label Clinical Trial

PubMed Central

2018-01-01

ABSTRACT Accumulating evidence implicates gut microbiota as promising targets for the treatment of type 2 diabetes mellitus (T2DM). With a randomized clinical trial, we tested the hypothesis that alteration of gut microbiota may be involved in the alleviation of T2DM with hyperlipidemia by metformin and a specifically designed herbal formula (AMC). Four hundred fifty patients with T2DM and hyperlipidemia were randomly assigned to either the metformin- or AMC-treated group. After 12 weeks of treatment, 100 patients were randomly selected from each group and assessed for clinical improvement. The effects of the two drugs on the intestinal microbiota were evaluated by analyzing the V3 and V4 regions of the 16S rRNA gene by Illumina sequencing and multivariate statistical methods. Both metformin and AMC significantly alleviated hyperglycemia and hyperlipidemia and shifted gut microbiota structure in diabetic patients. They significantly increased a coabundant group represented by Blautia spp., which significantly correlated with the improvements in glucose and lipid homeostasis. However, AMC showed better efficacies in improving homeostasis model assessment of insulin resistance (HOMA-IR) and plasma triglyceride and also exerted a larger effect on gut microbiota. Furthermore, only AMC increased the coabundant group represented by Faecalibacterium spp., which was previously reported to be associated with the alleviation of T2DM in a randomized clinical trial. Metformin and the Chinese herbal formula may ameliorate type 2 diabetes with hyperlipidemia via enriching beneficial bacteria, such as Blautia and Faecalibacterium spp. PMID:29789365

An Empirically Derived Taxonomy for Personality Diagnosis: Bridging Science and Practice in Conceptualizing Personality

PubMed Central

Westen, Drew; Shedler, Jonathan; Bradley, Bekh; DeFife, Jared A.

2013-01-01

Objective The authors describe a system for diagnosing personality pathology that is empirically derived, clinically relevant, and practical for day-to-day use. Method A random national sample of psychiatrists and clinical psychologists (N=1,201) described a randomly selected current patient with any degree of personality dysfunction (from minimal to severe) using the descriptors in the Shedler-Westen Assessment Procedure–II and completed additional research forms. Results The authors applied factor analysis to identify naturally occurring diagnostic groupings within the patient sample. The analysis yielded 10 clinically coherent personality diagnoses organized into three higher-order clusters: internalizing, externalizing, and borderline-dysregulated. The authors selected the most highly rated descriptors to construct a diagnostic prototype for each personality syndrome. In a second, independent sample, research interviewers and patients’ treating clinicians were able to diagnose the personality syndromes with high agreement and minimal comorbidity among diagnoses. Conclusions The empirically derived personality prototypes described here provide a framework for personality diagnosis that is both empirically based and clinically relevant. PMID:22193534

Anterior inferior plating versus superior plating for clavicle fracture: a meta-analysis.

PubMed

Ai, Jie; Kan, Shun-Li; Li, Hai-Liang; Xu, Hong; Liu, Yang; Ning, Guang-Zhi; Feng, Shi-Qing

2017-04-18

The position of plate fixation for clavicle fracture remains controversial. Our objective was to perform a comprehensive review of the literature and quantify the surgical parameters and clinical indexes between the anterior inferior plating and superior plating for clavicle fracture. PubMed, EMBASE, and the Cochrane Library were searched for randomized and non-randomized studies that compared the anterior inferior plating with the superior plating for clavicle fracture. The relative risk or standardized mean difference with 95% confidence interval was calculated using either a fixed- or random-effects model. Four randomized controlled trials and eight observational studies were identified to compare the surgical parameters and clinical indexes. For the surgical parameters, the anterior inferior plating group was better than the superior plating group in operation time and blood loss (P < 0.05). Furthermore, in terms of clinical indexes, the anterior inferior plating was superior to the superior plating in reducing the union time, and the two kinds of plate fixation methods were comparable in constant score, and the rate of infection, nonunion, and complications (P > 0.05). Based on the current evidence, the anterior inferior plating may reduce the blood loss, the operation and union time, but no differences were observed in constant score, and the rate of infection, nonunion, and complications between the two groups. Given that some of the studies have low quality, more randomized controlled trails with high quality should be conduct to further verify the findings.

Effectiveness of adjuvant radiotherapy in patients with oropharyngeal and floor of mouth squamous cell carcinoma and concomitant histological verification of singular ipsilateral cervical lymph node metastasis (pN1-state) - A prospective multicenter randomized controlled clinical trial using a comprehensive cohort design

PubMed Central

2009-01-01

Background Modern radiotherapy plays an important role in therapy of advanced head and neck carcinomas. However, no clinical studies have been published addressing the effectiveness of postoperative radiotherapy in patients with small tumor (pT1, pT2) and concomitant ipsilateral metastasis of a single lymph node (pN1), which would provide a basis for a general treatment recommendation. Methods/Design The present study is a non-blinded, prospective, multi-center randomized controlled trial (RCT). As the primary clinical endpoint, overall-survival in patients receiving postoperative radiation therapy vs. patients without adjuvant therapy following curative intended surgery is compared. The aim of the study is to enroll 560 adult males and females for 1:1 randomization to one of the two treatment arms (irradiation/no irradiation). Since patients with small tumor (T1/T2) but singular lymph node metastasis are rare and the amount of patients consenting to randomization is not predictable in advance, all patients rejecting randomization will be treated as preferred and enrolled in a prospective observational study (comprehensive cohort design) after giving informed consent. This observational part of the trial will be performed with maximum consistency to the treatment and observation protocol of the RCT. Because the impact of patient preference for a certain treatment option is not calculable, parallel design of RCT and observational study may provide a maximum of evidence and efficacy for evaluation of treatment outcome. Secondary clinical endpoints are as follows: incidence and time to tumor relapse (locoregional relapse, lymph node involvement and distant metastatic spread), Quality of life as reported by EORTC (QLQ-C30 with H&N 35 module), and time from operation to orofacial rehabilitation. All tumors represent a homogeneous clinical state and therefore additional investigation of protein expression levels within resection specimen may serve for establishment of surrogate parameters of patient outcome. Conclusion The inherent challenges of a rare clinical condition (pN1) and two substantially different therapy arms would limit the practicality of a classical randomized study. The concept of a Comprehensive Cohort Design combines the preference of a randomized study, with the option of careful data interpretation within an observational study. Trial registration ClinicalTrials.gov: NCT00964977 PMID:20028566

Interpreting “statistical hypothesis testing” results in clinical research

PubMed Central

Sarmukaddam, Sanjeev B.

2012-01-01

Difference between “Clinical Significance and Statistical Significance” should be kept in mind while interpreting “statistical hypothesis testing” results in clinical research. This fact is already known to many but again pointed out here as philosophy of “statistical hypothesis testing” is sometimes unnecessarily criticized mainly due to failure in considering such distinction. Randomized controlled trials are also wrongly criticized similarly. Some scientific method may not be applicable in some peculiar/particular situation does not mean that the method is useless. Also remember that “statistical hypothesis testing” is not for decision making and the field of “decision analysis” is very much an integral part of science of statistics. It is not correct to say that “confidence intervals have nothing to do with confidence” unless one understands meaning of the word “confidence” as used in context of confidence interval. Interpretation of the results of every study should always consider all possible alternative explanations like chance, bias, and confounding. Statistical tests in inferential statistics are, in general, designed to answer the question “How likely is the difference found in random sample(s) is due to chance” and therefore limitation of relying only on statistical significance in making clinical decisions should be avoided. PMID:22707861

Comparative effectiveness of instructional methods: oral and pharyngeal cancer examination.

PubMed

Clark, Nereyda P; Marks, John G; Sandow, Pamela R; Seleski, Christine E; Logan, Henrietta L

2014-04-01

This study compared the effectiveness of different methods of instruction for the oral and pharyngeal cancer examination. A group of thirty sophomore students at the University of Florida College of Dentistry were randomly assigned to three training groups: video instruction, a faculty-led hands-on instruction, or both video and hands-on instruction. The training intervention involved attending two sessions spaced two weeks apart. The first session used a pretest to assess students' baseline didactic knowledge and clinical examination technique. The second session utilized two posttests to assess the comparative effectiveness of the training methods on didactic knowledge and clinical technique. The key findings were that students performed the clinical examination significantly better with the combination of video and faculty-led hands-on instruction (p<0.01). All students improved their clinical exam skills, knowledge, and confidence in performing the oral and pharyngeal cancer examination independent of which training group they were assigned. Utilizing both video and interactive practice promoted greater performance of the clinical technique on the oral and pharyngeal cancer examination.

Forensic Luminol Blood Test for Preventing Cross-contamination in Dentistry: An Evaluation of a Dental School Clinic.

PubMed

Bortoluzzi, Marcelo Carlos; Cadore, Peterson; Gallon, Andrea; Imanishi, Soraia Almeida Watanabe

2014-10-01

More than 200 different diseases may be transmitted from exposure to blood in the dental setting. The aim of this study is to identify possible faults in the crosscontamination chain control in a dental school clinic searching for traces of blood in the clinical contact surfaces (CCS) through forensic luminol blood test. Traces of invisible blood where randomly searched in CCS of one dental school clinic. Forty eight surfaces areas in the CCS were tested and the presence of invisible and remnant blood was identified in 28 (58.3%) items. We suggest that the luminol method is suitable for identifying contamination with invisible blood traces and this method may be a useful tool to prevent cross-contamination in the dental care setting.

[Thinking on designation of sham acupuncture in clinical research].

PubMed

Pan, Li-Jia; Chen, Bo; Zhao, Xue; Guo, Yi

2014-01-01

Randomized controlled trials (RCT) is the source of the raw data of evidence-based medicine. Blind method is adopted in most of the high-quality RCT. Sham acupuncture is the main form of blinded in acupuncture clinical trial. In order to improve the quality of acupuncture clinical trail, based on the necessity of sham acupuncture in clinical research, the current situation as well as the existing problems of sham acupuncture, suggestions were put forward from the aspects of new way and new designation method which can be adopted as reference, and factors which have to be considered during the process of implementing. Various subjective and objective factors involving in the process of trial should be considered, and used of the current international standards, try to be quantification, and carry out strict quality monitoring.

Endovascular therapy for acute ischemic stroke.

PubMed

Broderick, Joseph P

2009-03-01

To review advances in endovascular therapy for acute ischemic stroke. Data from primate studies, randomized studies of intravenous recombinant tissue-type plasminogen activator, and nonrandomized and randomized studies of endovascular therapy were reviewed. Clinical trial data demonstrate the superiority of endovascular treatment with thrombolytic medication or mechanical methods to reopen arteries compared with control patients from the PROACT II Trial treated with heparin alone. However, these same clinical trials, as well as preclinical primate models, indicate that recanalization, whether by endovascular approaches or standard-dose recombinant tissue-type plasminogen activator, is unlikely to improve clinical outcome after a certain time point. Although the threshold beyond which reperfusion has no or little benefit has yet to be conclusively defined, accumulated data to this point indicate an overall threshold of approximately 6 to 7 hours. In addition, although the risk of symptomatic intracerebral hemorrhage is similar in trials of intravenous lytics and endovascular approaches, endovascular approaches have distinctive risk profiles that can impact outcome. The treatment of acute ischemic stroke is evolving with new tools to reopen arteries and salvage the ischemic brain. Ongoing randomized trials of these new approaches are prerequisite next steps to demonstrate whether reperfusion translates into clinical effectiveness. Physiologic time to reperfusion will remain critical no matter which tools prove most effective and safest.

The efficacy of low-level laser treatment in reducing pain and swelling after endodontic surgery: a systematic review

NASA Astrophysics Data System (ADS)

Moshari, Amirabbas; Vatanpour, Mehdi; Zakershahrak, Mehrsa

2016-03-01

Introduction: LLLT in oral cavity believed to reduce pain after endodontic surgery and wisdom tooth removal, to accelerate wound healing and to have an anti-inflammatory and regenerative effect. The aim of this systematic review therefore was to assess the proof available for the efficacy of low-level laser treatment in reducing pain and swelling after endodontic surgery. Methods: The PubMed service of the U.S. National Library of Medicine was searched with applicable search strategies. No language restriction was applied. The last electronic search was accomplished on August 31, 2015. All randomized clinical trials on the efficiency of low-level laser treatment in reducing pain and swelling after endodontic surgery was considered for the Meta-analysis. Quality consideration of the included randomized clinical trials was appraised according to CONSORT guidelines. Results: Only two randomized clinical trials were attained. These studies clarified that laser treatment could reduce pain and swelling, but the results were not significant. Conclusions: Low-level laser therapy can be advantageous for the reduction of postoperative pain but there is no strong confirmation for its efficiency. Its clinical utility and applicability relating to endodontic surgery, Along with the optimal energy dosage and the number of laser treatments needed after surgery, still, demand further research and experiment.

Randomized Controlled Trial of Antiseptic Hand Hygiene Methods in an Outpatient Surgery Clinic.

PubMed

Therattil, Paul J; Yueh, Janet H; Kordahi, Anthony M; Cherla, Deepa V; Lee, Edward S; Granick, Mark S

2015-12-01

Outpatient wound care plays an integral part in any plastic surgery practice. However, compliance with hand hygiene measures has shown to be low, due to skin irritation and lack of time. The objective of this trial was to determine whether single-use, long-acting antiseptics can be as effective as standard multiple-use hand hygiene methods in an outpatient surgical setting. A prospective, randomized controlled trial was performed in the authors' outpatient plastic surgery clinic at Rutgers New Jersey Medical School, Newark, NJ to compare the efficacy of an ethyl alcohol-based sanitizer (Avagard D Instant Hand Aniseptic, 3M Health Care, St. Paul, MN), a benzalkonium chloride-based sanitizer (Soft & Shield, Bioderm Technologies, Inc, Trenton, NJ, distributed by NAPP Technologies, Hackensack, NJ ), and soap and- water handwashing. Subjects included clinic personnel, who were followed throughout the course of a 3-hour clinic session with hourly hand bacterial counts taken. During the course of the trial, 95 subjects completed the clinic session utilizing 1 of the hand hygiene methods (36 ethyl alcohol-based sanitizer, 38 benzalkonium chloride-based sanitizer, and 21 soap-and-water handwashing). There was no difference between hand bacterial counts using the different methods at 4 hourly time points (P greater than 0.05). Hand bacterial counts increased significantly over the 3-hour clinic session with the ethyl alcohol-based sanitizer (9.24 to 21.90 CFU, P less than 0.05), benzalkonium chloride-based sanitizer (6.69 to 21.59 CFU, P less than 0.05), and soap-and-water handwashing (8.43 to 22.75 CFU, P less than 0.05). There does not appear to be any difference in efficacy between single-use, long-acting sanitizer, and standard multiple-use hand hygiene methods. Hand bacterial counts increased significantly over the course of the 3-hour clinic session regardless of the hand hygiene measure used. Hand condition of subjects was improved with the ethyl alcohol-based sanitizer and the benzalkonium chloride-based sanitizer compared with soap-and-water handwashing.

A combined pre-clinical meta-analysis and randomized confirmatory trial approach to improve data validity for therapeutic target validation.

PubMed

Kleikers, Pamela W M; Hooijmans, Carlijn; Göb, Eva; Langhauser, Friederike; Rewell, Sarah S J; Radermacher, Kim; Ritskes-Hoitinga, Merel; Howells, David W; Kleinschnitz, Christoph; Schmidt, Harald H H W

2015-08-27

Biomedical research suffers from a dramatically poor translational success. For example, in ischemic stroke, a condition with a high medical need, over a thousand experimental drug targets were unsuccessful. Here, we adopt methods from clinical research for a late-stage pre-clinical meta-analysis (MA) and randomized confirmatory trial (pRCT) approach. A profound body of literature suggests NOX2 to be a major therapeutic target in stroke. Systematic review and MA of all available NOX2(-/y) studies revealed a positive publication bias and lack of statistical power to detect a relevant reduction in infarct size. A fully powered multi-center pRCT rejects NOX2 as a target to improve neurofunctional outcomes or achieve a translationally relevant infarct size reduction. Thus stringent statistical thresholds, reporting negative data and a MA-pRCT approach can ensure biomedical data validity and overcome risks of bias.

Strategies for dealing with missing data in clinical trials: from design to analysis.

PubMed

Dziura, James D; Post, Lori A; Zhao, Qing; Fu, Zhixuan; Peduzzi, Peter

2013-09-01

Randomized clinical trials are the gold standard for evaluating interventions as randomized assignment equalizes known and unknown characteristics between intervention groups. However, when participants miss visits, the ability to conduct an intent-to-treat analysis and draw conclusions about a causal link is compromised. As guidance to those performing clinical trials, this review is a non-technical overview of the consequences of missing data and a prescription for its treatment beyond the typical analytic approaches to the entire research process. Examples of bias from incorrect analysis with missing data and discussion of the advantages/disadvantages of analytic methods are given. As no single analysis is definitive when missing data occurs, strategies for its prevention throughout the course of a trial are presented. We aim to convey an appreciation for how missing data influences results and an understanding of the need for careful consideration of missing data during the design, planning, conduct, and analytic stages.

Homeopathic treatment of minor aphthous ulcer: a randomized, placebo-controlled clinical trial.

PubMed

Mousavi, Fahimeh; Mojaver, Yalda Nozad; Asadzadeh, Mehdi; Mirzazadeh, Mustafa

2009-07-01

The objectives of this study were to clinically determine the efficacy of individualised homeopathy in the treatment of minor recurrent aphthous ulceration (MiRAU). A randomized, single blind, placebo-controlled clinical trial of individualised homeopathy. One hundred patients with minor aphthous ulcer were treated with individualised homeopathic medicines or placebo and followed up for 6 days. Patients received two doses of individualised homeopathic medicines in the 6C potency as oral liquid at baseline and 12 h later. Pain intensity and ulcer size were recorded at baseline during and at the end of the trial (mornings of days 4 and 6). All 100 patients completed treatment. Between group differences for pain intensity and ulcer size were statistically significant at day 4 and at day 6 (P<0.05). No adverse effects were reported. The results suggest that homeopathic treatment is an effective and safe method in the treatment of MiRAU.

[Critical of the additive model of the randomized controlled trial].

PubMed

Boussageon, Rémy; Gueyffier, François; Bejan-Angoulvant, Theodora; Felden-Dominiak, Géraldine

2008-01-01

Randomized, double-blind, placebo-controlled clinical trials are currently the best way to demonstrate the clinical effectiveness of drugs. Its methodology relies on the method of difference (John Stuart Mill), through which the observed difference between two groups (drug vs placebo) can be attributed to the pharmacological effect of the drug being tested. However, this additive model can be questioned in the event of statistical interactions between the pharmacological and the placebo effects. Evidence in different domains has shown that the placebo effect can influence the effect of the active principle. This article evaluates the methodological, clinical and epistemological consequences of this phenomenon. Topics treated include extrapolating results, accounting for heterogeneous results, demonstrating the existence of several factors in the placebo effect, the necessity to take these factors into account for given symptoms or pathologies, as well as the problem of the "specific" effect.

Video- or text-based e-learning when teaching clinical procedures? A randomized controlled trial

PubMed Central

Buch, Steen Vigh; Treschow, Frederik Philip; Svendsen, Jesper Brink; Worm, Bjarne Skjødt

2014-01-01

Background and aims This study investigated the effectiveness of two different levels of e-learning when teaching clinical skills to medical students. Materials and methods Sixty medical students were included and randomized into two comparable groups. The groups were given either a video- or text/picture-based e-learning module and subsequently underwent both theoretical and practical examination. A follow-up test was performed 1 month later. Results The students in the video group performed better than the illustrated text-based group in the practical examination, both in the primary test (P<0.001) and in the follow-up test (P<0.01). Regarding theoretical knowledge, no differences were found between the groups on the primary test, though the video group performed better on the follow-up test (P=0.04). Conclusion Video-based e-learning is superior to illustrated text-based e-learning when teaching certain practical clinical skills. PMID:25152638

Comparison of the effect of web-based, simulation-based, and conventional training on the accuracy of visual estimation of postpartum hemorrhage volume on midwifery students: A randomized clinical trial

PubMed Central

Kordi, Masoumeh; Fakari, Farzaneh Rashidi; Mazloum, Seyed Reza; Khadivzadeh, Talaat; Akhlaghi, Farideh; Tara, Mahmoud

2016-01-01

Introduction: Delay in diagnosis of bleeding can be due to underestimation of the actual amount of blood loss during delivery. Therefore, this research aimed to compare the efficacy of web-based, simulation-based, and conventional training on the accuracy of visual estimation of postpartum hemorrhage volume. Materials and Methods: This three-group randomized clinical trial study was performed on 105 midwifery students in Mashhad School of Nursing and Midwifery in 2013. The samples were selected by the convenience method and were randomly divided into three groups of web-based, simulation-based, and conventional training. The three groups participated before and 1 week after the training course in eight station practical tests, then, the students of the web-based group were trained on-line for 1 week, the students of the simulation-based group were trained in the Clinical Skills Centre for 4 h, and the students of the conventional group were trained for 4 h presentation by researchers. The data gathering tool was a demographic questionnaire designed by the researchers and objective structured clinical examination. Data were analyzed by software version 11.5. Results: The accuracy of visual estimation of postpartum hemorrhage volume after training increased significantly in the three groups at all stations (1, 2, 4, 5, 6 and 7 (P = 0.001), 8 (P = 0.027)) except station 3 (blood loss of 20 cc, P = 0.095), but the mean score of blood loss estimation after training did not significantly different between the three groups (P = 0.95). Conclusion: Training increased the accuracy of estimation of postpartum hemorrhage, but no significant difference was found among the three training groups. We can use web-based training as a substitute or supplement of training along with two other more common simulation and conventional methods. PMID:27500175

Adjusted Clinical Groups: Predictive Accuracy for Medicaid Enrollees in Three States

PubMed Central

Adams, E. Kathleen; Bronstein, Janet M.; Raskind-Hood, Cheryl

2002-01-01

Actuarial split-sample methods were used to assess predictive accuracy of adjusted clinical groups (ACGs) for Medicaid enrollees in Georgia, Mississippi (lagging in managed care penetration), and California. Accuracy for two non-random groups—high-cost and located in urban poor areas—was assessed. Measures for random groups were derived with and without short-term enrollees to assess the effect of turnover on predictive accuracy. ACGs improved predictive accuracy for high-cost conditions in all States, but did so only for those in Georgia's poorest urban areas. Higher and more unpredictable expenses of short-term enrollees moderated the predictive power of ACGs. This limitation was significant in Mississippi due in part, to that State's very high proportion of short-term enrollees. PMID:12545598

Inference in randomized trials with death and missingness.

PubMed

Wang, Chenguang; Scharfstein, Daniel O; Colantuoni, Elizabeth; Girard, Timothy D; Yan, Ying

2017-06-01

In randomized studies involving severely ill patients, functional outcomes are often unobserved due to missed clinic visits, premature withdrawal, or death. It is well known that if these unobserved functional outcomes are not handled properly, biased treatment comparisons can be produced. In this article, we propose a procedure for comparing treatments that is based on a composite endpoint that combines information on both the functional outcome and survival. We further propose a missing data imputation scheme and sensitivity analysis strategy to handle the unobserved functional outcomes not due to death. Illustrations of the proposed method are given by analyzing data from a recent non-small cell lung cancer clinical trial and a recent trial of sedation interruption among mechanically ventilated patients. © 2016, The International Biometric Society.

Recruitment strategies in two reproductive medicine network infertility trials.

PubMed

Usadi, Rebecca S; Diamond, Michael P; Legro, Richard S; Schlaff, William D; Hansen, Karl R; Casson, Peter; Christman, Gregory; Wright Bates, G; Baker, Valerie; Seungdamrong, Aimee; Rosen, Mitchell P; Lucidi, Scott; Thomas, Tracey; Huang, Hao; Santoro, Nanette; Eisenberg, Esther; Zhang, Heping; Alvero, Ruben

2015-11-01

Recruitment of individuals into clinical trials is a critical step in completing studies. Reports examining the effectiveness of different recruitment strategies, and specifically in infertile couples, are limited. We investigated recruitment methods used in two NIH sponsored trials, Pregnancy in Polycystic Ovary Syndrome (PPCOS II) and Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS), and examined which strategies yielded the greatest number of participants completing the trials. 3683 couples were eligible for screening. 1650 participants were randomized and 1339 completed the trials. 750 women were randomized in PPCOS II; 212 of the participants who completed the trial were referred by physicians. Participants recruited from radio ads (84/750) and the internet (81/750) resulted in similar rates of trial completion in PPCOS II. 900 participants were randomized in AMIGOS. 440 participants who completed the trial were referred to the study by physicians. The next most successful method in AMIGOS was the use of the internet, achieving 78 completed participants. Radio ads proved the most successful strategy in both trials for participants who earned <$50,000 annually. Radio ads were most successful in enrolling white patients in PPCOS II and black patients in AMIGOS. Seven ancillary Clinical Research Scientist Training (CREST) sites enrolled 324 of the participants who completed the trials. Physician referral was the most successful recruitment strategy. Radio ads and the internet were the next most successful strategies, particularly for women of limited income. Ancillary clinical sites were important for overall recruitment. Copyright © 2015 Elsevier Inc. All rights reserved.

The clinical and cost-effectiveness of the BRinging Information and Guided Help Together (BRIGHT) intervention for the self-management support of people with stage 3 chronic kidney disease in primary care: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Improving the quality of care for people with vascular disease is a key priority. Chronic kidney disease (CKD) has recently been included as a target condition for general practices to add to registers of chronic conditions as part of the Quality and Outcome Framework. This paper outlines the implementation and evaluation of a self-management intervention involving an information guidebook, tailored access to local resources and telephone support for people with stage 3 chronic kidney disease. Methods/Design The study involves a multi-site, longitudinal patient-level randomized controlled trial. The study will evaluate the clinical use and cost-effectiveness of a complex self-management intervention for people with stage 3 chronic kidney disease in terms of self-management capacity, health-related quality of life and blood pressure control compared to care as usual. We describe the methods of the patient-level randomized controlled trial. Discussion The management of chronic kidney disease is a developing area of research. The BRinging Information and Guided Help Together (BRIGHT) trial aims to provide evidence that a complementary package of support for people with vascular disease that targets both clinical and social need broadens the opportunities of self-management support by addressing problems related to social disadvantage. Trial registration Trial registration reference: ISRCTN45433299 PMID:23356861

Microbiological and clinical effects of probiotics and antibiotics on nonsurgical treatment of chronic periodontitis: a randomized placebo- controlled trial with 9-month follow-up

PubMed Central

Morales, Alicia; Gandolfo, Alessandro; Bravo, Joel; Carvajal, Paola; Silva, Nora; Godoy, Claudia; Garcia-Sesnich, Jocelyn; Hoare, Anilei; Diaz, Patricia; Gamonal, Jorge

2018-01-01

ABSTRACT Objective The aim of this double-blind, placebo-controlled and parallel- arm randomized clinical trial was to evaluate the effects of Lactobacillus rhamnosus SP1-containing probiotic sachet and azithromycin tablets as an adjunct to nonsurgical therapy in clinical parameters and in presence and levels of Tannerella forsythia, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Material and Methods Forty-seven systemically healthy volunteers with chronic periodontitis were recruited and monitored clinically and microbiologically at baseline for 3, 6 and 9 months after therapy. Subgingival plaque samples were collected from four periodontal sites with clinical attachment level ≥1 mm, probing pocket depth ≥4 mm and bleeding on probing, one site in each quadrant. Samples were cultivated and processed using the PCR technique. Patients received nonsurgical therapy including scaling and root planing (SRP) and were randomly assigned to a probiotic (n=16), antibiotic (n = 16) or placebo (n = 15) group. L. rhamnosus SP1 was taken once a day for 3 months. Azithromycin 500mg was taken once a day for 5 days. Results All groups showed improvements in clinical and microbiological parameters at all time points evaluated. Probiotic and antibiotic groups showed greater reductions in cultivable microbiota compared with baseline. The placebo group showed greater reduction in number of subjects with P. gingivalis compared with baseline. However, there were no significant differences between groups. Conclusions The adjunctive use of L. rhamnosus SP1 sachets and azithromycin during initial therapy resulted in similar clinical and microbiological improvements compared with the placebo group. PMID:29364340

Perceptions of Radiation Oncologists and Urologists on Sources and Type of Evidence to Inform Prostate Cancer Treatment Decisions

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

Han, Leona C.; Delpe, Sophia; Shah, Nilay D.

2014-06-01

Purpose: To perform a national survey of radiation oncologists and urologists about the type of resources used and the level of evidence needed to change clinical practice in localized prostate cancer. Methods and Materials: From a random sample, 1422 physicians were mailed a survey assessing the types of information used and what level of evidence could alter their clinical practice in prostate cancer. Multivariable logistic regression models were used to identify differences in physician characteristics for each outcome. Results: Survey response rates were similar for radiation oncologists and urologists (44% vs 46%; P=.46). Specialty-specific journals represented the most commonly usedmore » resource for informing the clinical practice for radiation oncologists (65%) and urologists (70%). Relative to radiation oncologists, urologists were less likely to report utilizing top-tier medical journals (25% vs 39%; adjusted odds ratio [OR] 0.50; P=.01) or cancer journals (22% vs 51%; adjusted OR 0.50; P<.001) but more likely to rely on clinical guidelines (46% vs 38%; adjusted OR 1.6; P=.006). Both radiation oncologists and urologists most commonly reported large randomized, clinical trials as the level of evidence to change treatment recommendations for localized prostate cancer (85% vs 77%; P=.009). Conclusions: Both specialties rely on their own specialty-specific journals and view randomized, clinical trials as the level of evidence needed to change clinical practice. Our study provides a context on meaningful ways of disseminating evidence for localized prostate cancer.« less

Bridging the clinician/researcher gap with systemic research: the case for process research, dyadic, and sequential analysis.

PubMed

Oka, Megan; Whiting, Jason

2013-01-01

In Marriage and Family Therapy (MFT), as in many clinical disciplines, concern surfaces about the clinician/researcher gap. This gap includes a lack of accessible, practical research for clinicians. MFT clinical research often borrows from the medical tradition of randomized control trials, which typically use linear methods, or follow procedures distanced from "real-world" therapy. We review traditional research methods and their use in MFT and propose increased use of methods that are more systemic in nature and more applicable to MFTs: process research, dyadic data analysis, and sequential analysis. We will review current research employing these methods, as well as suggestions and directions for further research. © 2013 American Association for Marriage and Family Therapy.

Short term treatment versus long term management of neck and back disability in older adults utilizing spinal manipulative therapy and supervised exercise: a parallel-group randomized clinical trial evaluating relative effectiveness and harms

PubMed Central

2014-01-01

Background Back and neck disability are frequent in older adults resulting in loss of function and independence. Exercise therapy and manual therapy, like spinal manipulative therapy (SMT), have evidence of short and intermediate term effectiveness for spinal disability in the general population and growing evidence in older adults. For older populations experiencing chronic spinal conditions, long term management may be more appropriate to maintain improvement and minimize the impact of future exacerbations. Research is limited comparing short courses of treatment to long term management of spinal disability. The primary aim is to compare the relative effectiveness of 12 weeks versus 36 weeks of SMT and supervised rehabilitative exercise (SRE) in older adults with back and neck disability. Methods/Design Randomized, mixed-methods, comparative effectiveness trial conducted at a university-affiliated research clinic in the Minneapolis/St. Paul, Minnesota metropolitan area. Participants Independently ambulatory community dwelling adults ≥ 65 years of age with back and neck disability of minimum 12 weeks duration (n = 200). Interventions 12 weeks SMT + SRE or 36 weeks SMT + SRE. Randomization Blocked 1:1 allocation; computer generated scheme, concealed in sequentially numbered, opaque, sealed envelopes. Blinding Functional outcome examiners are blinded to treatment allocation; physical nature of the treatments prevents blinding of participants and providers to treatment assignment. Primary endpoint 36 weeks post-randomization. Data collection Self-report questionnaires administered at 2 baseline visits and 4, 12, 24, 36, 52, and 78 weeks post-randomization. Primary outcomes include back and neck disability, measured by the Oswestry Disability Index and Neck Disability Index. Secondary outcomes include pain, general health status, improvement, self-efficacy, kinesiophobia, satisfaction, and medication use. Functional outcome assessment occurs at baseline and week 37 for hand grip strength, short physical performance battery, and accelerometry. Individual qualitative interviews are conducted when treatment ends. Data on expectations, falls, side effects, and adverse events are systematically collected. Primary analysis Linear mixed-model method for repeated measures to test for between-group differences with baseline values as covariates. Discussion Treatments that address the management of spinal disability in older adults may have far reaching implications for patient outcomes, clinical guidelines, and healthcare policy. Trial registry www.ClinicalTrials.gov; Identifier: NCT01057706. PMID:25478141

Non-surgical treatment of hip osteoarthritis. Hip school, with or without the addition of manual therapy, in comparison to a minimal control intervention: Protocol for a three-armed randomized clinical trial

PubMed Central

2011-01-01

Background Hip osteoarthritis is a common and chronic condition resulting in pain, functional disability and reduced quality of life. In the early stages of the disease, a combination of non-pharmacological and pharmacological treatment is recommended. There is evidence from several trials that exercise therapy is effective. In addition, single trials suggest that patient education in the form of a hip school is a promising intervention and that manual therapy is superior to exercise. Methods/Design This is a randomized clinical trial. Patients with clinical and radiological hip osteoarthritis, 40-80 years of age, and without indication for hip surgery were randomized into 3 groups. The active intervention groups A and B received six weeks of hip school, taught by a physiotherapist, for a total of 5 sessions. In addition, group B received manual therapy consisting of joint manipulation and soft-tissue therapy twice a week for six weeks. Group C received a self-care information leaflet containing advice on "live as usual" and stretching exercises from the hip school. The primary time point for assessing relative effectiveness is at the end of the six weeks intervention period with follow-ups after three and 12 months. Primary outcome measure is pain measured on an eleven-point numeric rating scale. Secondary outcome measures are the hip dysfunction and osteoarthritis outcome score, patient's global perceived effect, patient specific functional scale, general quality of life and hip range of motion. Discussion To our knowledge this is the first randomized clinical trial comparing a patient education program with or without the addition of manual therapy to a minimal intervention for patients with hip osteoarthritis. Trial registration ClinicalTrials NCT01039337 PMID:21542914

Teleconferenced Educational Detailing: Diabetes Education for Primary Care Physicians

ERIC Educational Resources Information Center

Harris, Stewart B.; Leiter, Lawrence A.; Webster-Bogaert, Susan; Van, Daphne M.; O'Neill, Colleen

2005-01-01

Introduction: Formal didactic continuing medical education (CME) is relatively ineffective for changing physician behavior. Diabetes mellitus is an increasingly prevalent disease, and interventions to improve adherence to clinical practice guidelines (CPGs) are needed. Methods: A stratified, cluster-randomized, controlled trial design was used to…

Comparison between Unilateral and Bilateral Ovarian Drilling in Clomiphene Citrate Resistance Polycystic Ovary Syndrome Patients: A Randomized Clinical Trial of Efficacy

PubMed Central

Zahiri Sorouri, Ziba; Sharami, Seyede Hajar; Tahersima, Zinab; Salamat, Fatemeh

2015-01-01

Background Laparoscopic ovarian drilling (LOD) is an alternative method to induce ovulation in polycystic ovary syndrome (PCOS) patients with clomiphene citrate (CC) resistant instead of gonadotropins. This study aimed to compare the efficacy of unilateral LOD (ULOD) versus bilateral LOD (BLOD) in CC resistance PCOS patients in terms of ovulation and pregnancy rates. Materials and Methods In a prospective randomized clinical trial study, we included 100 PCOS patients with CC resistance attending to Al-Zahra Hospital in Rasht, Guilan Province, Iran, from June 2011 to July 2012. Patients were randomly divided into two ULOD and BLOD groups with equal numbers. The clinical and biochemical responses on ovulation and pregnancy rates were assessed over a 6-month follow-up period. Results Differences in baseline characteristics of patients between two groups prior to laparoscopy were not significant (p>0.05). There were no significant differences between the two groups in terms of clinical and biochemical responses, spontaneous menstruation (66.1 vs. 71.1%), spontaneous ovulation rate (60 vs. 64.4%), and pregnancy rate (33.1 vs. 40%) (p>0.05). Following drilling, there was a significant decrease in mean serum concentrations of luteinizing hormone (LH) (p=0.001) and testosterone (p=0.001) in both the groups. Mean decrease in serum LH (p=0.322) and testosterone concentrations (p=0.079) were not statistically significant between two groups. Mean serum level of follicle stimulating hormone (FSH) did not change significantly in two groups after LOD (p>0.05). Conclusion Based on results of this study, ULOD seems to be equally efficacious as BLOD in terms of ovulation and pregnancy rates (Registration Number: IRCT138903291306N2). PMID:25918587

Telephone Cognitive-Behavioral Therapy for Adolescents With Obsessive-Compulsive Disorder: A Randomized Controlled Non-inferiority Trial

PubMed Central

Turner, Cynthia M.; Mataix-Cols, David; Lovell, Karina; Krebs, Georgina; Lang, Katie; Byford, Sarah; Heyman, Isobel

2014-01-01

Objective Many adolescents with obsessive-compulsive disorder (OCD) do not have access to evidence-based treatment. A randomized controlled non-inferiority trial was conducted in a specialist OCD clinic to evaluate the effectiveness of telephone cognitive-behavioral therapy (TCBT) for adolescents with OCD compared to standard clinic-based, face-to-face CBT. Method Seventy-two adolescents, aged 11 through 18 years with primary OCD, and their parents were randomized to receive specialist TCBT or CBT. The intervention provided differed only in the method of treatment delivery. All participants received up to 14 sessions of CBT, incorporating exposure with response prevention (E/RP), provided by experienced therapists. The primary outcome measure was the Children’s Yale–Brown Obsessive-Compulsive Scale (CY-BOCS). Blind assessor ratings were obtained at midtreatment, posttreatment, 3-month, 6-month, and 12-month follow-up. Results Intent-to-treat analyses indicated that TCBT was not inferior to face-to-face CBT at posttreatment, 3-month, and 6-month follow-up. At 12-month follow-up, there were no significant between-group differences on the CY-BOCS, but the confidence intervals exceeded the non-inferiority threshold. All secondary measures confirmed non-inferiority at all assessment points. Improvements made during treatment were maintained through to 12-month follow-up. Participants in each condition reported high levels of satisfaction with the intervention received. Conclusion TCBT is an effective treatment and is not inferior to standard clinic-based CBT, at least in the midterm. This approach provides a means of making a specialized treatment more accessible to many adolescents with OCD. Clinical trial registration information–Evaluation of telephone-administered cognitive-behaviour therapy (CBT) for young people with obsessive-compulsive disorder (OCD); http://www.controlled-trials.com; ISRCTN27070832. PMID:25457928

Patient Satisfaction with Different Interpreting Methods: A Randomized Controlled Trial

PubMed Central

Leng, Jennifer; Shapiro, Ephraim; Abramson, David; Motola, Ivette; Shield, David C.; Changrani, Jyotsna

2007-01-01

Background Growth of the foreign-born population in the U.S. has led to increasing numbers of limited-English-proficient (LEP) patients. Innovative medical interpreting strategies, including remote simultaneous medical interpreting (RSMI), have arisen to address the language barrier. This study evaluates the impact of interpreting method on patient satisfaction. Methods 1,276 English-, Spanish-, Mandarin-, and Cantonese-speaking patients attending the primary care clinic and emergency department of a large New York City municipal hospital were screened for enrollment in a randomized controlled trial. Language-discordant patients were randomized to RSMI or usual and customary (U&C) interpreting. Patients with language-concordant providers received usual care. Demographic and patient satisfaction questionnaires were administered to all participants. Results 541 patients were language-concordant with their providers and not randomized; 371 were randomized to RSMI, 167 of whom were exposed to RSMI; and 364 were randomized to U&C, 198 of whom were exposed to U&C. Patients randomized to RSMI were more likely than those with U&C to think doctors treated them with respect (RSMI 71%, U&C 64%, p < 0.05), but they did not differ in other measures of physician communication/care. In a linear regression analysis, exposure to RSMI was significantly associated with an increase in overall satisfaction with physician communication/care (β 0.10, 95% CI 0.02–0.18, scale 0–1.0). Patients randomized to RSMI were more likely to think the interpreting method protected their privacy (RSMI 51%, U&C 38%, p < 0.05). Patients randomized to either arm of interpretation reported less comprehension and satisfaction than patients in language-concordant encounters. Conclusions While not a substitute for language-concordant providers, RSMI can improve patient satisfaction and privacy among LEP patients. Implementing RSMI should be considered an important component of a multipronged approach to addressing language barriers in health care. PMID:17957417

A web-based screening and accrual strategy for a cancer prevention clinical trial in healthy smokers.

PubMed

Mohebati, Arash; Knutson, Allison; Zhou, Xi Kathy; Smith, Judith J; Brown, Powel H; Dannenberg, Andrew J; Szabo, Eva

2012-09-01

Screening and recruitment of qualified subjects for clinical trials is an essential component of translational research, and it can be quite challenging if the most efficient recruitment method is not utilized. In this report, we describe a successful web-based screening and accrual method used in a randomized prospective chemoprevention clinical trial with urinary biomarker endpoints. The targeted study population was a group of at-risk healthy current smokers with no evidence of lung disease. Craigslist was used as the sole recruitment modality for this study. All interested subjects were directed to a pre-screening website, in which subject questionnaire responses were linked to the study coordinator's secure e-mail account. Of the 429 initial inquiries, 189 individuals were initially eligible based on the questionnaire response. One hundred twenty-two people were telephone-screened, of whom 98 subjects were consented, 84 were randomized and 77 subjects completed the study successfully. Utilizing this single web-based advertising strategy, accrual for the trial was completed 7 months prior to the projected date. Craigslist is a cost effective and efficient web-based resource that can be utilized in accruing subjects to some chemoprevention trials. Published by Elsevier Inc.

A web-based screening and accrual strategy for a cancer prevention clinical trial in healthy smokers

PubMed Central

Mohebati, Arash; Knutson, Allison; Zhou, Xi Kathy; Smith, Judith J.; Brown, Powel H.; Dannenberg, Andrew J.; Szabo, Eva

2012-01-01

Screening and recruitment of qualified subjects for clinical trials is an essential component of translational research, and it can be quite challenging if the most efficient recruitment method is not utilized. In this report, we describe a successful web-based screening and accrual method used in a randomized prospective chemoprevention clinical trial with urinary biomarker endpoints. The targeted study population was a group of at-risk healthy current smokers with no evidence of lung disease. Craigslist was used as the sole recruitment modality for this study. All interested subjects were directed to a pre-screening website, in which subject questionnaire responses were linked to the study coordinator's secure e-mail account. Of the 429 initial inquiries, 189 individuals were initially eligible based on the questionnaire response. One hundred twenty-two people were telephone-screened, of whom 98 subjects were consented, 84 were randomized and 77 subjects completed the study successfully. Utilizing this single web-based advertising strategy, accrual for the trial was completed 7 months prior to the projected date. Craigslist is a cost effective and efficient web-based resource that can be utilized in accruing subjects to some chemoprevention trials. PMID:22771576

Recruitment of young adults into a randomized controlled trial of weight gain prevention: message development, methods, and cost.

PubMed

Tate, Deborah F; LaRose, Jessica G; Griffin, Leah P; Erickson, Karen E; Robichaud, Erica F; Perdue, Letitia; Espeland, Mark A; Wing, Rena R

2014-08-16

Young adulthood (age 18 to 35) is a high-risk period for unhealthy weight gain. Few studies have recruited for prevention of weight gain, particularly in young adults. This paper describes the recruitment protocol used in the Study of Novel Approaches to Prevention (SNAP). We conducted extensive formative work to inform recruitment methods and message development. We worked with a professional marketing firm to synthesize major themes and subsequently develop age-appropriate messages for recruitment. A variety of approaches and channels were used across two clinical centers to recruit young adults who were normal or overweight (body mass index (BMI) 21 to 30 kg/m2) for a 3-year intervention designed to prevent weight gain. We tracked recruitment methods, yields, and costs by method. Logistic regression was used to identify recruitment methods that had the highest relative yield for subgroups of interest with covariate adjustments for clinic. The final sample of 599 participants (27% minority, 22% male) was recruited over a 19-month period of sustained efforts. About 10% of those who initially expressed interest via a screening website were randomized. The most common reason for ineligibility was already being obese (BMI >30 kg/m2). The top two methods for recruitment were mass mailing followed by email; together they were cited by 62% of those recruited. Television, radio, paid print advertising, flyers and community events each yielded fewer than 10% of study participants. Email was the most cost-effective method per study participant recruited. These findings can guide future efforts to recruit young adults and for trials targeting weight gain prevention. ClinicalTrials.gov NCT01183689 (registered 13 August 2010).

Characterizing and Managing Missing Structured Data in Electronic Health Records: Data Analysis.

PubMed

Beaulieu-Jones, Brett K; Lavage, Daniel R; Snyder, John W; Moore, Jason H; Pendergrass, Sarah A; Bauer, Christopher R

2018-02-23

Missing data is a challenge for all studies; however, this is especially true for electronic health record (EHR)-based analyses. Failure to appropriately consider missing data can lead to biased results. While there has been extensive theoretical work on imputation, and many sophisticated methods are now available, it remains quite challenging for researchers to implement these methods appropriately. Here, we provide detailed procedures for when and how to conduct imputation of EHR laboratory results. The objective of this study was to demonstrate how the mechanism of missingness can be assessed, evaluate the performance of a variety of imputation methods, and describe some of the most frequent problems that can be encountered. We analyzed clinical laboratory measures from 602,366 patients in the EHR of Geisinger Health System in Pennsylvania, USA. Using these data, we constructed a representative set of complete cases and assessed the performance of 12 different imputation methods for missing data that was simulated based on 4 mechanisms of missingness (missing completely at random, missing not at random, missing at random, and real data modelling). Our results showed that several methods, including variations of Multivariate Imputation by Chained Equations (MICE) and softImpute, consistently imputed missing values with low error; however, only a subset of the MICE methods was suitable for multiple imputation. The analyses we describe provide an outline of considerations for dealing with missing EHR data, steps that researchers can perform to characterize missingness within their own data, and an evaluation of methods that can be applied to impute clinical data. While the performance of methods may vary between datasets, the process we describe can be generalized to the majority of structured data types that exist in EHRs, and all of our methods and code are publicly available. ©Brett K Beaulieu-Jones, Daniel R Lavage, John W Snyder, Jason H Moore, Sarah A Pendergrass, Christopher R Bauer. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 23.02.2018.

Randomized clinical trials and observational studies in the assessment of drug safety.

PubMed

Sawchik, J; Hamdani, J; Vanhaeverbeek, M

2018-05-01

Randomized clinical trials are considered as the preferred design to assess the potential causal relationships between drugs or other medical interventions and intended effects. For this reason, randomized clinical trials are generally the basis of development programs in the life cycle of drugs and the cornerstone of evidence-based medicine. Instead, randomized clinical trials are not the design of choice for the detection and assessment of rare, delayed and/or unexpected effects related to drug safety. Moreover, the highly homogeneous populations resulting from restrictive eligibility criteria make randomized clinical trials inappropriate to describe comprehensively the safety profile of drugs. In that context, observational studies have a key added value when evaluating the benefit-risk balance of the drugs. However, observational studies are more prone to bias than randomized clinical trials and they have to be designed, conducted and reported judiciously. In this article, we discuss the strengths and limitations of randomized clinical trials and of observational studies, more particularly regarding their contribution to the knowledge of medicines' safety profile. In addition, we present general recommendations for the sensible use of observational data. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Study Comparing Vein Integrity and Clinical Outcomes in Open Vein Harvesting and 2 Types of Endoscopic Vein Harvesting for Coronary Artery Bypass Grafting: The VICO Randomized Clinical Trial (Vein Integrity and Clinical Outcomes)

PubMed Central

Krishnamoorthy, Bhuvaneswari; Critchley, William R.; Thompson, Alexander J.; Payne, Katherine; Morris, Julie; Venkateswaran, Rajamiyer V.; Caress, Ann L.

2018-01-01

Background Current consensus statements maintain that endoscopic vein harvesting (EVH) should be standard care in coronary artery bypass graft surgery, but vein quality and clinical outcomes have been questioned. The VICO trial (Vein Integrity and Clinical Outcomes) was designed to assess the impact of different vein harvesting methods on vessel damage and whether this contributes to clinical outcomes after coronary artery bypass grafting. Methods In this single-center, randomized clinical trial, patients undergoing coronary artery bypass grafting with an internal mammary artery and with 1 to 4 vein grafts were recruited. All veins were harvested by a single experienced practitioner. We randomly allocated 300 patients into closed tunnel CO2 EVH (n=100), open tunnel CO2 EVH (n=100), and traditional open vein harvesting (n=100) groups. The primary end point was endothelial integrity and muscular damage of the harvested vein. Secondary end points included clinical outcomes (major adverse cardiac events), use of healthcare resources, and impact on health status (quality-adjusted life-years). Results The open vein harvesting group demonstrated marginally better endothelial integrity in random samples (85% versus 88% versus 93% for closed tunnel EVH, open tunnel EVH, and open vein harvesting; P<0.001). Closed tunnel EVH displayed the lowest longitudinal hypertrophy (1% versus 13.5% versus 3%; P=0.001). However, no differences in endothelial stretching were observed between groups (37% versus 37% versus 31%; P=0.62). Secondary clinical outcomes demonstrated no significant differences in composite major adverse cardiac event scores at each time point up to 48 months. The quality-adjusted life-year gain per patient was 0.11 (P<0.001) for closed tunnel EVH and 0.07 (P=0.003) for open tunnel EVH compared with open vein harvesting. The likelihood of being cost-effective, at a predefined threshold of £20 000 per quality-adjusted life-year gained, was 75% for closed tunnel EVH, 19% for open tunnel EVH, and 6% for open vein harvesting. Conclusions Our study demonstrates that harvesting techniques affect the integrity of different vein layers, albeit only slightly. Secondary outcomes suggest that histological findings do not directly contribute to major adverse cardiac event outcomes. Gains in health status were observed, and cost-effectiveness was better with closed tunnel EVH. High-level experience with endoscopic harvesting performed by a dedicated specialist practitioner gives optimal results comparable to those of open vein harvesting. Clinical Trial Registration URL: https://www.isrctn.com. International Standard Randomised Controlled Trial Registry Number: 91485426. PMID:28637880

Family-based treatment of a 17-year-old twin presenting with emerging anorexia nervosa: a case study using the "Maudsley method".

PubMed

Loeb, Katharine L; Hirsch, Alicia M; Greif, Rebecca; Hildebrandt, Thomas B

2009-01-01

This article describes the successful application of family-based treatment (FBT) for a 17-year-old identical twin presenting with a 4-month history of clinically significant symptoms of anorexia nervosa (AN). FBT is a manualized treatment that has been studied in randomized controlled trials for adolescents with AN. This case study illustrates the administration of this evidence-based intervention in a clinical setting, highlighting how the best available research was used to make clinical decisions at each stage of treatment delivery.

Effectiveness of 3 methods of anchorage reinforcement for maximum anchorage in adolescents: A 3-arm multicenter randomized clinical trial.

PubMed

Sandler, Jonathan; Murray, Alison; Thiruvenkatachari, Badri; Gutierrez, Rodrigo; Speight, Paul; O'Brien, Kevin

2014-07-01

The objective of this 3-arm parallel randomized clinical trial was to compare the effectiveness of temporary anchorage devices (TADs), Nance button palatal arches, and headgear for anchorage supplementation in the treatment of patients with malocclusions that required maximum anchorage. This trial was conducted between August 2008 and February 2013 in 2 orthodontic departments in the United Kingdom. The study included 78 patients (ages, 12-18 years; mean age, 14.2 years) who needed maximum anchorage. Eligibility criteria included no active caries, exemplary oral hygiene, and maximum anchorage required. The primary outcome was mesial molar movement during the period in which anchorage supplementation was required. The secondary outcomes were duration of anchorage reinforcement, number of treatment visits, number of casual and failed appointments, total treatment time, dento-occlusal change, and patients' perceptions of the method of anchorage supplementation. Treatment allocation was implemented by contacting via the Internet the randomization center at the University of Nottingham, Clinical Trials Unit. The randomization was based on a computer-generated pseudo-random code with random permuted blocks of randomly varying size. A research assistant who was blinded to the group allocation recorded all data. The patients were randomly allocated to receive anchorage supplementation with TADs, a Nance button on a palatal arch, or headgear. They were all treated with maxillary and mandibular preadjusted edgewise fixed appliances with 0.022-in slot prescription brackets. They were followed until orthodontic treatment was complete. Seventy-eight patients were randomized in a 1:1:1 ratio among the 3 groups. The baseline characteristics were similar in the groups, and they were treated for an average of 27.4 months (SD, 7.1 months); 71 completed orthodontic treatment. The data were analyzed on a per-protocol basis and showed no differences in the effectiveness of anchorage supplementation between TADs, Nance button palatal arches, and headgear. Compared with headgear, the average mesial movements of the maxillary right molar were 0.62 mm (-0.32 to 1.55 mm) with the Nance and -0.58 mm (-1.53 to 0.36 mm) with TADs; the maxillary left molar was moved -0.09 mm (-1.00 to 0.83 mm) with the Nance and -0.96 mm (-1.89 to -0.04 mm) with the TADs. Peer assessment rating scores were significantly better with the TADs than in the headgear and Nance groups. The patient questionnaires showed that comfort levels on placement of the TADs and the Nance were similar. Headgear was more troublesome and less popular with the patients. There was no difference in the effectiveness between the 3 groups in terms of anchorage support. There were more problems with the headgear and Nance buttons than with the TADs. The quality of treatment was better with TADs. As a result, TADS might be the preferred method for reinforcing orthodontic anchorage in patients who need maximum anchorage. ClinicalTrials.gov Identifier: NCT00995436. The protocol was published on the above site before the trial commencement. The British Orthodontic Society Foundation funded the study and American Orthodontics provided all the TADs and associated equipment. Copyright © 2014 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Zhen gan xi feng decoction, a traditional chinese herbal formula, for the treatment of essential hypertension: a systematic review of randomized controlled trials.

PubMed

Xiong, Xingjiang; Yang, Xiaochen; Feng, Bo; Liu, Wei; Duan, Lian; Gao, Ao; Li, Haixia; Ma, Jizheng; Du, Xinliang; Li, Nan; Wang, Pengqian; Su, Kelei; Chu, Fuyong; Zhang, Guohao; Li, Xiaoke; Wang, Jie

2013-01-01

Objectives. To assess the clinical effectiveness and adverse effects of Zhen Gan Xi Feng Decoction (ZGXFD) for essential hypertension (EH). Methods. Five major electronic databases were searched up to August 2012 to retrieve any potential randomized controlled trials designed to evaluate the clinical effectiveness of ZGXFD for EH reported in any language, with main outcome measure as blood pressure (BP). Results. Six randomized trials were included. Methodological quality of the trials was evaluated as generally low. Four trials compared prescriptions based on ZGXFD with antihypertensive drugs. Meta-analysis showed that ZGXFD was more effective in BP control and TCM syndrome and symptom differentiation (TCM-SSD) scores than antihypertensive drugs. Two trials compared the combination of modified ZGXFD plus antihypertensive drugs with antihypertensive drugs. Meta-analysis showed that there is significant beneficial effect on TCM-SSD scores. However, no significant effect on BP was found. The safety of ZGXFD is still uncertain. Conclusions. ZGXFD appears to be effective in improving blood pressure and hypertension-related symptoms for EH. However, the evidence remains weak due to poor methodological quality of the included studies. More rigorous trials are warranted to support their clinical use.

Surgical treatment for women with breast cancer: do randomized clinical trials represent current medical practices?

PubMed

Frederick, Wayne A I; Ames, Sarah; Downing, Stephanie R; Oyetunji, Tolulope A; Chang, David C; Leffall, Lasalle D

2010-06-01

Randomized clinical trials have not shown survival differences between breast cancer patients who undergo breast-conserving surgery and those who undergo modified radical mastectomy (MRM). Recent studies however, have suggested that these randomized clinical trials findings may not be representative of the entire population or the nature of current patient care. A retrospective analysis of female invasive breast cancer patients who underwent surgery in the Surveillance, Epidemiology, and End Results database (1990-2003) was performed. Survival was compared amongst women who underwent partial mastectomy, partial mastectomy plus radiation (PMR), or MRM. Cox proportional hazards regressions were used to investigate the impact of method of treatment upon survival, after adjusting for patient and tumor characteristics. A total of 218,043 patients, mean age 62 years, were identified. MRM accounted for 51.5 per cent of the study population whereas PMR accounted for 34.9 per cent. On multivariate analyses, significant improvement was observed in patient survival associated with PMR when compared with MRM patients (hazard ratio = 0.71, 95% confidence interval = 0.67-0.74, P < 0.001). This population-based study suggests that there is a survival benefit for women undergoing PMR in the treatment of breast cancer.

Customizing elastic pressure bandages for reuse to a predetermined, sub-bandage pressure: A randomized controlled trial.

PubMed

Sermsathanasawadi, Nuttawut; Tarapongpun, Tanakorn; Pianchareonsin, Rattana; Puangpunngam, Nattawut; Wongwanit, Chumpol; Chinsakchai, Khamin; Mutirangura, Pramook; Ruangsetakit, Chanean

2017-01-01

Objective A randomized clinical trial was performed to compare the effectiveness of unmarked bandages and customized bandages with visual markers in reproducing the desired sub-bandage pressure during self-bandaging by patients. Method Ninety patients were randomly allocated to two groups ("customized bandages" and "unmarked bandages") and asked to perform self-bandaging three times. The achievement of a pressure between 35 and 45 mmHg in at least two of the three attempts was defined as adequate quality. Results Adequate quality was achieved by 33.0% when applying the unmarked bandages, and 60.0% when applying the customized bandages ( p = 0.02). Use of the customized bandage and previous experience of bandaging were independent predictors for the achievement of the predetermined sub-bandage pressure ( p = 0.005 and p = 0.021, respectively). Conclusion Customized bandages may achieve predetermined sub-bandage pressures more closely than standard, unmarked, compression bandages. Clinical trials registration ClinicalTrials.gov (NCT02729688). Effectiveness of a Pressure Indicator Guided and a Conventional Bandaging in Treatment of Venous Leg Ulcer. https://clinicaltrials.gov/ct2/show/NCT02729688.

[METHODS OF EVALUATION OF MUSCLE MASS: A SYSTEMATIC REVIEW OF RANDOMIZED CONTROLLED TRIALS].

PubMed

Moreira, Osvaldo Costa; de Oliveira, Cláudia Eliza Patrocínio; Candia-Luján, Ramón; Romero-Pérez, Ena Monserrat; de Paz Fernandez, José Antonio

2015-09-01

in recent years, research about muscle mass has gained popularity for their relationship to health. Thus precise measurement of muscle mass may have clinical application once may interfere with the diagnosis and prescription drug or drug treatment. to conduct a systematic review of the methods most used for evaluation of muscle mass in randomized controlled trials, with its advantages and disadvantages. we conducted a search of the data bases Pub- Med, Web of Science and Scopus, with words "muscle mass", "measurement", "assessment" and "evaluation", combined in this way: "muscle mass" AND (assessment OR measurement OR evaluation). 23 studies were recovered and analyzed, all in English. 69.56% only used a method for quantification of muscle mass; 69.57% used dual X-ray absorptiometry (DXA); in 45.46% the type of measure used was the body lean mass; and 51.61% chose the whole body as a site of measurement. in the randomized controlled trials analyzed the majority used just one method of assessment, with the DXA being the method most used, the body lean mass the measurement type most used and total body the most common site of measure. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

A Two-Stage Estimation Method for Random Coefficient Differential Equation Models with Application to Longitudinal HIV Dynamic Data.

PubMed

Fang, Yun; Wu, Hulin; Zhu, Li-Xing

2011-07-01

We propose a two-stage estimation method for random coefficient ordinary differential equation (ODE) models. A maximum pseudo-likelihood estimator (MPLE) is derived based on a mixed-effects modeling approach and its asymptotic properties for population parameters are established. The proposed method does not require repeatedly solving ODEs, and is computationally efficient although it does pay a price with the loss of some estimation efficiency. However, the method does offer an alternative approach when the exact likelihood approach fails due to model complexity and high-dimensional parameter space, and it can also serve as a method to obtain the starting estimates for more accurate estimation methods. In addition, the proposed method does not need to specify the initial values of state variables and preserves all the advantages of the mixed-effects modeling approach. The finite sample properties of the proposed estimator are studied via Monte Carlo simulations and the methodology is also illustrated with application to an AIDS clinical data set.

Efficacy and safety of acupuncture for chronic dizziness: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Dizziness is one of the most challenging symptoms in medicine. No medication for dizziness in current use has well-established curative or prophylactic value or is suitable for long-term palliative use. Unconventional remedies, such as acupuncture, should be considered and scientifically evaluated. However, there has been relatively little evidence in randomized controlled clinical trials on acupuncture to treat chronic dizziness. The aim of our study is to evaluate the efficacy and safety of acupuncture in patients with dizziness. Methods/Design This trial is a randomized, single-blind, controlled study. A total of 80 participants will be randomly assigned to two treatment groups receiving acupuncture and sham acupuncture treatment, respectively, for 4 weeks. The primary outcome measures are the Dizziness Handicap Inventory (DHI) and the Vertigo Symptom Scale (VSS). Treatment will be conducted over a period of 4 weeks, at a frequency of two sessions per week. The assessment is at baseline (before treatment initiation), 4 weeks after the first acupuncture session, and 8 weeks after the first acupuncture session. Discussion The results from this study will provide clinical evidence on the efficacy and safety of acupuncture in patients with chronic dizziness. Trial registration International Standard Randomized Controlled Trial Number Register: ISRCTN52695239 PMID:24330810

Modular Approach to Therapy for Anxiety, Depression, Trauma, or Conduct Problems in outpatient child and adolescent mental health services in New Zealand: study protocol for a randomized controlled trial.

PubMed

Lucassen, Mathijs F G; Stasiak, Karolina; Crengle, Sue; Weisz, John R; Frampton, Christopher M A; Bearman, Sarah Kate; Ugueto, Ana M; Herren, Jennifer; Cribb-Su'a, Ainsleigh; Faleafa, Monique; Kingi-'Ulu'ave, Denise; Loy, Jik; Scott, Rebecca M; Hartdegen, Morgyn; Merry, Sally N

2015-10-12

Mental health disorders are common and disabling for young people because of the potential to disrupt key developmental tasks. Implementation of evidence-based psychosocial therapies in New Zealand is limited, owing to the inaccessibility, length, and cost of training in these therapies. Furthermore, most therapies address one problem area at a time, although comorbidity and changing clinical needs commonly occur in practice. A more flexible approach is needed. The Modular Approach to Therapy for Children with Anxiety, Depression, Trauma, or Conduct Problems (MATCH-ADTC) is designed to overcome these challenges; it provides a range of treatment modules addressing different problems, within a single training program. A clinical trial of MATCH-ADTC in the USA showed that MATCH-ADTC outperformed usual care and standard evidence-based treatment on several clinical measures. We aim to replicate these findings and evaluate the impact of providing training and supervision in MATCH-ADTC to: (1) improve clinical outcomes for youth attending mental health services; (2) increase the amount of evidence-based therapy content; (3) increase the efficiency of service delivery. This is an assessor-blinded multi-site effectiveness randomized controlled trial. Randomization occurs at two levels: (1) clinicians (≥60) are randomized to intervention or usual care; (2) youth participants (7-14 years old) accepted for treatment in child and adolescent mental health services (with a primary disorder that includes anxiety, depression, trauma-related symptoms, or disruptive behavior) are randomly allocated to receive MATCH-ADTC or usual care. Youth participants are recruited from 'mainstream', Māori-specific, and Pacific-specific child and adolescent mental health services. We originally planned to recruit 400 youth participants, but this has been revised to 200 participants. Centralized computer randomization ensures allocation concealment. The primary outcome measures are: (i) the difference in trajectory of change of clinical severity between groups (using the parent-rated Brief Problem Monitor); (ii) clinicians' use of evidence-based treatment procedures during therapy sessions; (iii) total time spent by clinicians delivering therapy. If MATCH-ADTC demonstrates effectiveness it could offer a practical efficient method to increase access to evidence-based therapies, and improve outcomes for youth attending secondary care services. Australian and New Zealand Clinical Trials Registry ACTRN12614000297628 .

Post-trial follow-up methodology in large randomized controlled trials: a systematic review protocol.

PubMed

Llewellyn-Bennett, Rebecca; Bowman, Louise; Bulbulia, Richard

2016-12-15

Clinical trials typically have a relatively short follow-up period, and may both underestimate potential benefits of treatments investigated, and fail to detect hazards, which can take much longer to emerge. Prolonged follow-up of trial participants after the end of the scheduled trial period can provide important information on both efficacy and safety outcomes. This protocol describes a systematic review to qualitatively compare methods of post-trial follow-up used in large randomized controlled trials. A systematic search of electronic databases and clinical trial registries will use a predefined search strategy. All large (more than 1000 adult participants) randomized controlled trials will be evaluated. Two reviewers will screen and extract data according to this protocol with the aim of 95% concordance of papers checked and discrepancies will be resolved by a third reviewer. Trial methods, participant retention rates and prevalence of missing data will be recorded and compared. The potential for bias will be evaluated using the Cochrane Risk of Bias tool (applied to the methods used during the in-trial period) with the aim of investigating whether the quality of the post-trial follow-up methodology might be predicted by the quality of the methods used for the original trial. Post-trial follow-up can provide valuable information about the long-term benefits and hazards of medical interventions. However, it can be logistically challenging and costly. The aim of this systematic review is to describe how trial participants have been followed-up post-trial in order to inform future post-trial follow-up designs. Not applicable for PROSPERO registration.

Research methods from social science can contribute much to the health sciences.

PubMed

Wensing, Michel

2008-06-01

Research methods from social science, such as social network analysis, random coefficient modeling, and advanced measurement techniques, can contribute much to the health sciences. There is, however, a slow rate of transmission of social science methodology into the health sciences. This paper identifies some of the barriers for adoption and proposes ideas for the future. Commentary. Contributions of social science to the health sciences are not always recognized as such. It may help if the professional profile of social science in the health sciences would be higher and if its focus would be more on making useful predictions. Clinical epidemiologists may assume that their discipline includes all relevant methods and that social science is largely based on qualitative research. These perceptions need to be challenged in order to widen the scope of clinical epidemiology and include relevant methods from other sciences. New methods help to ask new research questions and to provide better to old questions. This paper has sketched challenges for both social science researchers and clinical epidemiologists.

Impact of weight loss on ankle-brachial index and interartery blood pressures

USDA-ARS?s Scientific Manuscript database

Objective: To assess whether weight loss improves markers of peripheral artery disease and vascular stenosis. Methods: The Action for Health in Diabetes randomized clinical trial compared intensive lifestyle intervention (ILI) for weight loss to a control condition of diabetes support and education...

The role of gender in a smoking cessation intervention: a cluster randomized clinical trial

PubMed Central

2011-01-01

Background The prevalence of smoking in Spain is high in both men and women. The aim of our study was to evaluate the role of gender in the effectiveness of a specific smoking cessation intervention conducted in Spain. Methods This study was a secondary analysis of a cluster randomized clinical trial in which the randomization unit was the Basic Care Unit (family physician and nurse who care for the same group of patients). The intervention consisted of a six-month period of implementing the recommendations of a Clinical Practice Guideline. A total of 2,937 current smokers at 82 Primary Care Centers in 13 different regions of Spain were included (2003-2005). The success rate was measured by a six-month continued abstinence rate at the one-year follow-up. A logistic mixed-effects regression model, taking Basic Care Units as random-effect parameter, was performed in order to analyze gender as a predictor of smoking cessation. Results At the one-year follow-up, the six-month continuous abstinence quit rate was 9.4% in men and 8.5% in women (p = 0.400). The logistic mixed-effects regression model showed that women did not have a higher odds of being an ex-smoker than men after the analysis was adjusted for confounders (OR adjusted = 0.9, 95% CI = 0.7-1.2). Conclusions Gender does not appear to be a predictor of smoking cessation at the one-year follow-up in individuals presenting at Primary Care Centers. ClinicalTrials.gov Identifier NCT00125905. PMID:21605389

Comparative effectiveness of next generation genomic sequencing for disease diagnosis: design of a randomized controlled trial in patients with colorectal cancer/polyposis syndromes.

PubMed

Gallego, Carlos J; Bennette, Caroline S; Heagerty, Patrick; Comstock, Bryan; Horike-Pyne, Martha; Hisama, Fuki; Amendola, Laura M; Bennett, Robin L; Dorschner, Michael O; Tarczy-Hornoch, Peter; Grady, William M; Fullerton, S Malia; Trinidad, Susan B; Regier, Dean A; Nickerson, Deborah A; Burke, Wylie; Patrick, Donald L; Jarvik, Gail P; Veenstra, David L

2014-09-01

Whole exome and whole genome sequencing are applications of next generation sequencing transforming clinical care, but there is little evidence whether these tests improve patient outcomes or if they are cost effective compared to current standard of care. These gaps in knowledge can be addressed by comparative effectiveness and patient-centered outcomes research. We designed a randomized controlled trial that incorporates these research methods to evaluate whole exome sequencing compared to usual care in patients being evaluated for hereditary colorectal cancer and polyposis syndromes. Approximately 220 patients will be randomized and followed for 12 months after return of genomic findings. Patients will receive findings associated with colorectal cancer in a first return of results visit, and findings not associated with colorectal cancer (incidental findings) during a second return of results visit. The primary outcome is efficacy to detect mutations associated with these syndromes; secondary outcomes include psychosocial impact, cost-effectiveness and comparative costs. The secondary outcomes will be obtained via surveys before and after each return visit. The expected challenges in conducting this randomized controlled trial include the relatively low prevalence of genetic disease, difficult interpretation of some genetic variants, and uncertainty about which incidental findings should be returned to patients. The approaches utilized in this study may help guide other investigators in clinical genomics to identify useful outcome measures and strategies to address comparative effectiveness questions about the clinical implementation of genomic sequencing in clinical care. Copyright © 2014 Elsevier Inc. All rights reserved.

[Recent and upcoming randomized trials for left atrial appendage occlusion : Need for a definite assessment of the situation].

PubMed

Skurk, Carsten; Hartung, Johannes Jakob; Landmesser, Ulf

2017-12-01

Atrial fibrillation (AF) is the most common arrhythmia affecting more than 1.6 million patients in Germany. Based on demographic developments, an the number is expected to increase. Embolic strokes in AF patients are particularly severe, and individualized new oral anticoagulant (NOAC) therapy reduces the incidence of stroke in these patients by approximately 70%. Besides vitamin K antagonists, the NOACs rivaroxaban, dabigatran, apixaban, and edoxaban have been introduced into clinical practice; however, major bleeding still occurs at a rate of 2-3% per year. Moreover, randomized studies and real-life registries suggest that >20% of patients with AF and an indication for anticoagulation cannot tolerate chronic oral anticoagulant therapy. Therefore, an alternative method for stroke prevention in AF patients has been developed, i. e., catheter-based exclusion of the left atrial appendage (LAA), a location that is prone for thrombus formation in these patients. The randomized trials of catheter-based LAA occlusion have compared this interventional therapy with vitamin K antagonists. In the future, however, LAA exclusion needs to be compared with NOAC therapy. Moreover, percutaneous LAA exclusion in clinical practice is mostly offered to patients ineligible for long-term oral anticoagulation or with high bleeding risk. However, no controlled, randomized trial data exist for this patient population. These data are needed for appropriate clinical judgment and optimal clinical management. Ongoing studies and scientific questions that are important to define the future for catheter-based LAA closure are discussed in this review.

Role of Statistical Random-Effects Linear Models in Personalized Medicine

PubMed Central

Diaz, Francisco J; Yeh, Hung-Wen; de Leon, Jose

2012-01-01

Some empirical studies and recent developments in pharmacokinetic theory suggest that statistical random-effects linear models are valuable tools that allow describing simultaneously patient populations as a whole and patients as individuals. This remarkable characteristic indicates that these models may be useful in the development of personalized medicine, which aims at finding treatment regimes that are appropriate for particular patients, not just appropriate for the average patient. In fact, published developments show that random-effects linear models may provide a solid theoretical framework for drug dosage individualization in chronic diseases. In particular, individualized dosages computed with these models by means of an empirical Bayesian approach may produce better results than dosages computed with some methods routinely used in therapeutic drug monitoring. This is further supported by published empirical and theoretical findings that show that random effects linear models may provide accurate representations of phase III and IV steady-state pharmacokinetic data, and may be useful for dosage computations. These models have applications in the design of clinical algorithms for drug dosage individualization in chronic diseases; in the computation of dose correction factors; computation of the minimum number of blood samples from a patient that are necessary for calculating an optimal individualized drug dosage in therapeutic drug monitoring; measure of the clinical importance of clinical, demographic, environmental or genetic covariates; study of drug-drug interactions in clinical settings; the implementation of computational tools for web-site-based evidence farming; design of pharmacogenomic studies; and in the development of a pharmacological theory of dosage individualization. PMID:23467392

A smart rotary technique versus conventional pulpectomy for primary teeth: A randomized controlled clinical study

PubMed Central

Mokhtari, Negar; Shirazi, Alireza-Sarraf

2017-01-01

Background Techniques with adequate accuracy of working length determination along with shorter duration of treatment in pulpectomy procedure seems to be essential in pediatric dentistry. The aim of the present study was to evaluate the accuracy of root canal length measurement with Root ZX II apex locator and rotary system in pulpectomy of primary teeth. Material and Methods In this randomized control clinical trial complete pulpectomy was performed on 80 mandibular primary molars in 80, 4-6-year-old children. The study population was randomly divided into case and control groups. In control group conventional pulpectomy was performed and in the case group working length was determined by electronic apex locator Root ZXII and instrumented with Mtwo rotary files. Statistical evaluation was performed using Mann-Whitney and Chi-Square tests (P<0.05). Results There were no significant differences between electronic apex locator Root ZXII and conventional method in accuracy of root canal length determination. However significantly less time was needed for instrumenting with rotary files (P=0.000). Conclusions Considering the comparable results in accuracy of root canal length determination and the considerably shorter instrumentation time in Root ZXII apex locator and rotary system, it may be suggested for pulpectomy in primary molar teeth. Key words:Rotary technique, conventional technique, pulpectomy, primary teeth. PMID:29302280

Randomized algorithms for high quality treatment planning in volumetric modulated arc therapy

NASA Astrophysics Data System (ADS)

Yang, Yu; Dong, Bin; Wen, Zaiwen

2017-02-01

In recent years, volumetric modulated arc therapy (VMAT) has been becoming a more and more important radiation technique widely used in clinical application for cancer treatment. One of the key problems in VMAT is treatment plan optimization, which is complicated due to the constraints imposed by the involved equipments. In this paper, we consider a model with four major constraints: the bound on the beam intensity, an upper bound on the rate of the change of the beam intensity, the moving speed of leaves of the multi-leaf collimator (MLC) and its directional-convexity. We solve the model by a two-stage algorithm: performing minimization with respect to the shapes of the aperture and the beam intensities alternatively. Specifically, the shapes of the aperture are obtained by a greedy algorithm whose performance is enhanced by random sampling in the leaf pairs with a decremental rate. The beam intensity is optimized using a gradient projection method with non-monotonic line search. We further improve the proposed algorithm by an incremental random importance sampling of the voxels to reduce the computational cost of the energy functional. Numerical simulations on two clinical cancer date sets demonstrate that our method is highly competitive to the state-of-the-art algorithms in terms of both computational time and quality of treatment planning.

Comparison of clinical efficacy and safety of thermotherapy versus cryotherapy in treatment of skin warts: A randomized controlled trial.

PubMed

Izadi Firouzabadi, Leila; Khamesipour, Ali; Ghandi, Narges; Hosseini, Hamed; Teymourpour, Amir; Firooz, Alireza

2018-01-01

The effect of thermotherapy in the treatment of skin warts in comparison to cryotherapy, as the standard conventional method, has remained uncertain. This study aimed to assess the clinical efficacy and safety of thermotherapy and cryotherapy in removing skin warts. This randomized controlled trial was conducted on 52 patients aged 18 years and over with ≤ 10 skin warts. The participants were randomly assigned into two groups to receive cryotherapy (every 2 to 3 weeks up to six sessions if required) or thermotherapy (one session). The patients in both groups were followed every 2 to 3 weeks for the first three months, and then three months after the last treatment session. The clearance rate was 79.2% in the thermotherapy group and 58.3% in the cryotherapy group with no significant difference (p = 0.212). The rate of scarring in the thermotherapy group was 20% (p = .018). A higher clearance rate was achieved in the thermotherapy group. However, this result was not statistically significant. There were some minimal post-treatment complications. Patients needed only one session of thermotherapy. Due to the risk of scarring, we suggest thermotherapy only as a suitable treatment method for palmoplantar warts. © 2017 Wiley Periodicals, Inc.

Zeta Sperm Selection Improves Pregnancy Rate and Alters Sex Ratio in Male Factor Infertility Patients: A Double-Blind, Randomized Clinical Trial

PubMed Central

Nasr Esfahani, Mohammad Hossein; Deemeh, Mohammad Reza; Tavalaee, Marziyeh; Sekhavati, Mohammad Hadi; Gourabi, Hamid

2016-01-01

Background Selection of sperm for intra-cytoplasmic sperm injection (ICSI) is usually considered as the ultimate technique to alleviate male-factor infertility. In routine ICSI, selection is based on morphology and viability which does not necessarily preclude the chance injection of DNA-damaged or apoptotic sperm into the oocyte. Sperm with high negative surface electrical charge, named “Zeta potential”, are mature and more likely to have intact chromatin. In addition, X-bearing spermatozoa carry more negative charge. Therefore, we aimed to compare the clinical outcomes of Zeta procedure with routine sperm selection in infertile men candidate for ICSI. Materials and Methods From a total of 203 ICSI cycles studied, 101 cycles were allocated to density gradient centrifugation (DGC)/Zeta group and the remaining 102 were included in the DGC group in this prospective study. Clinical outcomes were com- pared between the two groups. The ratios of Xand Y bearing sperm were assessed by fluorescence in situ hybridization (FISH) and quantitative polymerase chain reaction (qPCR) methods in 17 independent semen samples. Results In the present double-blind randomized clinical trial, a significant increase in top quality embryos and pregnancy rate were observed in DGC/Zeta group compared to DGC group. Moreover, sex ratio (XY/XX) at birth significantly was lower in the DGC/Zeta group compared to DGC group despite similar ratio of X/Y bearings sper- matozoa following Zeta selection. Conclusion Zeta method not only improves the percentage of top embryo quality and pregnancy outcome but also alters the sex ratio compared to the conventional DGC method, despite no significant change in the ratio of Xand Ybearing sperm population (Registration number: IRCT201108047223N1). PMID:27441060

Linguistic Strategies for Improving Informed Consent in Clinical Trials Among Low Health Literacy Patients

PubMed Central

Neil, Jordan M.; Strekalova, Yulia A.; Sarge, Melanie A.

2017-01-01

Abstract Background: Improving informed consent to participate in randomized clinical trials (RCTs) is a key challenge in cancer communication. The current study examines strategies for enhancing randomization comprehension among patients with diverse levels of health literacy and identifies cognitive and affective predictors of intentions to participate in cancer RCTs. Methods: Using a post-test-only experimental design, cancer patients (n = 500) were randomly assigned to receive one of three message conditions for explaining randomization (ie, plain language condition, gambling metaphor, benign metaphor) or a control message. All statistical tests were two-sided. Results: Health literacy was a statistically significant moderator of randomization comprehension (P = .03). Among participants with the lowest levels of health literacy, the benign metaphor resulted in greater comprehension of randomization as compared with plain language (P = .04) and control (P = .004) messages. Among participants with the highest levels of health literacy, the gambling metaphor resulted in greater randomization comprehension as compared with the benign metaphor (P = .04). A serial mediation model showed a statistically significant negative indirect effect of comprehension on behavioral intention through personal relevance of RCTs and anxiety associated with participation in RCTs (P < .001). Conclusions: The effectiveness of metaphors for explaining randomization depends on health literacy, with a benign metaphor being particularly effective for patients at the lower end of the health literacy spectrum. The theoretical model demonstrates the cognitive and affective predictors of behavioral intention to participate in cancer RCTs and offers guidance on how future research should employ communication strategies to improve the informed consent processes. PMID:27794035

Cellular replacement therapy for Parkinson's disease--where we are today?

PubMed

Redmond, D Eugene

2002-10-01

The concept of replacing lost dopamine neurons in Parkinson's disease using mesencephalic brain cells from fetal cadavers has been supported by over 20 years of research in animals and over a decade of clinical studies. The ambitious goal of these studies was no less than a molecular and cellular "cure" for Parkinson's disease, other neurodegenerative diseases, and spinal cord injury. Much research has been done in rodents, and a few studies have been done in nonhuman primate models. Early uncontrolled clinical reports were enthusiastic, but the outcome of the first randomized, double blind, controlled study challenged the idea that dopamine replacement cells can cure Parkinson's disease, although there were some significant positive findings. Were the earlier animal studies and clinical reports wrong? Should we give up on the goal? Some aspects of the trial design and implantation methods may have led to lack of effects and to some side effects such as dyskinesias. But a detailed review of clinical neural transplants published to date still suggests that neural transplantation variably reverses some aspects of Parkinson's disease, although differing methods make exact comparisons difficult. While the randomized clinical studies have been in progress, new methods have shown promise for increasing transplant survival and distribution, reconstructing the circuits to provide dopamine to the appropriate targets and with normal regulation. Selected promising new strategies are reviewed that block apoptosis induced by tissue dissection, promote vascularization of grafts, reduce oxidant stress, provide key growth factors, and counteract adverse effects of increased age. New sources of replacement cells and stem cells may provide additional advantages for the future. Full recovery from parkinsonism appears not only to be possible, but a reliable cell replacement treatment may finally be near.

Distance management of inflammatory bowel disease: Systematic review and meta-analysis

PubMed Central

Huang, Vivian W; Reich, Krista M; Fedorak, Richard N

2014-01-01

AIM: To review the effectiveness of distance management methods in the management of adult inflammatory bowel disease (IBD) patients. METHODS: A systematic review and meta-analysis of randomized controlled trials comparing distance management and standard clinic follow-up in the management of adult IBD patients. Distance management intervention was defined as any remote management method in which there is a patient self-management component whereby the patient interacts remotely via a self-guided management program, electronic interface, or self-directs open access to clinic follow up. The search strategy included electronic databases (Medline, PubMed, CINAHL, The Cochrane Central Register of Controlled Trials, EMBASE, KTPlus, Web of Science, and SCOPUS), conference proceedings, and internet search for web publications. The primary outcome was the mean difference in quality of life, and the secondary outcomes included mean difference in relapse rate, clinic visit rate, and hospital admission rate. Study selection, data extraction, and risk of bias assessment were completed by two independent reviewers. RESULTS: The search strategy identified a total of 4061 articles, but only 6 randomized controlled trials met the inclusion and exclusion criteria for the systematic review and meta-analysis. Three trials involved telemanagement, and three trials involved directed patient self-management and open access clinics. The total sample size was 1463 patients. There was a trend towards improved quality of life in distance management patients with an end IBDQ quality of life score being 7.28 (95%CI: -3.25-17.81) points higher than standard clinic follow-up. There was a significant decrease in the clinic visit rate among distance management patients mean difference -1.08 (95%CI: -1.60--0.55), but no significant change in relapse rate or hospital admission rate. CONCLUSION: Distance management of IBD significantly decreases clinic visit utilization, but does not significantly affect relapse rates or hospital admission rates. PMID:24574756

COACH trial: A randomized controlled trial of nurse practitioner/community health worker cardiovascular disease risk reduction in urban community health centers: Rationale and design

PubMed Central

Allen, Jerilyn K; Himmelfarb, Cheryl R Dennison; Szanton, Sarah L; Bone, Lee; Hill, Martha N; Levine, David M

2011-01-01

Background Despite well-publicized guidelines on the appropriate management of cardiovascular disease (CVD) and type 2 diabetes, implementation of risk-reducing practices remains poor. This paper describes the rationale and design of a randomized controlled clinical trial evaluating the effectiveness of a comprehensive program of CVD risk reduction delivered by nurse practitioner (NP)/community health worker (CHW) teams versus enhanced usual care in improving the proportion of patients in urban community health centers who achieve goal levels recommended by national guidelines for lipids, blood pressure, HbA1c and prescription of appropriate medications. Methods The COACH (Community Outreach and Cardiovascular Health) trial is a randomized controlled trial in which patients at federally-qualified community health centers were randomly assigned to one of two groups: comprehensive intensive management of CVD risk factors for one year by a NP/CHW team or an enhanced usual care control group. Results A total of 3899 patients were assessed for eligibility and 525 were randomized. Groups were comparable at baseline on sociodemographic and clinical characteristics with the exception of statistically significant differences in total cholesterol and hemoglobin A1c. Conclusions This study is a novel amalgam of multilevel interdisciplinary strategies to translate highly efficacious therapies to low-income federally-funded health centers that care for patients who carry a disproportionate burden of CVD, type 2 diabetes and uncontrolled CVD risk factors. The impact of such a community clinic-based intervention is potentially enormous. PMID:21241828

Detrended Fluctuation Analysis and Adaptive Fractal Analysis of Stride Time Data in Parkinson's Disease: Stitching Together Short Gait Trials

PubMed Central

Liebherr, Magnus; Haas, Christian T.

2014-01-01

Variability indicates motor control disturbances and is suitable to identify gait pathologies. It can be quantified by linear parameters (amplitude estimators) and more sophisticated nonlinear methods (structural information). Detrended Fluctuation Analysis (DFA) is one method to measure structural information, e.g., from stride time series. Recently, an improved method, Adaptive Fractal Analysis (AFA), has been proposed. This method has not been applied to gait data before. Fractal scaling methods (FS) require long stride-to-stride data to obtain valid results. However, in clinical studies, it is not usual to measure a large number of strides (e.g., strides). Amongst others, clinical gait analysis is limited due to short walkways, thus, FS seem to be inapplicable. The purpose of the present study was to evaluate FS under clinical conditions. Stride time data of five self-paced walking trials ( strides each) of subjects with PD and a healthy control group (CG) was measured. To generate longer time series, stride time sequences were stitched together. The coefficient of variation (CV), fractal scaling exponents (DFA) and (AFA) were calculated. Two surrogate tests were performed: A) the whole time series was randomly shuffled; B) the single trials were randomly shuffled separately and afterwards stitched together. CV did not discriminate between PD and CG. However, significant differences between PD and CG were found concerning and . Surrogate version B yielded a higher mean squared error and empirical quantiles than version A. Hence, we conclude that the stitching procedure creates an artificial structure resulting in an overestimation of true . The method of stitching together sections of gait seems to be appropriate in order to distinguish between PD and CG with FS. It provides an approach to integrate FS as standard in clinical gait analysis and to overcome limitations such as short walkways. PMID:24465708

CONCEPTUAL AND METHODOLOGICAL ISSUES IN DESIGNING A RANDOMIZED CONTROLLED TREATMENT TRIAL FOR GERIATRIC BIPOLAR DISORDER: GERI-BD

PubMed Central

Young, Robert C.; Schulberg, Herbert C.; Gildengers, Ariel G.; Sajatovic, Martha; Mulsant, Benoit H.; Gyulai, Laszlo; Beyer, John; Marangell, Lauren; Kunik, Mark; Have, Thomas Ten; Bruce, Martha L.; Gur, Ruben; Marino, Patricia; Evans, Jovier D.; Reynolds, Charles F.; Alexopoulos, George S.

2010-01-01

Aim This report considers the conceptual and methodological concerns confronting clinical investigators seeking to generate knowledge regarding the tolerability and benefits of pharmacotherapy in geriatric bipolar (BP) patients. Method There is continuing need for evidence-based guidelines derived from randomized controlled trials that will enhance drug treatment of geriatric BP patients. We, therefore, present the complex conceptual and methodological choices encountered in designing a multi-site clinical trial and the decisions reached by the investigators with the intention that study findings are pertinent to, and can facilitate, routine treatment decisions. Results Guided by a literature review and input from peers, the tolerability and anti-manic effect of lithium and valproate were judged to be the key mood stabilizers to investigate with regard to treating BP I manic, mixed and hypomanic states. The patient selection criteria are intended to generate a sample that experiences common treatment needs but which also represents the variety of older patients seen in university-based clinical settings. The clinical protocol guides titratation of lithium and valproate to target serum concentrations, with lower levels allowed when necessitated by limited tolerability. The protocol emphasizes initial monotherapy. However, augmentation with risperidone is permitted after three weeks when indicated by operational criteria. Conclusions A randomized controlled trial that both investigates commonly prescribed mood stabilizers and maximizes patient participation can meaningfully address high priority clinical concerns directly relevant to the routine pharmacologic treatment of geriatric BP patients. PMID:20148867

Randomized clinical trials as reflexive-interpretative process in patients with rheumatoid arthritis: a qualitative study.

PubMed

de Jorge, Mercedes; Parra, Sonia; de la Torre-Aboki, Jenny; Herrero-Beaumont, Gabriel

2015-08-01

Patients in randomized clinical trials have to adapt themselves to a restricted language to capture the necessary information to determine the safety and efficacy of a new treatment. The aim of this study was to explore the experience of patients with rheumatoid arthritis after completing their participation in a biologic therapy randomized clinical trial for a period of 3 years. A qualitative approach was used. The information was collected using 15 semi-structured interviews of patients with rheumatoid arthritis. Data collection was guided by the emergent analysis until no more relevant variations in the categories were found. The data were analysed using the grounded theory method. The objective of the patients when entering the study was to improve their quality of life by initiating the treatment. However, the experience changed the significance of the illness as they acquired skills and practical knowledge related to the management of their disease. The category "Interactional Empowerment" emerged as core category, as it represented the participative experience in a clinical trial. The process integrates the follow categories: "weight of systematisation", "working together", and the significance of the experience: "the duties". Simultaneously these categories evolved. The clinical trial monitoring activities enabled patients to engage in a reflexive-interpretative mechanism that transformed the emotional and symbolic significance of their disease and improved the empowerment of the patient. A better communicative strategy with the health professionals, the relatives of the patients, and the community was also achieved.

Randomized controlled trials in mild cognitive impairment

PubMed Central

Thomas, Ronald G.; Aisen, Paul S.; Mohs, Richard C.; Carrillo, Maria C.; Albert, Marilyn S.

2017-01-01

Objective: To examine the variability in performance among placebo groups in randomized controlled trials for mild cognitive impairment (MCI). Methods: Placebo group data were obtained from 2 National Institute on Aging (NIA) MCI randomized controlled trials, the Alzheimer's Disease Cooperative Study (ADCS) MCI trial and the Alzheimer's Disease Neuroimaging Initiative (ADNI), which is a simulated clinical trial, in addition to industry-sponsored clinical trials involving rivastigmine, galantamine, rofecoxib, and donepezil. The data were collated for common measurement instruments. The performance of the placebo participants from these studies was tracked on the Alzheimer's Disease Assessment Scale–cognitive subscale, Mini-Mental State Examination, and Clinical Dementia Rating–sum of boxes, and for progression on these measures to prespecified clinical study endpoints. APOE status, where available, was also analyzed for its effects. Results: The progression to clinical endpoints varied a great deal among the trials. The expected performances were seen for the participants in the 2 NIA trials, ADCS and ADNI, with generally worsening of performance over time; however, the industry-sponsored trials largely showed stable or improved performance in their placebo participants. APOE4 carrier status influenced results in an expected fashion on the study outcomes, including rates of progression and cognitive subscales. Conclusions: In spite of apparently similar criteria for MCI being adopted by the 7 studies, the implementation of the criteria varied a great deal. Several explanations including instruments used to characterize participants and variability among study populations contributed to the findings. PMID:28381516

Design of the evolution of management strategies of heart failure patients with implantable defibrillators (EVOLVO) study to assess the ability of remote monitoring to treat and triage patients more effectively

PubMed Central

Marzegalli, Maurizio; Landolina, Maurizio; Lunati, Maurizio; Perego, Giovanni B; Pappone, Alessia; Guenzati, Giuseppe; Campana, Carlo; Frigerio, Maria; Parati, Gianfranco; Curnis, Antonio; Colangelo, Irene; Valsecchi, Sergio

2009-01-01

Background Heart failure patients with implantable defibrillators (ICD) frequently visit the clinic for routine device monitoring. Moreover, in the case of clinical events, such as ICD shocks or alert notifications for changes in cardiac status or safety issues, they often visit the emergency department or the clinic for an unscheduled visit. These planned and unplanned visits place a great burden on healthcare providers. Internet-based remote device interrogation systems, which give physicians remote access to patients' data, are being proposed in order to reduce routine and interim visits and to detect and notify alert conditions earlier. Methods The EVOLVO study is a prospective, randomized, parallel, unblinded, multicenter clinical trial designed to compare remote ICD management with the current standard of care, in order to assess its ability to treat and triage patients more effectively. Two-hundred patients implanted with wireless-transmission-enabled ICD will be enrolled and randomized to receive either the Medtronic CareLink® monitor for remote transmission or the conventional method of in-person evaluations. The purpose of this manuscript is to describe the design of the trial. The results, which are to be presented separately, will characterize healthcare utilizations as a result of ICD follow-up by means of remote monitoring instead of conventional in-person evaluations. Trial registration ClinicalTrials.gov: NCT00873899 PMID:19538734

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.

Biodegradable magnesium-based screw clinically equivalent to titanium screw in hallux valgus surgery: short term results of the first prospective, randomized, controlled clinical pilot study

PubMed Central

2013-01-01

Purpose Nondegradable steel-and titanium-based implants are commonly used in orthopedic surgery. Although they provide maximal stability, they are also associated with interference on imaging modalities, may induce stress shielding, and additional explantation procedures may be necessary. Alternatively, degradable polymer implants are mechanically weaker and induce foreign body reactions. Degradable magnesium-based stents are currently being investigated in clinical trials for use in cardiovascular medicine. The magnesium alloy MgYREZr demonstrates good biocompatibility and osteoconductive properties. The aim of this prospective, randomized, clinical pilot trial was to determine if magnesium-based MgYREZr screws are equivalent to standard titanium screws for fixation during chevron osteotomy in patients with a mild hallux valgus. Methods Patients (n=26) were randomly assigned to undergo osteosynthesis using either titanium or degradable magnesium-based implants of the same design. The 6 month follow-up period included clinical, laboratory, and radiographic assessments. Results No significant differences were found in terms of the American Orthopaedic Foot and Ankle Society (AOFAS) score for hallux, visual analog scale for pain assessment, or range of motion (ROM) of the first metatarsophalangeal joint (MTPJ). No foreign body reactions, osteolysis, or systemic inflammatory reactions were detected. The groups were not significantly different in terms of radiographic or laboratory results. Conclusion The radiographic and clinical results of this prospective controlled study demonstrate that degradable magnesium-based screws are equivalent to titanium screws for the treatment of mild hallux valgus deformities. PMID:23819489

Gingival Unit Graft Versus Free Gingival Graft for Treatment of Gingival Recession: A Randomized Controlled Clinical Trial

PubMed Central

Jenabian, Niloofar; Bahabadi, Mohadese Yazdanpanah; Bijani, Ali; Rad, Morteza Rahimi

2016-01-01

Objectives: Gingival recession can lead to root exposure and discomfort for patients. There are various techniques for root coverage. The aim of this study was to compare the use of gingival unit graft (palatal graft including the marginal gingiva and papillae) with free gingival graft for treatment of localized gingival recession. Materials and Methods: In this randomized controlled clinical trial, 18 bilateral localized recessions of Miller class I and II were treated in nine systemically healthy patients. Recessions were randomly treated with gingival unit graft in one side and conventional free gingival graft in the other side. Clinical parameters including clinical attachment level, keratinized tissue width, probing depth and vertical recession depth (VRD) were recorded at baseline and at one, three and six months after surgery. The healing index and patient satisfaction were also evaluated. One-way and two-way repeated measures ANOVA and paired t-test were used for statistical analyses. Results: Both techniques caused significant improvement in clinical parameters. Gingival unit graft produced higher satisfaction esthetically (P=0.050, 0.024 and 0.024, respectively at the three time points), higher healing index (P<0.001), higher root coverage percentage at one month after surgery (34.04%, P=0.011) and greater reduction of recession width three months after surgery (P=0.007) but the reduction in VRD at this side was not significantly greater. Conclusions: Gingival unit graft might be an acceptable modality in Miller Class I/II recession defects. This technique may have advantages over free gingival graft such as significantly superior clinical and esthetic results. PMID:28392815

Treatment of Anxiety in Patients with Coronary Heart Disease: Rationale and Design of the UNWIND Randomized Clinical Trial

PubMed Central

Blumenthal, James A.; Feger, Bryan J.; Smith, Patrick J.; Watkins, Lana L.; Jiang, Wei; Davidson, Jonathan; Hoffman, Benson M.; Ashworth, Megan; Mabe, Stephanie K.; Babyak, Michael A.; Kraus, William E.; Hinderliter, Alan; Sherwood, Andrew

2016-01-01

Background Anxiety is highly prevalent among patients with coronary heart disease (CHD), and there is growing evidence that high levels of anxiety are associated with worse prognosis. However, few studies have evaluated the efficacy of treating anxiety in CHD patients for reducing symptoms and improving clinical outcomes. Exercise and selective serotonin reuptake inhibitors have been shown to be effective in treating patients with depression, but have not been studied in cardiac patients with high anxiety. Methods The UNWIND trial is a randomized clinical trial of patients with CHD who are at increased risk for adverse events because of comorbid anxiety. One hundred fifty participants with CHD and elevated anxiety symptoms and/or with a diagnosed anxiety disorder will be randomly assigned to 12 weeks of aerobic exercise (3×/wk, 35 min, 70–85% VO2peak), escitalopram (5–20 mg qd), or placebo. Before and after 12 weeks of treatment, participants will undergo assessments of anxiety symptoms and CHD biomarkers of risk, including measures of inflammation, lipids, hemoglobin A1c, heart rate variability, and vascular endothelial function. Primary outcomes include post-intervention effects on symptoms of anxiety and CHD biomarkers. Secondary outcomes include clinical outcomes (cardiovascular hospitalizations and all-cause death) and measures of quality of life. Conclusions The UNWIND trial (ClinicalTrials.gov NCT02516332) will evaluate the efficacy of aerobic exercise and escitalopram for improving anxiety symptoms and reducing risk for adverse clinical events in anxious CHD patients. PMID:27264220

Comparison of the performance of rapid prescreening, 10% random review, and clinical risk criteria as methods of internal quality control in cervical cytopathology.

PubMed

Tavares, Suelene B N; Alves de Sousa, Nadja L; Manrique, Edna J C; Pinheiro de Albuquerque, Zair B; Zeferino, Luiz C; Amaral, Rita G

2008-06-25

Rapid prescreening (RPS) is an internal quality-control (IQC) method that is used both to reduce errors in the laboratory and to measure the sensitivity of routine screening (RS). Little direct comparison data are available comparing RPS with other more widely used IQC methods. The authors compared the performance of RPS, 10% random review of negative smears (R-10%), and directed rescreening of negative smears based on clinical risk criteria (RCRC) over 1 year in a community clinic setting. In total, 6,135 smears were evaluated. The sensitivity of RS alone was 71.3%. RPS detected significantly more (132 cases) false-negative (FN) cases than either R-10% (7 cases) or RCRC (32 cases). RPS significantly improved the overall sensitivity of the laboratory (71.3-92.2%; P = .001); neither R-10% nor RCRC significantly changed the sensitivity of RS. RPS was not as specific as the other methods, although nearly 68% of all abnormalities detected by RPS were verified as real. RPS of 100% of smears required the same amount of time as RCRC but required twice as much time as R-10%. The current results demonstrated that RPS is a much more effective IQC method than either R-10% or RCRC. RPS detects significantly more errors and can improve the overall sensitivity of a laboratory with either a modest increase or no increase in overall time spent on IQC. R-10% is an insensitive IQC method, and neither R-10% nor RCRC can significantly improve the overall sensitivity of a laboratory. (c) 2008 American Cancer Society.

Effects of Sex Education and Kegel Exercises on the Sexual Function of Postmenopausal Women: A Randomized Clinical Trial.

PubMed

Nazarpour, Soheila; Simbar, Masoumeh; Ramezani Tehrani, Fahimeh; Alavi Majd, Hamid

2017-07-01

The sex lives of women are strongly affected by menopause. Non-pharmacologic approaches to improving the sexual function of postmenopausal women might prove effective. To compare two methods of intervention (formal sex education and Kegel exercises) with routine postmenopausal care services in a randomized clinical trial. A randomized clinical trial was conducted of 145 postmenopausal women residing in Chalus and Noshahr, Iran. Their sexual function statuses were assessed using the Female Sexual Function Index (FSFI) questionnaire. After obtaining written informed consents, they were randomly assigned to one of three groups: (i) formal sex education, (ii) Kegel exercises, or (iii) routine postmenopausal care. After 12 weeks, all participants completed the FSFI again. Analysis of covariance was used to compare the participants' sexual function before and after the interventions, and multiple linear regression analysis was used to determine the predictive factors for variation in FSFI scores in the postintervention stage. Sexual function was assessed using the FSFI. There were no statistically significant differences in demographic and socioeconomic characteristics and FSFI total scores among the three study groups at the outset of the study. After 12 weeks, the scores of arousal in the formal sex education and Kegel groups were significantly higher compared with the control group (3.38 and 3.15 vs 2.77, respectively). The scores of orgasm and satisfaction in the Kegel group were significantly higher compared with the control group (4.43 and 4.88 vs 3.95 and 4.39, respectively). Formal sex education and Kegel exercises were used as two non-pharmacologic approaches to improve the sexual function of women after menopause. The main strength of this study was its design: a well-organized randomized trial using precise eligibility criteria with a small sample loss. The second strength was the methods of intervention used, namely non-pharmacologic approaches that are simple, easily accessible, and fairly inexpensive. The main limitation of the study was our inability to objectively assess the participants' commitment to exercise and the sexual function of their partners. Sex education programs and Kegel exercises could cause improvements in some domains of sexual function-specifically arousal, orgasm, and satisfaction-in postmenopausal women. Nazarpour S, Simbar M, Tehrani FR, Majd HA. Effects of Sex Education and Kegel Exercises on the Sexual Function of Postmenopausal Women: A Randomized Clinical Trial. J Sex Med 2017;14:959-967. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

A nonrandomized cohort and a randomized study of local control of large hepatocarcinoma by targeting intratumoral lactic acidosis

PubMed Central

Chao, Ming; Wu, Hao; Jin, Kai; Li, Bin; Wu, Jianjun; Zhang, Guangqiang; Yang, Gong; Hu, Xun

2016-01-01

Study design: Previous works suggested that neutralizing intratumoral lactic acidosis combined with glucose deprivation may deliver an effective approach to control tumor. We did a pilot clinical investigation, including a nonrandomized (57 patients with large HCC) and a randomized controlled (20 patients with large HCC) studies. Methods: The patients were treated with transarterial chemoembolization (TACE) with or without bicarbonate local infusion into tumor. Results: In the nonrandomized controlled study, geometric mean of viable tumor residues (VTR) in TACE with bicarbonate was 6.4-fold lower than that in TACE without bicarbonate (7.1% [95% CI: 4.6%–10.9%] vs 45.6% [28.9%–72.0%]; p<0.0001). This difference was recapitulated by a subsequent randomized controlled study. TACE combined with bicarbonate yielded a 100% objective response rate (ORR), whereas the ORR treated with TACE alone was 44.4% (nonrandomized) and 63.6% (randomized). The survival data suggested that bicarbonate may bring survival benefit. Conclusion: Bicarbonate markedly enhances the anticancer activity of TACE. Clinical trail registration: ChiCTR-IOR-14005319. DOI: http://dx.doi.org/10.7554/eLife.15691.001 PMID:27481188

A random walk rule for phase I clinical trials.

PubMed

Durham, S D; Flournoy, N; Rosenberger, W F

1997-06-01

We describe a family of random walk rules for the sequential allocation of dose levels to patients in a dose-response study, or phase I clinical trial. Patients are sequentially assigned the next higher, same, or next lower dose level according to some probability distribution, which may be determined by ethical considerations as well as the patient's response. It is shown that one can choose these probabilities in order to center dose level assignments unimodally around any target quantile of interest. Estimation of the quantile is discussed; the maximum likelihood estimator and its variance are derived under a two-parameter logistic distribution, and the maximum likelihood estimator is compared with other nonparametric estimators. Random walk rules have clear advantages: they are simple to implement, and finite and asymptotic distribution theory is completely worked out. For a specific random walk rule, we compute finite and asymptotic properties and give examples of its use in planning studies. Having the finite distribution theory available and tractable obviates the need for elaborate simulation studies to analyze the properties of the design. The small sample properties of our rule, as determined by exact theory, compare favorably to those of the continual reassessment method, determined by simulation.

A Randomized Controlled Trial of Consensus-Based Child Abuse Case Management

ERIC Educational Resources Information Center

Goldbeck, L.; Laib-Koehnemund, A.; Fegert, J. M.

2007-01-01

Objective: This study evaluates the effects of expert-assisted child abuse and neglect case management in the German child welfare and healthcare system as perceived by the case workers themselves. Methods: Case workers with different professions (social workers, counselors, clinic-based and office-based psychotherapists, and physicians)…

Human Papillomavirus Vaccine Intent and Uptake among Female College Students

ERIC Educational Resources Information Center

Patel, Divya A.; Zochowski, Melissa; Peterman, Stephanie; Dempsey, Amanda F.; Ernst, Susan; Dalton, Vanessa K.

2012-01-01

Objective: To examine human papillomavirus (HPV) vaccine intent and the effect of an educational intervention on vaccine uptake among female college students. Participants: Females aged 18 to 26 attending a university health service gynecology clinic (n = 256). Methods: Participants were randomized to receive either HPV-specific education with a…

Family Cognitive Behavioral Therapy for Child Anxiety Disorders

ERIC Educational Resources Information Center

Wood, Jeffrey J.; Piacentini, John C.; Southam-Gerow, Michael; Chu, Brian C.; Sigman, Marian

2006-01-01

Objective: This study compared family-focused cognitive behavioral therapy (CBT: the Building Confidence Program) with traditional child-focused CBT with minimal family involvement for children with anxiety disorders. Method: Forty clinically anxious youth (6-13 years old) were randomly assigned to a family- or child-focused cognitive-behavioral…

A Randomized Trial of Contingency Management Delivered by Community Therapists

ERIC Educational Resources Information Center

Petry, Nancy M.; Alessi, Sheila M.; Ledgerwood, David M.

2012-01-01

Objective: Contingency management (CM) is an evidence-based treatment, but few clinicians deliver this intervention in community-based settings. Method: Twenty-three clinicians from 3 methadone maintenance clinics received training in CM. Following a didactics seminar and a training and supervision period in which clinicians delivered CM to pilot…

Social Support, a Mediator in Collaborative Depression Care for Cancer Patients

ERIC Educational Resources Information Center

Oh, Hyunsung; Ell, Kathleen

2015-01-01

Objective: This study assessed whether perceived social support (PSS) is a factor in improving physical and functional well-being observed among cancer patients receiving collaborative depression care. Methods: A secondary analysis was conducted of data collected in a randomized clinical trial testing the effectiveness of collaborative depression…

Assessing the Generalizability of Randomized Trial Results to Target Populations

PubMed Central

Stuart, Elizabeth A.; Bradshaw, Catherine P.; Leaf, Philip J.

2014-01-01

Recent years have seen increasing interest in and attention to evidence-based practices, where the “evidence” generally comes from well-conducted randomized trials. However, while those trials yield accurate estimates of the effect of the intervention for the participants in the trial (known as “internal validity”), they do not always yield relevant information about the effects in a particular target population (known as “external validity”). This may be due to a lack of specification of a target population when designing the trial, difficulties recruiting a sample that is representative of a pre-specified target population, or to interest in considering a target population somewhat different from the population directly targeted by the trial. This paper first provides an overview of existing design and analysis methods for assessing and enhancing the ability of a randomized trial to estimate treatment effects in a target population. It then provides a case study using one particular method, which weights the subjects in a randomized trial to match the population on a set of observed characteristics. The case study uses data from a randomized trial of School-wide Positive Behavioral Interventions and Supports (PBIS); our interest is in generalizing the results to the state of Maryland. In the case of PBIS, after weighting, estimated effects in the target population were similar to those observed in the randomized trial. The paper illustrates that statistical methods can be used to assess and enhance the external validity of randomized trials, making the results more applicable to policy and clinical questions. However, there are also many open research questions; future research should focus on questions of treatment effect heterogeneity and further developing these methods for enhancing external validity. Researchers should think carefully about the external validity of randomized trials and be cautious about extrapolating results to specific populations unless they are confident of the similarity between the trial sample and that target population. PMID:25307417

Assessing the generalizability of randomized trial results to target populations.

PubMed

Stuart, Elizabeth A; Bradshaw, Catherine P; Leaf, Philip J

2015-04-01

Recent years have seen increasing interest in and attention to evidence-based practices, where the "evidence" generally comes from well-conducted randomized trials. However, while those trials yield accurate estimates of the effect of the intervention for the participants in the trial (known as "internal validity"), they do not always yield relevant information about the effects in a particular target population (known as "external validity"). This may be due to a lack of specification of a target population when designing the trial, difficulties recruiting a sample that is representative of a prespecified target population, or to interest in considering a target population somewhat different from the population directly targeted by the trial. This paper first provides an overview of existing design and analysis methods for assessing and enhancing the ability of a randomized trial to estimate treatment effects in a target population. It then provides a case study using one particular method, which weights the subjects in a randomized trial to match the population on a set of observed characteristics. The case study uses data from a randomized trial of school-wide positive behavioral interventions and supports (PBIS); our interest is in generalizing the results to the state of Maryland. In the case of PBIS, after weighting, estimated effects in the target population were similar to those observed in the randomized trial. The paper illustrates that statistical methods can be used to assess and enhance the external validity of randomized trials, making the results more applicable to policy and clinical questions. However, there are also many open research questions; future research should focus on questions of treatment effect heterogeneity and further developing these methods for enhancing external validity. Researchers should think carefully about the external validity of randomized trials and be cautious about extrapolating results to specific populations unless they are confident of the similarity between the trial sample and that target population.

Design and challenges for a randomized, multi-site clinical trial comparing the use of service dogs and emotional support dogs in Veterans with post-traumatic stress disorder (PTSD).

PubMed

Saunders, Gabrielle H; Biswas, Kousick; Serpi, Tracey; McGovern, Stephanie; Groer, Shirley; Stock, Eileen M; Magruder, Kathryn M; Storzbach, Daniel; Skelton, Kelly; Abrams, Thad; McCranie, Mark; Richerson, Joan; Dorn, Patricia A; Huang, Grant D; Fallon, Michael T

2017-11-01

Posttraumatic stress disorder (PTSD) is a leading cause of impairments in quality of life and functioning among Veterans. Service dogs have been promoted as an effective adjunctive intervention for PTSD, however published research is limited and design and implementation flaws in published studies limit validated conclusions. This paper describes the rationale for the study design, a detailed methodological description, and implementation challenges of a multisite randomized clinical trial examining the impact of service dogs on the on the functioning and quality of life of Veterans with PTSD. Trial design considerations prioritized participant and intervention (dog) safety, selection of an intervention comparison group that would optimize enrollment in all treatment arms, pragmatic methods to ensure healthy well-trained dogs, and the selection of outcomes for achieving scientific and clinical validity in a Veteran PTSD population. Since there is no blueprint for conducting a randomized clinical trial examining the impact of dogs on PTSD of this size and scope, it is our primary intent that the successful completion of this trial will set a benchmark for future trial design and scientific rigor, as well as guiding researchers aiming to better understand the role that dogs can have in the management of Veterans experiencing mental health conditions such as PTSD. Published by Elsevier Inc.

Whose data set is it anyway? Sharing raw data from randomized trials.

PubMed

Vickers, Andrew J

2006-05-16

Sharing of raw research data is common in many areas of medical research, genomics being perhaps the most well-known example. In the clinical trial community investigators routinely refuse to share raw data from a randomized trial without giving a reason. Data sharing benefits numerous research-related activities: reproducing analyses; testing secondary hypotheses; developing and evaluating novel statistical methods; teaching; aiding design of future trials; meta-analysis; and, possibly, preventing error, fraud and selective reporting. Clinical trialists, however, sometimes appear overly concerned with being scooped and with misrepresentation of their work. Both possibilities can be avoided with simple measures such as inclusion of the original trialists as co-authors on any publication resulting from data sharing. Moreover, if we treat any data set as belonging to the patients who comprise it, rather than the investigators, such concerns fall away. Technological developments, particularly the Internet, have made data sharing generally a trivial logistical problem. Data sharing should come to be seen as an inherent part of conducting a randomized trial, similar to the way in which we consider ethical review and publication of study results. Journals and funding bodies should insist that trialists make raw data available, for example, by publishing data on the Web. If the clinical trial community continues to fail with respect to data sharing, we will only strengthen the public perception that we do clinical trials to benefit ourselves, not our patients.

A protocol for a randomized clinical trial of interactive video dance: potential for effects on cognitive function

PubMed Central

2012-01-01

Background Physical exercise has the potential to affect cognitive function, but most evidence to date focuses on cognitive effects of fitness training. Cognitive exercise also may influence cognitive function, but many cognitive training paradigms have failed to provide carry-over to daily cognitive function. Video games provide a broader, more contextual approach to cognitive training that may induce cognitive gains and have carry over to daily function. Most video games do not involve physical exercise, but some novel forms of interactive video games combine physical activity and cognitive challenge. Methods/Design This paper describes a randomized clinical trial in 168 postmenopausal sedentary overweight women that compares an interactive video dance game with brisk walking and delayed entry controls. The primary endpoint is adherence to activity at six months. Additional endpoints include aspects of physical and mental health. We focus this report primarily on the rationale and plans for assessment of multiple cognitive functions. Discussion This randomized clinical trial may provide new information about the cognitive effects of interactive videodance. It is also the first trial to examine physical and cognitive effects in older women. Interactive video games may offer novel strategies to promote physical activity and health across the life span. The study is IRB approved and the number is: PRO08080012 ClinicalTrials.gov Identifier: NCT01443455 PMID:22672287

Feasibility, Acceptability and Findings from a Pilot Randomized Controlled Intervention Study on the Impact of a Book Designed to Inform Patients about Cancer Clinical Trials

PubMed Central

Carney, Patricia A.; Tucker, Erin K.; Newby, Timothy A.; Beer, Tomasz M.

2014-01-01

Objective To assess the feasibility, acceptability and changes in knowledge among cancer patients assigned to receive a 160 page book on experimental cancer therapies and clinical trials. Methods We enrolled 20 patients with cancer who had never participated in a clinical trial, and randomly assigned them to receive the book either during Week 1or Week 4 of the study. We collected baseline patient demographic and cancer related information as well as knowledge about cancer clinical trials at Week 0. Follow-up surveys were administered at Weeks 3 and 6 for both study groups. Comparisons were made within and between groups randomized to receive the book Early (at Week 1) to those who received it Later (at Week 4). Results One hundred percent of data were captured in both groups at baseline, which decreased to 77.8% by Week 6. The vast majority of participants found the book moderately or very useful (89% in the Early Group at Week 3 and 95.5% in the Late Group at Week 6). Within group pair-wise comparisons found significant difference between baseline and Week 6 in content-specific knowledge scores among participants in the Late Group (79% vs. 92.1%, p=0.01). Global knowledge scores increased significantly for variables reflecting knowledge that promotes decisions to participate in clinical trials. Conclusions Providing published reading material to patients with cancer is both feasible and acceptable. Offering information to patients about cancer clinical trials, using a book designed for patients with cancer may influence knowledge related to decision to participate in clinical trials. PMID:24127249

Strategies and Opportunities to STOP Colon Cancer in Priority Populations: design of a cluster-randomized pragmatic trial.

PubMed

Coronado, Gloria D; Vollmer, William M; Petrik, Amanda; Taplin, Stephen H; Burdick, Timothy E; Meenan, Richard T; Green, Beverly B

2014-07-01

Colorectal cancer is the second-leading cause of cancer deaths in the United States. The Strategies and Opportunities to Stop Colorectal Cancer (STOP CRC) in Priority Populations study is a pragmatic trial and a collaboration between two research institutions and a network of more than 200 safety net clinics. The study will assess the effectiveness of a system-based intervention designed to improve the rates of colorectal-cancer screening using fecal immunochemical testing (FIT) in federally qualified health centers in Oregon and Northern California. STOP CRC is a cluster-randomized comparative-effectiveness pragmatic trial enrolling 26 clinics. Clinics will be randomized to one of two arms. Clinics in the intervention arm (1) will use an automated, data-driven, electronic health record-embedded program to identify patients due for colorectal screening and mail FIT kits (with pictographic instructions) to them; (2) will conduct an improvement process (e.g. Plan-Do-Study-Act) to enhance the adoption, reach, and effectiveness of the program. Clinics in the control arm will provide opportunistic colorectal-cancer screening to patients at clinic visits. The primary outcomes are: proportion of age- and screening-eligible patients completing a FIT within 12months; and cost, cost-effectiveness, and return on investment of the intervention. This large-scale pragmatic trial will leverage electronic health record information and existing clinic staff to enroll a broad range of patients, including many with historically low colorectal-cancer screening rates. If successful, the program will provide a model for a cost-effective and scalable method to raise colorectal-cancer screening rates. Copyright © 2014 Elsevier Inc. All rights reserved.

Combining structured and unstructured data to identify a cohort of ICU patients who received dialysis

PubMed Central

Abhyankar, Swapna; Demner-Fushman, Dina; Callaghan, Fiona M; McDonald, Clement J

2014-01-01

Objective To develop a generalizable method for identifying patient cohorts from electronic health record (EHR) data—in this case, patients having dialysis—that uses simple information retrieval (IR) tools. Methods We used the coded data and clinical notes from the 24 506 adult patients in the Multiparameter Intelligent Monitoring in Intensive Care database to identify patients who had dialysis. We used SQL queries to search the procedure, diagnosis, and coded nursing observations tables based on ICD-9 and local codes. We used a domain-specific search engine to find clinical notes containing terms related to dialysis. We manually validated the available records for a 10% random sample of patients who potentially had dialysis and a random sample of 200 patients who were not identified as having dialysis based on any of the sources. Results We identified 1844 patients that potentially had dialysis: 1481 from the three coded sources and 1624 from the clinical notes. Precision for identifying dialysis patients based on available data was estimated to be 78.4% (95% CI 71.9% to 84.2%) and recall was 100% (95% CI 86% to 100%). Conclusions Combining structured EHR data with information from clinical notes using simple queries increases the utility of both types of data for cohort identification. Patients identified by more than one source are more likely to meet the inclusion criteria; however, including patients found in any of the sources increases recall. This method is attractive because it is available to researchers with access to EHR data and off-the-shelf IR tools. PMID:24384230

Proteomics Versus Clinical Data and Stochastic Local Search Based Feature Selection for Acute Myeloid Leukemia Patients' Classification.

PubMed

Chebouba, Lokmane; Boughaci, Dalila; Guziolowski, Carito

2018-06-04

The use of data issued from high throughput technologies in drug target problems is widely widespread during the last decades. This study proposes a meta-heuristic framework using stochastic local search (SLS) combined with random forest (RF) where the aim is to specify the most important genes and proteins leading to the best classification of Acute Myeloid Leukemia (AML) patients. First we use a stochastic local search meta-heuristic as a feature selection technique to select the most significant proteins to be used in the classification task step. Then we apply RF to classify new patients into their corresponding classes. The evaluation technique is to run the RF classifier on the training data to get a model. Then, we apply this model on the test data to find the appropriate class. We use as metrics the balanced accuracy (BAC) and the area under the receiver operating characteristic curve (AUROC) to measure the performance of our model. The proposed method is evaluated on the dataset issued from DREAM 9 challenge. The comparison is done with a pure random forest (without feature selection), and with the two best ranked results of the DREAM 9 challenge. We used three types of data: only clinical data, only proteomics data, and finally clinical and proteomics data combined. The numerical results show that the highest scores are obtained when using clinical data alone, and the lowest is obtained when using proteomics data alone. Further, our method succeeds in finding promising results compared to the methods presented in the DREAM challenge.

Stigma and Barriers to Care Caring for Those Exposed to War, Disaster and Terrorism

DTIC Science & Technology

2012-03-06

behaviors, and injury. There is a paucity of qualitative study of the narratives of injured soldiers who successfully negotiated barriers to care...Develop qualitative methods to examine the narratives of successful treat- ment across the trajectories of accessing care. • Examine technologies... study and randomize them." Thirty patients consented to this protocol. It is the application of ethnographic methods . It is clinical ethnography . We

Clinical trials in dentistry in India: Analysis from trial registry.

PubMed

Gowri, S; Kannan, Sridharan

2017-01-01

Evidence-based practice requires clinical trials to be performed. In India, if any clinical trial has to be performed, it has to be registered with clinical trial registry of India. Studies have shown that the report of clinical trials is poor in dentistry. Hence, the present study has been conducted to assess the type and trends of clinical trials being undertaken in dentistry in India over a span of 6 years. All the clinical trials which were registered with the Central Trial Registry of India (CTRI) (www.ctri.nic.in) from January 1, 2007 to March 3, 2014 were evaluated using the keyword "dental." Following information were collected for each of the clinical trials obtained from the search; number of centres (single center/multicentric), type of the institution undertaking the research (government/private/combined), study (observational/interventional), study design (randomized/single blinded/double-blinded), type of health condition, type of participants (healthy/patients), sponsors (academia/commercial), phase of clinical trial (Phase 1/2/3/4), publication details (published/not published), whether it was a postgraduate thesis or not and prospective or retrospective registration of clinical trials, methodological quality (method of randomization, allocation concealment). Descriptive statistics was used for analysis of various categories. Trend analysis was done to assess the changes over a period of time. The search yielded a total of 84 trials of which majority of them were single centered. Considering the study design more than half of the registered clinical trials were double-blinded (47/84 [56%]). With regard to the place of conducting a trial, most of the trials were planned to be performed in private hospitals (56/84 [66.7%]). Most (79/84, 94.1%) of the clinical trials were interventional while only 5/84 (5.9%) were observational. Majority (65/84, 77.4%) of the registered clinical trials were recruiting patients while the rest were being done in healthy participants. From 2011, some of the postgraduate thesis trials had also been registered (2011-8; 2012-8; 2013-13; 2014-6). Inadequacy in reporting the method of randomization and allocation concealment was observed in 37/67 (55.2%) and 31/67 (46.2%) clinical trials respectively. A considerable number of postgraduate theses was also registered with CTRI in dentistry and majority of the clinical trials despite being completed are not yet published. The number of clinical trials in dentistry are low in India, and more focus should be placed by dental investigators regarding the reporting standards. Furthermore, researchers and trial sponsors should aim at publication of the research findings so that it is made publically available for use. A clear-cut need exists for an increase in both the quantity and quality of clinical trials in dentistry.

The Effect of Virtual Reality on Pain in Primiparity Women during Episiotomy Repair: A Randomize Clinical Trial

PubMed Central

JahaniShoorab, Nahid; Ebrahimzadeh Zagami, Samira; Nahvi, Ali; Mazluom, Seyed Reza; Golmakani, Nahid; Talebi, Mahdi; Pabarja, Ferial

2015-01-01

Background Pain is one of the side effects of episiotomy. The virtual reality (VR) is a non-pharmacological method for pain relief. The purpose of this study was to determine the effect of using video glasses on pain reduction in primiparity women during episiotomy repair. Methods This clinical trial was conducted on 30 primiparous parturient women having labor at Omolbanin Hospital (Mashhad, Iran) during May-July 2012. Samples during episiotomy repair were randomly divided into two equal groups. The intervention group received the usual treatment with VR (video glasses and local infiltration 5 ml solution of lidocaine 2%) and the control group only received local infiltration (5 ml solution of lidocaine 2%). Pain was measured using the Numeric Pain Rating Scale (0-100 scale) before, during and after the episiotomy repair. Data were analyzed using Fisher’s exact test, Chi-square, Mann-Whitney and repeated measures ANOVA tests by SPSS 11.5 software. Results There were statistically significant differences between the pain score during episiotomy repair in both groups (P=0.038). Conclusion Virtual reality is an effective complementary non-pharmacological method to reduce pain during episiotomy repair. Trial Registration Number: IRCT138811063185N1. PMID:25999621

Tubal anastomosis after previous sterilization: a systematic review.

PubMed

van Seeters, Jacoba A H; Chua, Su Jen; Mol, Ben W J; Koks, Carolien A M

2017-05-01

Female sterilization is one of the most common contraceptive methods. A small number of women, however, opt for reversal of sterilization procedures after they experience regret. Procedures can be performed by laparotomy or laparoscopy, with or without robotic assistance. Another commonly utilized alternative is IVF. The choice between surgery and IVF is often influenced by reimbursement politics for that particular geographic location. We evaluated the fertility outcomes of different surgical methods available for the reversal of female sterilization, compared these to IVF and assessed the prognostic factors for success. Two search strategies were employed. Firstly, we searched for randomized and non-randomized clinical studies presenting fertility outcomes of sterilization reversal up to July 2016. Data on the following outcomes were collected: pregnancy rate, ectopic pregnancy rate, cost of the procedure and operative time. Eligible study designs included prospective or retrospective studies, randomized controlled trials, cohort studies, case-control studies and case series. No age restriction was applied. Exclusion criteria were patients suffering from tubal infertility from any other reason (e.g. infection, endometriosis and adhesions from previous surgery) and studies including <10 participants. The following factors likely to influence the success of sterilization reversal procedures were then evaluated: female age, BMI and duration and method of sterilization. Secondly, we searched for randomized and non-randomized clinical studies that compared reversal of sterilization to IVF and evaluated them for pregnancy outcomes and cost effectiveness. We included 37 studies that investigated a total of 10 689 women. No randomized controlled trials were found. Most studies were retrospective cohort studies of a moderate quality. The pooled pregnancy rate after sterilization reversal was 42-69%, with heterogeneity seen from the different methods utilized. The reported ectopic pregnancy rate was 4-8%. The only prognostic factor affecting the chance of conception was female age. The surgical approach (i.e. laparotomy [microscopic], laparoscopy or robotic) had no impact on the outcome, with the exception of the macroscopic laparotomic technique, which had inferior results and is not currently utilized. For older women, IVF could be a more cost-effective alternative for the reversal of sterilization. However, direct comparative data are lacking and a cut-off age cannot be stated. In sterilized women who suffer regret, surgical tubal re-anastomosis is an effective treatment, especially in younger women. However, there is a need for randomized controlled trials comparing the success rates and costs of surgical reversal with IVF. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Comparative effectiveness, safety and acceptability of medical abortion at home and in a clinic: a systematic review

PubMed Central

Park, Min Hae; Shakur, Haleema; Free, Caroline

2011-01-01

Abstract Objective To compare medical abortion practised at home and in clinics in terms of effectiveness, safety and acceptability. Methods A systematic search for randomized controlled trials and prospective cohort studies comparing home-based and clinic-based medical abortion was conducted. The Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE and Popline were searched. Failure to abort completely, side-effects and acceptability were the main outcomes of interest. Odds ratios and their 95% confidence intervals (CIs) were calculated. Estimates were pooled using a random-effects model. Findings Nine studies met the inclusion criteria (n = 4522 participants). All were prospective cohort studies that used mifepristone and misoprostol to induce abortion. Complete abortion was achieved by 86–97% of the women who underwent home-based abortion (n = 3478) and by 80–99% of those who underwent clinic-based abortion (n = 1044). Pooled analyses from all studies revealed no difference in complete abortion rates between groups (odds ratio = 0.8; 95% CI: 0.5–1.5). Serious complications from abortion were rare. Pain and vomiting lasted 0.3 days longer among women who took misoprostol at home rather than in clinic. Women who chose home-based medical abortion were more likely to be satisfied, to choose the method again and to recommend it to a friend than women who opted for medical abortion in a clinic. Conclusion Home-based abortion is safe under the conditions in place in the included studies. Prospective cohort studies have shown no differences in effectiveness or acceptability between home-based and clinic-based medical abortion across countries. PMID:21556304

Comparison of Transcutaneous Electrical Nerve Stimulation and Lidocaine on Episiotomy Complication in Primiparous Women: A Randomized Clinical Trial

PubMed Central

Rezaeyan, Maryam; Geranmayeh, Mehrnaz; Direkvand-Moghadam, Ashraf

2017-01-01

Introduction: Transcutaneous electrical nerve stimulation (TENS) through the skin is a nonpharmacological method of pain relief. The present study aimed to compare TENS and lidocaine on episiotomy complication in primiparous women. Material and Methods: In a randomized, controlled clinical trial, 80 participants were included from March to July 2011 at the antenatal clinic and postdelivery ward in the Social Security Organization Hospital, Khorramabad, Lorestan, Iran. Data were collected using a demographic questionnaire, visual analog scale and redness, edema, ecchymosis, discharge, and approximation scales. The participants were randomized into two groups with equal number of participants. All participants received 5 cc of local infiltration of 1% lidocaine before episiotomy, and TENS electrodes were placed on He Gu and Shenmen points during the crowning of fetal head. The TENS group received TENS with 100; 250 μs, the output range of 15–20 mm amplifier from crowning of first stage of labor to the end of the episiotomy repairing. The lidocaine group received 10 cc of local infiltration of 1% lidocaine before episiotomy repair while did not receive TENS electrodes. The pain intensity during and after episiotomy repair was recorded. Results: TENS and lidocaine have similar effects on pain relief at the episiotomy cutting, the start of the episiotomy repair, and at end of the episiotomy repair; however, the pain relief of both the interventions was different during the episiotomy repair. The effect of TENS in reducing edema was statistically significant (P = 0.001). Conclusions: TENS and lidocaine are effective for the episiotomy complications during and after episiotomy repair. PMID:28382054

Treatment of early-onset schizophrenia spectrum disorders (TEOSS): rationale, design, and methods.

PubMed

McClellan, Jon; Sikich, Linmarie; Findling, Robert L; Frazier, Jean A; Vitiello, Benedetto; Hlastala, Stefanie A; Williams, Emily; Ambler, Denisse; Hunt-Harrison, Tyehimba; Maloney, Ann E; Ritz, Louise; Anderson, Robert; Hamer, Robert M; Lieberman, Jeffrey A

2007-08-01

The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early Onset Schizophrenia Spectrum Disorders Study are described. Using a randomized, double-blind, parallel-group design at four sites, youths with EOSS (ages 8-19 years) were assigned to an 8-week acute trial of risperidone (0.5-6.0 mg/day), olanzapine (2.5-20 mg/day), or molindone (10-140 mg/day). Responders continued double-blind treatment for 44 weeks. The primary outcome measure was responder status at 8 weeks, defined by a 20% reduction in baseline Positive and Negative Symptom Scale scores plus ratings of significant improvement on the Clinical Global Impressions. Secondary outcome measures included assessments of psychopathology, functional impairment, quality of life, and medication safety. An intent-to-treat analytic plan was used. From February 2002 to May 2006, 476 youths were screened, 173 were further evaluated, and 119 were randomized. Several significant study modifications were required to address safety, the use of adjunctive medications, and the termination of the olanzapine treatment arm due to weight gain. The Treatment of Early Onset Schizophrenia Spectrum Disorders Study will inform clinical practice regarding the use of antipsychotic medications for youths with early-onset schizophrenia spectrum disorders. Important safety concerns emerged during the study, including higher than anticipated rates of suicidality and problems tapering thymoleptic agents before randomization.

Effect of Play-based Therapy on Meta-cognitive and Behavioral Aspects of Executive Function: A Randomized, Controlled, Clinical Trial on the Students With Learning Disabilities.

PubMed

Karamali Esmaili, Samaneh; Shafaroodi, Narges; Hassani Mehraban, Afsoon; Parand, Akram; Zarei, Masoume; Akbari-Zardkhaneh, Saeed

2017-01-01

Although the effect of educational methods on executive function (EF) is well known, training this function by a playful method is debatable. The current study aimed at investigating if a play-based intervention is effective on metacognitive and behavioral skills of EF in students with specific learning disabilities. In the current randomized, clinical trial, 49 subjects within the age range of 7 to 11 years with specific learning disabilities were randomly assigned into the intervention (25 subjects; mean age 8.5±1.33 years) and control (24 subjects; mean age 8.7±1.03 years) groups. Subjects in the intervention group received EF group training based on playing activities; subjects in the control group received no intervention. The behavior rating inventory of executive function (BRIEF) was administered to evaluate the behavioral and cognitive aspects of EF. The duration of the intervention was 6 hours per week for 9 weeks. Multivariate analysis of covariance was used to compare mean changes (before and after) in the BRIEF scores between the groups. The assumptions of multivariate analysis of covariance were examined. After controlling pre-test conditions, the intervention and control groups scored significantly differently on both the metacognition (P=0.002; effect size=0.20) and behavior regulation indices (P=0.01; effect size=0.12) of BRIEF. Play-based therapy is effective on the metacognitive and behavioral aspects of EF in students with specific learning disabilities. Professionals can use play-based therapy rather than educational approaches in clinical practice to enhance EF skills.

Feasibility of the Enhancing Participation In the Community by improving Wheelchair Skills (EPIC Wheels) program: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Many older adults rely on a manual wheelchair for mobility but typically receive little, if any, training on how to use their wheelchair effectively and independently. Standardized skill training is an effective intervention, but limited access to clinician trainers is a substantive barrier. Enhancing Participation in the Community by Improving Wheelchair Skills (EPIC Wheels) is a 1-month monitored home training program for improving mobility skills in older novice manual wheelchair users, integrating principles from andragogy and social cognitive theory. The purpose of this study is to determine whether feasibility indicators and primary clinical outcome measures of the EPIC Wheels program are sufficiently robust to justify conducting a subsequent multi-site randomized controlled trial. Methods A 2 × 2 factorial randomized controlled trial at two sites will compare improvement in wheelchair mobility skills between an EPIC Wheels treatment group and a computer-game control group, with additional wheelchair use introduced as a second factor. A total of 40 community-dwelling manual wheelchair users at least 55 years old and living in two Canadian metropolitan cities (n = 20 × 2) will be recruited. Feasibility indicators related to study process, resources, management, and treatment issues will be collected during data collection and at the end of the study period, and evaluated against proposed criteria. Clinical outcome measures will be collected at baseline (pre-randomization) and post-intervention. The primary clinical outcome measure is wheelchair skill capacity, as determined by the Wheelchair Skills Test, version 4.1. Secondary clinical outcome measures include wheelchair skill safety, satisfaction with performance, wheelchair confidence, life-space mobility, divided-attention, and health-related quality of life. Discussion The EPIC Wheels training program offers several innovative features. The convenient, portable, economical, and adaptable tablet-based, home program model for wheelchair skills training has great potential for clinical uptake and opportunity for future enhancements. Theory-driven design can foster learning and adherence for older adults. Establishing the feasibility of the study protocol and estimating effect size for the primary clinical outcome measure will be used to develop a multi-site randomized controlled trial to test the guiding hypotheses. Trial registration Clinical Trials NCT01740635. PMID:24156396

Treatment of varicocele: a prospective randomized comparison of laparoscopy versus antegrade sclerotherapy.

PubMed

Sautter, T; Sulser, T; Suter, St; Gretener, H; Hauri, D

2002-04-01

To compare the therapeutic success, the morbidity and the costs of antegrade sclerotherapy versus laparoscopic varicocelectomy. Seventy-six consecutive varicocele patients were randomly assigned to two treatment arms. Preoperative and 3 month postoperative sperm density, motility and morphology were analysed. The diagnosis of the varicocele was established clinically and with Doppler ultrasonography. Fifty-eight patients treated by either of the two methods were followed up. The recurrence rate increased progressively with the size of the varicocele in both groups. The postoperative incidence of complications particularly hydrocele formation was significantly higher in the laparoscopic group. The costs of the disposable material for laparoscopic varicocelectomy was twice as high as for sclerotherapy. Antegrade sclerotherapy is the less invasive treatment method of male varicocele with lower costs and better outcome and should therefore be the preferred treatment method for male varicocele.

Radiographic evaluation of BFX acetabular component position in dogs.

PubMed

Renwick, Alasdair; Gemmill, Toby; Pink, Jonathan; Brodbelt, David; McKee, Malcolm

2011-07-01

To assess the reliability of radiographic measurement of angle of lateral opening (ALO) and angle of version of BFX acetabular cups. In vitro radiographic study. BFX cups (24, 28, and 32 mm). Total hip replacement constructs (cups, 17 mm femoral head and a #7 CFX stem) were mounted on an inclinometer. Ventrodorsal radiographs were obtained with ALO varying between 21° and 70° and inclination set at 0°, 10°, 20°, and 30°. Radiographs were randomized using a random sequence generator. Three observers blinded to the radiograph order assessed ALO using 3 methods: (1) an ellipse method based on trigonometry; (2) using a measurement from the center of the femoral head to the truncated surface of the cup; (3) by visual estimation using a reference chart. Version was measured by assessing the ventral edge of the truncated surface. ALO methods 2 and 3 were accurate and precise to within 10° and were significantly more accurate and precise than method 1 (P < .001). All methods were significantly less accurate with increasing inclination. Version measurement was accurate and precise to within 7° with 0-20° of inclination, but significantly less accurate with 30° of inclination. Methods 2 and 3, but not method 1, were sufficiently accurate and precise to be clinically useful. Version measurement was clinically useful when inclination was ≤ 20°. © Copyright 2011 by The American College of Veterinary Surgeons.

From Nonclinical Research to Clinical Trials and Patient-registries: Challenges and Opportunities in Biomedical Research

PubMed Central

de la Torre Hernández, José M.; Edelman, Elazer R.

2018-01-01

The most important challenge faced by human beings is health. The only way to provide better solutions for health care is innovation, true innovation. The only source of true innovation is research, good research indeed. The pathway from a basic science study to a randomized clinical trial is long and not free of bumps and even landmines. These are all the obstacles and barriers that limit the availability of resources, entangle administrative-regulatory processes, and restrain investigators’ initiatives. There is increasing demand for evidence to guide clinical practice but, paradoxically, biomedical research has become increasingly complex, expensive, and difficult to integrate into clinical care with increased barriers to performing the practical aspects of investigation. We face the challenge of increasing the volume of biomedical research and simultaneously improving the efficiency and output of this research. In this article, we review the main stages and methods of biomedical research, from nonclinical studies with animal and computational models to randomized trials and clinical registries, focusing on their limitations and challenges, but also providing alternative solutions to overcome them. Fortunately, challenges are always opportunities in disguise. PMID:28838647

Designs and adaptive analysis plans for pivotal clinical trials of therapeutics and companion diagnostics.

PubMed

Simon, Richard

2008-06-01

Developments in genomics and biotechnology provide unprecedented opportunities for the development of effective therapeutics and companion diagnostics for matching the right drug to the right patient. Effective co-development involves many new challenges with increased opportunity for success as well as delay and failure. Clinical trial designs and adaptive analysis plans for the prospective design of pivotal trials of new therapeutics and companion diagnostics are reviewed. Effective co-development requires careful prospective planning of the design and analysis strategy for pivotal clinical trials. Randomized clinical trials continue to be important for evaluating the effectiveness of new treatments, but the target populations for analysis should be prospectively specified based on the companion diagnostic. Post hoc analyses of traditionally designed randomized clinical trials are often deeply problematic. Clear separation is generally required of the data used for developing the diagnostic test, including their threshold of positivity, from the data used for evaluating treatment effectiveness in subsets determined by the test. Adaptive analysis can be used to provide flexibility to the analysis but the use of such methods requires careful planning and prospective definition in order to assure that the pivotal trial adequately limits the chance of erroneous conclusions.

The clinical application of teaching people about pain.

PubMed

Louw, Adriaan; Zimney, Kory; O'Hotto, Christine; Hilton, Sandra

2016-07-01

Teaching people about the neurobiology and neurophysiology of their pain experience has a therapeutic effect and has been referred to as pain neuroscience education (PNE). Various high-quality randomized controlled trials and systematic reviews have shown increasing efficacy of PNE decreasing pain, disability, pain catastrophization, movement restrictions, and healthcare utilization. Research studies, however, by virtue of their design, are very controlled environments and, therefore, in contrast to the ever-increasing evidence for PNE, little is known about the clinical application of this emerging therapy. In contrast, case studies, case series, and expert opinion and perspectives by authorities in the world of pain science provide clinicians with a glimpse into potential "real" clinical application of PNE in the face of the ever-increasing chronic pain epidemic. By taking the material from the randomized controlled trials, systematic reviews, case series, case studies, and expert opinion, this article aims to provide a proposed layout of the clinical application of PNE. The article systematically discusses key elements of PNE including examination, educational content, and delivery methods, merging of PNE with movement, goal setting, and progression. This perspectives article concludes with a call for research into the clinical application of PNE.

Medicine Based Evidence for Individualized Decision Making: Case Study of Systemic Lupus Erythematosus.

PubMed

Wivel, Ashley E; Lapane, Kate; Kleoudis, Christi; Singer, Burton H; Horwitz, Ralph I

2017-11-01

To guide management decisions for an index patient, evidence is required from comparisons between approximate matches to the profile of the index case, where some matches contain responses to treatment and others act as controls. We describe a method for constructing clinically relevant histories/profiles using data collected but unreported from 2 recent phase 3 randomized controlled trials assessing belimumab in subjects with clinically active and serologically positive systemic lupus erythematosus. Outcome was the Systemic lupus erythematosus Responder Index (SRI) measured at 52 weeks. Among 1175 subjects, we constructed an algorithm utilizing 11 trajectory variables including 4 biological, 2 clinical, and 5 social/behavioral. Across all biological and social/behavioral variables, the proportion of responders based on the SRI whose value indicated clinical worsening or no improvement ranged from 27.5% to 42.3%. Kappa values suggested poor agreement, indicating that each biological and patient-reported outcome provides different information than gleaned from the SRI. The richly detailed patient profiles needed to guide decision-making in clinical practice are sharply at odds with the limited information utilized in conventional randomized controlled trial analyses. Copyright © 2017 Elsevier Inc. All rights reserved.

Self-Management and Clinical Decision Support for Patients With Complex Chronic Conditions Through the Use of Smartphone-Based Telemonitoring: Randomized Controlled Trial Protocol

PubMed Central

Ware, Patrick; Logan, Alexander G; Cafazzo, Joseph A; Chapman, Kenneth R; Segal, Phillip; Ross, Heather J

2017-01-01

Background The rising prevalence of chronic illnesses hinders the sustainability of the health care system because of the high cost of frequent hospitalizations of patients with complex chronic conditions. Clinical trials have demonstrated that telemonitoring can improve health outcomes, but they have generally been limited to single conditions such as diabetes, hypertension, or heart failure. Few studies have examined the impact of telemonitoring on complex patients with multiple chronic conditions, although these patients may benefit the most from this technology. Objective The aim of this study is to investigate the impact of a smartphone-based telemonitoring system on the clinical care and health outcomes of complex patients across several chronic conditions. Methods A mixed-methods, 6-month randomized controlled trial (RCT) of a smartphone-based telemonitoring system is being conducted in specialty clinics. The study will include patients who have been diagnosed with one or more of any of the following conditions: heart failure, chronic obstructive pulmonary disease, chronic kidney disease, uncontrolled hypertension, or insulin-requiring diabetes. The primary outcome will be the health status of patients as measured with SF-36. Patients will be randomly assigned to either the control group receiving usual care (n=73) or the group using the smartphone-based telemonitoring system in addition to usual care (n=73). Results Participants are currently being recruited for the trial. Data collection is anticipated to be completed by the fall of 2018. Conclusions This RCT will be among the first trials to provide evidence of the impact of telemonitoring on costs and health outcomes of complex patients who may have multiple chronic conditions. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 41238563; http://www.isrctn.com/ISRCTN41238563 (Archived by WebCite at http://www.webcitation.org/6ug2Sk0af) and Clinicaltrials.gov NCT03127852; https://clinicaltrials.gov/ct2/show/NCT03127852 (Archived by WebCite at http://www.webcitation.org/6uvjNosBC) PMID:29162557

Progressive sampling-based Bayesian optimization for efficient and automatic machine learning model selection.

PubMed

Zeng, Xueqiang; Luo, Gang

2017-12-01

Machine learning is broadly used for clinical data analysis. Before training a model, a machine learning algorithm must be selected. Also, the values of one or more model parameters termed hyper-parameters must be set. Selecting algorithms and hyper-parameter values requires advanced machine learning knowledge and many labor-intensive manual iterations. To lower the bar to machine learning, miscellaneous automatic selection methods for algorithms and/or hyper-parameter values have been proposed. Existing automatic selection methods are inefficient on large data sets. This poses a challenge for using machine learning in the clinical big data era. To address the challenge, this paper presents progressive sampling-based Bayesian optimization, an efficient and automatic selection method for both algorithms and hyper-parameter values. We report an implementation of the method. We show that compared to a state of the art automatic selection method, our method can significantly reduce search time, classification error rate, and standard deviation of error rate due to randomization. This is major progress towards enabling fast turnaround in identifying high-quality solutions required by many machine learning-based clinical data analysis tasks.

Improved sampling and analysis of images in corneal confocal microscopy.

PubMed

Schaldemose, E L; Fontain, F I; Karlsson, P; Nyengaard, J R

2017-10-01

Corneal confocal microscopy (CCM) is a noninvasive clinical method to analyse and quantify corneal nerve fibres in vivo. Although the CCM technique is in constant progress, there are methodological limitations in terms of sampling of images and objectivity of the nerve quantification. The aim of this study was to present a randomized sampling method of the CCM images and to develop an adjusted area-dependent image analysis. Furthermore, a manual nerve fibre analysis method was compared to a fully automated method. 23 idiopathic small-fibre neuropathy patients were investigated using CCM. Corneal nerve fibre length density (CNFL) and corneal nerve fibre branch density (CNBD) were determined in both a manual and automatic manner. Differences in CNFL and CNBD between (1) the randomized and the most common sampling method, (2) the adjusted and the unadjusted area and (3) the manual and automated quantification method were investigated. The CNFL values were significantly lower when using the randomized sampling method compared to the most common method (p = 0.01). There was not a statistical significant difference in the CNBD values between the randomized and the most common sampling method (p = 0.85). CNFL and CNBD values were increased when using the adjusted area compared to the standard area. Additionally, the study found a significant increase in the CNFL and CNBD values when using the manual method compared to the automatic method (p ≤ 0.001). The study demonstrated a significant difference in the CNFL values between the randomized and common sampling method indicating the importance of clear guidelines for the image sampling. The increase in CNFL and CNBD values when using the adjusted cornea area is not surprising. The observed increases in both CNFL and CNBD values when using the manual method of nerve quantification compared to the automatic method are consistent with earlier findings. This study underlines the importance of improving the analysis of the CCM images in order to obtain more objective corneal nerve fibre measurements. © 2017 The Authors Journal of Microscopy © 2017 Royal Microscopical Society.

Follow-up of solar lentigo depigmentation with a retinaldehyde-based cream by clinical evaluation and calibrated colour imaging.

PubMed

Questel, E; Durbise, E; Bardy, A-L; Schmitt, A-M; Josse, G

2015-05-01

To assess an objective method evaluating the effects of a retinaldehyde-based cream (RA-cream) on solar lentigines; 29 women randomly applied RA-cream on lentigines of one hand and a control cream on the other, once daily for 3 months. A specific method enabling a reliable visualisation of the lesions was proposed, using high-magnification colour-calibrated camera imaging. Assessment was performed using clinical evaluation by Physician Global Assessment score and image analysis. Luminance determination on the numeric images was performed either on the basis of 5 independent expert's consensus borders or probability map analysis via an algorithm automatically detecting the pigmented area. Both image analysis methods showed a similar lightening of ΔL* = 2 after a 3-month treatment by RA-cream, in agreement with single-blind clinical evaluation. High-magnification colour-calibrated camera imaging combined with probability map analysis is a fast and precise method to follow lentigo depigmentation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Modality of combined methods of quantitative and qualitative research in evaluation of therapeutic effects of Chinese medicine].

PubMed

Liu, Jian-ping

2011-05-01

The core of evidence-based medicine lies in implementing the current best available evidence of clinical research to direct the decision making in clinical practice, incorporation of individual experience and value and preference of patients. However, the current evaluation method for clinical therapeutic effect cannot reflect the humanity and wholesomeness as well as individualized tailored treatment of Chinese medicine (CM) by using randomized controlled trials. This assay addressed the complex intervention of highly individualized treatment of CM and its societal characteristics, and the author proposes a model for the evaluation of therapeutic effects of CM in which quantitative and qualitative methods are combined, embodying the characteristics of the social and natural sciences in CM. The model can show the dynamic process of CM diagnosis and treatment from a perspective of the whole system and can be used for the evaluation of complex intervention of CM. We hope to raise a different thinking and method from the new drug development in the therapeutic effect evaluation.

Strategies for Dealing with Missing Data in Clinical Trials: From Design to Analysis

PubMed Central

Dziura, James D.; Post, Lori A.; Zhao, Qing; Fu, Zhixuan; Peduzzi, Peter

2013-01-01

Randomized clinical trials are the gold standard for evaluating interventions as randomized assignment equalizes known and unknown characteristics between intervention groups. However, when participants miss visits, the ability to conduct an intent-to-treat analysis and draw conclusions about a causal link is compromised. As guidance to those performing clinical trials, this review is a non-technical overview of the consequences of missing data and a prescription for its treatment beyond the typical analytic approaches to the entire research process. Examples of bias from incorrect analysis with missing data and discussion of the advantages/disadvantages of analytic methods are given. As no single analysis is definitive when missing data occurs, strategies for its prevention throughout the course of a trial are presented. We aim to convey an appreciation for how missing data influences results and an understanding of the need for careful consideration of missing data during the design, planning, conduct, and analytic stages. PMID:24058309

Fallibility: a new perspective on the ethics of clinical trial enrollment.

PubMed

Shamy, Michel C F; Stahnisch, Frank W; Hill, Michael D

2015-01-01

The ethical principle of 'equipoise', introduced in 1974, represents the most widely influential justification for the enrollment of patients into randomized clinical trials. However, definitions of equipoise vary, and its terms are not universally accepted. In this paper, we suggest a new way of approaching the ethics of clinical trial enrollment, which we call fallibility. The principle of fallibility argues that all physician opinions are sufficiently uncertain to warrant investigation, and that the ethical justification for any trial becomes a question of its epistemic validity, by which we mean the strength of its hypotheses and methods. The principle of fallibility can be translated into practice through the virtues of humility, skepticism and caring. While we cite recent examples from stroke medicine to demonstrate the limitations of equipoise, we propose that fallibility may offer a more general means of addressing the controversies that arise surrounding randomized controlled trials in many disciplines of medicine. © 2014 World Stroke Organization.

Collaborative Care for Older Adults with low back pain by family medicine physicians and doctors of chiropractic (COCOA): study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Low back pain is a prevalent and debilitating condition that affects the health and quality of life of older adults. Older people often consult primary care physicians about back pain, with many also receiving concurrent care from complementary and alternative medicine providers, most commonly doctors of chiropractic. However, a collaborative model of treatment coordination between these two provider groups has yet to be tested. The primary aim of the Collaborative Care for Older Adults Clinical Trial is to develop and evaluate the clinical effectiveness and feasibility of a patient-centered, collaborative care model with family medicine physicians and doctors of chiropractic for the treatment of low back pain in older adults. Methods/design This pragmatic, pilot randomized controlled trial will enroll 120 participants, age 65 years or older with subacute or chronic low back pain lasting at least one month, from a community-based sample in the Quad-Cities, Iowa/Illinois, USA. Eligible participants are allocated in a 1:1:1 ratio to receive 12 weeks of medical care, concurrent medical and chiropractic care, or collaborative medical and chiropractic care. Primary outcomes are self-rated back pain and disability. Secondary outcomes include general and functional health status, symptom bothersomeness, expectations for treatment effectiveness and improvement, fear avoidance behaviors, depression, anxiety, satisfaction, medication use and health care utilization. Treatment safety and adverse events also are monitored. Participant-rated outcome measures are collected via self-reported questionnaires and computer-assisted telephone interviews at baseline, and at 4, 8, 12, 24, 36 and 52 weeks post-randomization. Provider-rated expectations for treatment effectiveness and participant improvement also are evaluated. Process outcomes are assessed through qualitative interviews with study participants and research clinicians, chart audits of progress notes and content analysis of clinical trial notes. Discussion This pragmatic, pilot randomized controlled trial uses a mixed method approach to evaluate the clinical effectiveness, feasibility, and participant and provider perceptions of collaborative care between medical doctors and doctors of chiropractic in the treatment of older adults with low back pain. Trial registration This trial registered in ClinicalTrials.gov on 04 March 2011 with the ID number of NCT01312233. PMID:23324133

Comparison of non-surgical treatment methods for patients with lumbar spinal stenosis: protocol for a randomized controlled trial.

PubMed

Schneider, Michael; Ammendolia, Carlo; Murphy, Donald; Glick, Ronald; Piva, Sara; Hile, Elizabeth; Tudorascu, Dana; Morton, Sally C

2014-01-01

Lumbar spinal stenosis is the most common reason for spinal surgery in older adults. Previous studies have shown that surgery is effective for severe cases of stenosis, but many patients with mild to moderate symptoms are not surgical candidates. These patients and their providers are seeking effective non-surgical treatment methods to manage their symptoms; yet there is a paucity of comparative effectiveness research in this area. This knowledge gap has hindered the development of clinical practice guidelines for non-surgical treatment approaches for lumbar spinal stenosis. This study is a prospective randomized controlled clinical trial that will be conducted from November 2013 through October 2016. The sample will consist of 180 older adults (>60 years) who have both an anatomic diagnosis of stenosis confirmed by diagnostic imaging, and signs/symptoms consistent with a clinical diagnosis of lumbar spinal stenosis confirmed by clinical examination. Eligible subjects will be randomized into one of three pragmatic treatment groups: 1) usual medical care; 2) individualized manual therapy and rehabilitative exercise; or 3) community-based group exercise. All subjects will be treated for a 6-week course of care. The primary subjective outcome is the Swiss Spinal Stenosis Questionnaire, a self-reported measure of pain/function. The primary objective outcome is the Self-Paced Walking Test, a measure of walking capacity. The secondary objective outcome will be a measurement of physical activity during activities of daily living, using the SenseWear Armband, a portable device to be worn on the upper arm for one week. The primary analysis will use linear mixed models to compare the main effects of each treatment group on the changes in each outcome measure. Secondary analyses will include a responder analysis by group and an exploratory analysis of potential baseline predictors of treatment outcome. Our study should provide evidence that helps to inform patients and providers about the clinical benefits of three non-surgical approaches to the management of lumbar spinal stenosis symptoms. ClinicalTrials.gov identifier: NCT01943435.

Does mode of follow-up influence contraceptive use after medical abortion in a low-resource setting? Secondary outcome analysis of a non-inferiority randomized controlled trial.

PubMed

Paul, Mandira; Iyengar, Sharad D; Essén, Birgitta; Gemzell-Danielsson, Kristina; Iyengar, Kirti; Bring, Johan; Klingberg-Allvin, Marie

2016-10-17

Post-abortion contraceptive use in India is low and the use of modern methods of contraception is rare, especially in rural areas. This study primarily compares contraceptive use among women whose abortion outcome was assessed in-clinic with women who assessed their abortion outcome at home, in a low-resource, primary health care setting. Moreover, it investigates how background characteristics and abortion service provision influences contraceptive use post-abortion. A randomized controlled, non-inferiority, trial (RCT) compared clinic follow-up with home-assessment of abortion outcome at 2 weeks post-abortion. Additionally, contraceptive-use at 3 months post-abortion was investigated through a cross-sectional follow-up interview with a largely urban sub-sample of women from the RCT. Women seeking abortion with a gestational age of up to 9 weeks and who agreed to a 2-week follow-up were included (n = 731). Women with known contraindications to medical abortions, Hb < 85 mg/l and aged below 18 were excluded. Data were collected between April 2013 and August 2014 in six primary health-care clinics in Rajasthan. A computerised random number generator created the randomisation sequence (1:1) in blocks of six. Contraceptive use was measured at 2 weeks among women successfully followed-up (n = 623) and 3 months in the sub-set of women who were included if they were recruited at one of the urban study sites, owned a phone and agreed to a 3-month follow-up (n = 114). There were no differences between contraceptive use and continuation between study groups at 3 months (76 % clinic follow-up, 77 % home-assessment), however women in the clinic follow-up group were most likely to adopt a contraceptive method at 2 weeks (62 ± 12 %), while women in the home-assessment group were most likely to adopt a method after next menstruation (60 ± 13 %). Fifty-two per cent of women who initiated a method at 2 weeks chose the 3-month injection or the copper intrauterine device. Only 4 % of women preferred sterilization. Caste, educational attainment, or type of residence did not influence contraceptive use. Simplified follow-up after early medical abortion will not change women's opportunities to access contraception in a low-resource setting, if contraceptive services are provided as intra-abortion services as early as on day one. Women's postabortion contraceptive use at 3 months is unlikely to be affected by mode of followup after medical abortion, also in a low-resource setting. Clinical guidelines need to encourage intra-abortion contraception, offering the full spectrum of evidence-based methods, especially long-acting reversible methods. Clinicaltrials.gov NCT01827995.

Empirical likelihood inference in randomized clinical trials.

PubMed

Zhang, Biao

2017-01-01

In individually randomized controlled trials, in addition to the primary outcome, information is often available on a number of covariates prior to randomization. This information is frequently utilized to undertake adjustment for baseline characteristics in order to increase precision of the estimation of average treatment effects; such adjustment is usually performed via covariate adjustment in outcome regression models. Although the use of covariate adjustment is widely seen as desirable for making treatment effect estimates more precise and the corresponding hypothesis tests more powerful, there are considerable concerns that objective inference in randomized clinical trials can potentially be compromised. In this paper, we study an empirical likelihood approach to covariate adjustment and propose two unbiased estimating functions that automatically decouple evaluation of average treatment effects from regression modeling of covariate-outcome relationships. The resulting empirical likelihood estimator of the average treatment effect is as efficient as the existing efficient adjusted estimators 1 when separate treatment-specific working regression models are correctly specified, yet are at least as efficient as the existing efficient adjusted estimators 1 for any given treatment-specific working regression models whether or not they coincide with the true treatment-specific covariate-outcome relationships. We present a simulation study to compare the finite sample performance of various methods along with some results on analysis of a data set from an HIV clinical trial. The simulation results indicate that the proposed empirical likelihood approach is more efficient and powerful than its competitors when the working covariate-outcome relationships by treatment status are misspecified.

Characteristics of children and young adults with Marfan syndrome and aortic root dilation in a randomized trial comparing atenolol and losartan therapy

PubMed Central

Lacro, Ronald V.; Guey, Lin T.; Dietz, Harry C.; Pearson, Gail D.; Yetman, Anji T.; Gelb, Bruce D.; Loeys, Bart L.; Benson, D. Woodrow; Bradley, Timothy J.; De Backer, Julie; Forbus, Geoffrey A.; Klein, Gloria L.; Lai, Wyman W.; Levine, Jami C.; Lewin, Mark B.; Markham, Larry W.; Paridon, Stephen M.; Pierpont, Mary Ella; Radojewski, Elizabeth; Selamet Tierney, Elif Seda; Sharkey, Angela M.; Wechsler, Stephanie Burns; Mahony, Lynn

2013-01-01

Background The Pediatric Heart Network designed a clinical trial to compare aortic root growth and other short-term cardiovascular outcomes in children and young adults with Marfan syndrome randomized to receive atenolol or losartan. We report here the characteristics of the screened population and enrolled subjects. Methods and results Between 2007 and 2011, 21 clinical sites randomized 608 subjects, aged 6 months to 25 years who met the original Ghent criteria and had a body surface area–adjusted aortic root diameter z-score >3.0. The mean age at study entry was 11.2 years, 60% were male, and 25% were older teenagers and young adults. The median aortic root diameter z-score was 4.0. Aortic root diameter z-score did not vary with age. Mitral valve prolapse and mitral regurgitation were more common in females. Among those with a positive family history, 56% had a family member with aortic surgery, and 32% had a family member with a history of aortic dissection. Conclusions Baseline demographic, clinical, and anthropometric characteristics of the randomized cohort are representative of patients in this population with moderate to severe aortic root dilation. The high percentage of young subjects with relatives who have had aortic dissection or surgery illustrates the need for more definitive therapy; we expect that the results of the study and the wealth of systematic data collected will make an important contribution to the management of individuals with Marfan syndrome. PMID:23622922

Update to the study protocol, including statistical analysis plan for a randomized clinical trial comparing comprehensive cardiac rehabilitation after heart valve surgery with control: the CopenHeartVR trial.

PubMed

Sibilitz, Kirstine Laerum; Berg, Selina Kikkenborg; Hansen, Tina Birgitte; Risom, Signe Stelling; Rasmussen, Trine Bernholdt; Hassager, Christian; Køber, Lars; Gluud, Christian; Thygesen, Lau Caspar; Lindschou, Jane; Schmid, Jean Paul; Taylor, Rod S; Zwisler, Ann-Dorthe

2015-02-05

Heart valve diseases are common with an estimated prevalence of 2.5% in the Western world. The number is rising because of an ageing population. Once symptomatic, heart valve diseases are potentially lethal, and heavily influence daily living and quality of life. Surgical treatment, either valve replacement or repair, remains the treatment of choice. However, post-surgery, the transition to daily living may become a physical, mental and social challenge. We hypothesize that a comprehensive cardiac rehabilitation program can improve physical capacity and self-assessed mental health and reduce hospitalization and healthcare costs after heart valve surgery. This randomized clinical trial, CopenHeartVR, aims to investigate whether cardiac rehabilitation in addition to usual care is superior to treatment as usual after heart valve surgery. The trial will randomly allocate 210 patients 1:1 to an intervention or a control group, using central randomization, and blinded outcome assessment and statistical analyses. The intervention consists of 12 weeks of physical exercise and a psycho-educational intervention comprising five consultations. The primary outcome is peak oxygen uptake (VO2 peak) measured by cardiopulmonary exercise testing with ventilatory gas analysis. The secondary outcome is self-assessed mental health measured by the standardized questionnaire Short Form-36. Long-term healthcare utilization and mortality as well as biochemistry, echocardiography and cost-benefit will be assessed. A mixed-method design will be used to evaluate qualitative and quantitative findings, encompassing a survey-based study before the trial and a qualitative pre- and post-intervention study. This randomized clinical trial will contribute with evidence of whether cardiac rehabilitation should be provided after heart valve surgery. The study is approved by the local regional Research Ethics Committee (H-1-2011-157), and the Danish Data Protection Agency (j.nr. 2007-58-0015). Trial registered 16 March 2012; ClinicalTrials.gov ( NCT01558765 ).

SU-D-201-06: Random Walk Algorithm Seed Localization Parameters in Lung Positron Emission Tomography (PET) Images

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

Soufi, M; Asl, A Kamali; Geramifar, P

2015-06-15

Purpose: The objective of this study was to find the best seed localization parameters in random walk algorithm application to lung tumor delineation in Positron Emission Tomography (PET) images. Methods: PET images suffer from statistical noise and therefore tumor delineation in these images is a challenging task. Random walk algorithm, a graph based image segmentation technique, has reliable image noise robustness. Also its fast computation and fast editing characteristics make it powerful for clinical purposes. We implemented the random walk algorithm using MATLAB codes. The validation and verification of the algorithm have been done by 4D-NCAT phantom with spherical lungmore » lesions in different diameters from 20 to 90 mm (with incremental steps of 10 mm) and different tumor to background ratios of 4:1 and 8:1. STIR (Software for Tomographic Image Reconstruction) has been applied to reconstruct the phantom PET images with different pixel sizes of 2×2×2 and 4×4×4 mm{sup 3}. For seed localization, we selected pixels with different maximum Standardized Uptake Value (SUVmax) percentages, at least (70%, 80%, 90% and 100%) SUVmax for foreground seeds and up to (20% to 55%, 5% increment) SUVmax for background seeds. Also, for investigation of algorithm performance on clinical data, 19 patients with lung tumor were studied. The resulted contours from algorithm have been compared with nuclear medicine expert manual contouring as ground truth. Results: Phantom and clinical lesion segmentation have shown that the best segmentation results obtained by selecting the pixels with at least 70% SUVmax as foreground seeds and pixels up to 30% SUVmax as background seeds respectively. The mean Dice Similarity Coefficient of 94% ± 5% (83% ± 6%) and mean Hausdorff Distance of 1 (2) pixels have been obtained for phantom (clinical) study. Conclusion: The accurate results of random walk algorithm in PET image segmentation assure its application for radiation treatment planning and diagnosis.« less

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

Methodological Overview of an African American Couple-Based HIV/STD Prevention Trial

PubMed Central

2010-01-01

Objective To provide an overview of the NIMH Multisite HIV/STD Prevention Trial for African American Couples conducted in four urban areas: Atlanta, Los Angeles, New York, and Philadelphia. The rationale, study design methods, proposed data analyses, and study management are described. Design This is a two arm randomized Trial, implementing a modified randomized block design, to evaluate the efficacy of a couples based intervention designed for HIV serodiscordant African American couples. Methods The study phases consisted of formative work, pilot studies, and a randomized clinical trial. The sample is 535 HIV serodiscordant heterosexual African American couples. There are two theoretically derived behavioral interventions with eight group and individual sessions: the Eban HIV/STD Risk Reduction Intervention (treatment) versus the Eban Health Promotion Intervention (control). The treatment intervention was couples based and focused on HIV/STD risk reduction while the control was individual based and focused on health promotion. The two study conditions were structurally similar in length and types of activities. At baseline, participants completed an Audio Computer-assisted Self Interview (ACASI) interview as well as interviewer-administered questionnaire, and provided biological specimens to assess for STDs. Similar follow-up assessments were conducted immediately after the intervention, at 6 months, and at 12 months. Results The Trial results will be analyzed across the four sites by randomization assignment. Generalized estimating equations (GEE) and mixed effects modeling (MEM) are planned to test: (1) the effects of the intervention on STD incidence and condom use as well as on mediator variables of these outcomes, and (2) whether the effects of the intervention differ depending on key moderator variables (e.g., gender of the HIV-seropositive partners, length of relationship, psychological distress, sexual abuse history, and substance abuse history). Conclusions The lessons learned from the design and conduct of this clinical trial provide guidelines for future couples based clinical trials in HIV/STD risk reduction and can be generalized to other couples based behavioral interventions. PMID:18724188

A Randomized Trial Comparing Didactics, Demonstration, and Simulation for Teaching Teamwork to Medical Residents

PubMed Central

Keriwala, Raj D.; Clune, Jennifer K.; Rice, Todd W.; Pugh, Meredith E.; Wheeler, Arthur P.; Miller, Alison N.; Banerjee, Arna; Terhune, Kyla; Bastarache, Julie A.

2015-01-01

Rationale: Effective teamwork is fundamental to the management of medical emergencies, and yet the best method to teach teamwork skills to trainees remains unknown. Objectives: In a cohort of incoming internal medicine interns, we tested the hypothesis that expert demonstration of teamwork principles and participation in high-fidelity simulation would each result in objectively assessed teamwork behavior superior to traditional didactics. Methods: This was a randomized, controlled, parallel-group trial comparing three teamwork teaching modalities for incoming internal medicine interns. Participants in a single-day orientation at the Vanderbilt University Center for Experiential Learning and Assessment were randomized 1:1:1 to didactic, demonstration-based, or simulation-based instruction and then evaluated in their management of a simulated crisis by five independent, blinded observers using the Teamwork Behavioral Rater score. Clinical performance was assessed using the American Heart Association Advanced Cardiac Life Support algorithm and a novel “Recognize, Respond, Reassess” score. Measurements and Main Results: Participants randomized to didactics (n = 18), demonstration (n = 17), and simulation (n = 17) were similar at baseline. The primary outcome of average overall Teamwork Behavioral Rater score for those who received demonstration-based training was similar to simulation participation (4.40 ± 1.15 vs. 4.10 ± 0.95, P = 0.917) and significantly higher than didactic instruction (4.40 ± 1.15 vs. 3.10 ± 0.51, P = 0.045). Clinical performance scores were similar between the three groups and correlated only weakly with teamwork behavior (coefficient of determination [Rs2] = 0.267, P < 0.001). Conclusions: Among incoming internal medicine interns, teamwork training by expert demonstration resulted in similar teamwork behavior to participation in high-fidelity simulation and was more effective than traditional didactics. Clinical performance was largely independent of teamwork behavior and did not differ between training modalities. PMID:25730661

Fractional Brownian motion and long term clinical trial recruitment

PubMed Central

Zhang, Qiang; Lai, Dejian

2015-01-01

Prediction of recruitment in clinical trials has been a challenging task. Many methods have been studied, including models based on Poisson process and its large sample approximation by Brownian motion (BM), however, when the independent incremental structure is violated for BM model, we could use fractional Brownian motion to model and approximate the underlying Poisson processes with random rates. In this paper, fractional Brownian motion (FBM) is considered for such conditions and compared to BM model with illustrated examples from different trials and simulations. PMID:26347306

Fractional Brownian motion and long term clinical trial recruitment.

PubMed

Zhang, Qiang; Lai, Dejian

2011-05-01

Prediction of recruitment in clinical trials has been a challenging task. Many methods have been studied, including models based on Poisson process and its large sample approximation by Brownian motion (BM), however, when the independent incremental structure is violated for BM model, we could use fractional Brownian motion to model and approximate the underlying Poisson processes with random rates. In this paper, fractional Brownian motion (FBM) is considered for such conditions and compared to BM model with illustrated examples from different trials and simulations.

Combining macula clinical signs and patient characteristics for age-related macular degeneration diagnosis: a machine learning approach.

PubMed

Fraccaro, Paolo; Nicolo, Massimo; Bonetto, Monica; Giacomini, Mauro; Weller, Peter; Traverso, Carlo Enrico; Prosperi, Mattia; OSullivan, Dympna

2015-01-27

To investigate machine learning methods, ranging from simpler interpretable techniques to complex (non-linear) "black-box" approaches, for automated diagnosis of Age-related Macular Degeneration (AMD). Data from healthy subjects and patients diagnosed with AMD or other retinal diseases were collected during routine visits via an Electronic Health Record (EHR) system. Patients' attributes included demographics and, for each eye, presence/absence of major AMD-related clinical signs (soft drusen, retinal pigment epitelium, defects/pigment mottling, depigmentation area, subretinal haemorrhage, subretinal fluid, macula thickness, macular scar, subretinal fibrosis). Interpretable techniques known as white box methods including logistic regression and decision trees as well as less interpreitable techniques known as black box methods, such as support vector machines (SVM), random forests and AdaBoost, were used to develop models (trained and validated on unseen data) to diagnose AMD. The gold standard was confirmed diagnosis of AMD by physicians. Sensitivity, specificity and area under the receiver operating characteristic (AUC) were used to assess performance. Study population included 487 patients (912 eyes). In terms of AUC, random forests, logistic regression and adaboost showed a mean performance of (0.92), followed by SVM and decision trees (0.90). All machine learning models identified soft drusen and age as the most discriminating variables in clinicians' decision pathways to diagnose AMD. Both black-box and white box methods performed well in identifying diagnoses of AMD and their decision pathways. Machine learning models developed through the proposed approach, relying on clinical signs identified by retinal specialists, could be embedded into EHR to provide physicians with real time (interpretable) support.

Observational studies of patients in the emergency department: a comparison of 4 sampling methods.

PubMed

Valley, Morgan A; Heard, Kennon J; Ginde, Adit A; Lezotte, Dennis C; Lowenstein, Steven R

2012-08-01

We evaluate the ability of 4 sampling methods to generate representative samples of the emergency department (ED) population. We analyzed the electronic records of 21,662 consecutive patient visits at an urban, academic ED. From this population, we simulated different models of study recruitment in the ED by using 2 sample sizes (n=200 and n=400) and 4 sampling methods: true random, random 4-hour time blocks by exact sample size, random 4-hour time blocks by a predetermined number of blocks, and convenience or "business hours." For each method and sample size, we obtained 1,000 samples from the population. Using χ(2) tests, we measured the number of statistically significant differences between the sample and the population for 8 variables (age, sex, race/ethnicity, language, triage acuity, arrival mode, disposition, and payer source). Then, for each variable, method, and sample size, we compared the proportion of the 1,000 samples that differed from the overall ED population to the expected proportion (5%). Only the true random samples represented the population with respect to sex, race/ethnicity, triage acuity, mode of arrival, language, and payer source in at least 95% of the samples. Patient samples obtained using random 4-hour time blocks and business hours sampling systematically differed from the overall ED patient population for several important demographic and clinical variables. However, the magnitude of these differences was not large. Common sampling strategies selected for ED-based studies may affect parameter estimates for several representative population variables. However, the potential for bias for these variables appears small. Copyright © 2012. Published by Mosby, Inc.

Super-resolution structured illumination in optically thick specimens without fluorescent tagging

NASA Astrophysics Data System (ADS)

Hoffman, Zachary R.; DiMarzio, Charles A.

2017-11-01

This research extends the work of Hoffman et al. to provide both sectioning and super-resolution using random patterns within thick specimens. Two methods of processing structured illumination in reflectance have been developed without the need for a priori knowledge of either the optical system or the modulation patterns. We explore the use of two deconvolution algorithms that assume either Gaussian or sparse priors. This paper will show that while both methods accomplish their intended objective, the sparse priors method provides superior resolution and contrast against all tested targets, providing anywhere from ˜1.6× to ˜2× resolution enhancement. The methods developed here can reasonably be implemented to work without a priori knowledge about the patterns or point spread function. Further, all experiments are run using an incoherent light source, unknown random modulation patterns, and without the use of fluorescent tagging. These additional modifications are challenging, but the generalization of these methods makes them prime candidates for clinical application, providing super-resolved noninvasive sectioning in vivo.

Influence of Prior Heart Failure Hospitalization on Cardiovascular Events in Patients with Reduced and Preserved Ejection Fraction

PubMed Central

Bello, Natalie A.; Claggett, Brian; Desai, Akshay S.; McMurray, John J.V.; Granger, Christopher B.; Yusuf, Salim; Swedberg, Karl; Pfeffer, Marc A.; Solomon, Scott D.

2014-01-01

Background Hospitalization for acute heart failure (HF) is associated with high rates of subsequent mortality and readmission. We assessed the influence of the time interval between prior HF hospitalization and randomization in the CHARM trials on clinical outcomes in patients with both reduced and preserved ejection fraction. Methods and Results CHARM enrolled 7,599 patients with NYHA class II-IV heart failure, of whom 5,426 had a history of prior HF hospitalization. Cox proportional hazards regression models were utilized to assess the association between time from prior HF hospitalization and randomization and the primary outcome of cardiovascular death or unplanned admission to hospital for the management of worsening HF over a median of 36.6 months. For patients with HF and reduced (HFrEF) or preserved (HFpEF) ejection fraction, rates of CV mortality and HF hospitalization were higher among patients with prior HF hospitalization than those without. The risk for mortality and hospitalization varied inversely with the time interval between hospitalization and randomization. Rates were higher for HFrEF patients within each category. Event rates for those with HFpEF and a HF hospitalization in the 6 months prior to randomization were comparable to the rate in HFrEF patients with no prior HF hospitalization. Conclusions Rates of CV death or HF hospitalization are greatest in those who have been previously hospitalized for HF. Independent of EF, rates of death and readmission decline as time from HF hospitalization to trial enrollment increased. Recent HF hospitalization identifies a high risk population for future clinical trials in HFrEF and HFpEF. Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00634400. PMID:24874200

Design Features of the Diabetes and Periodontal Therapy Trial (DPTT): A Multicenter Randomized Single-Masked Clinical Trial Testing the Effect of Non-surgical Periodontal Therapy on Glycosylated Hemoglobin (HbA1c) Levels in Subjects with Type 2 Diabetes and Chronic Periodontitis

PubMed Central

2013-01-01

Background Evidence suggests that periodontitis is associated with prevalent and incident type 2 diabetes mellitus (T2DM), raising the question of whether periodontitis treatment may improve glycemic control in patients with T2DM. Meta-analyses of mostly small clinical trials suggest that periodontitis treatment results in a modest reduction in glycosylated hemoglobin (Hb) A1c. Purpose The purpose of the Diabetes and Periodontal Therapy Trial (DPTT) was to determine if periodontal treatment reduces HbA1c in patients with T2DM and periodontitis. Methods DPTT was a phase-III, single-masked, multi-center, randomized trial with a planned enrollment of 600 participants. Participants were randomly assigned to receive periodontal treatment immediately (Treatment Group) or after 6 months (Control Group). HbA1c values and clinical periodontal measures were determined at baseline and 3 and 6 months following randomization. Medication usage and dosing were assessed at each visit. Periodontal treatment consisted of scaling and root planing for a minimum of two 90-minute sessions, plus the use of an antibacterial mouth rinse for at least 32 days afterwards. The primary outcome was change in HbA1c from baseline to 6 months and the trial was powered to detect a between-group difference of 0.6%. Secondary outcomes included changes in periodontal clinical measures, fasting plasma glucose, the Homeostasis Model Assessment (HOMA2) and the need for rescue diabetes or periodontal therapy. Conclusion Dental and medical researchers collaborated to recruit, treat and monitor participants with two chronic diseases to determine if treatment of one condition affects the status of the other. PMID:24080100

Inpatient versus Outpatient Management of TIA or Minor Stroke: Clinical Outcome

PubMed Central

Majidi, Shahram; Leon Guerrero, Christopher R.; Burger, Kathleen M.; Rothrock, John F.

2017-01-01

Background The management of patients with acute transient ischemic attack (TIA) or minor stroke is highly variable. Whether hospitalization of such patients significantly improves short-term clinical outcome is unknown. We assessed the short-term clinical outcome associated with inpatient versus outpatient management of patients with TIA or minor stroke. Methods We evaluated a consecutive series of patients with acute TIA or minor ischemic stroke (NIH Stroke Scale score ≤ 3) presenting to a single emergency department (ED). We randomized patients to either hospital-based or outpatient-based management. All patients underwent interview and examination 7–10 days following the index event. Results This study included 100 patients, 41 with TIA and 59 with minor stroke. Nineteen (46%) of the TIA patients and 29 (49%) of the minor stroke patients randomized to hospital management, and the remaining 22 TIA patients and 30 minor stroke patients randomized to outpatient-based management. In the patients with a minor stroke, neurologic worsening occurred in 6 out of 29 (21%) in the inpatient arm compared with 3 out of 30 (10%) in the outpatient arm (p = 0.3). In none of these cases was acute interventional therapy or need for urgent admission considered medically appropriate. In the patients with a TIA, recurrence of a TIA occurred in 2 out of 19 (11%) in the inpatient arm compared with 2 out of 22 (9%) in the outpatient arm (p = 1). None of the patients with a TIA randomized to the inpatient arm experienced a stroke compared with 1 out of 22 in the outpatient arm (p = 1). There were no deaths in either group. Conclusion Routine hospitalization of all patients with TIA or minor ischemic stroke may not positively affect short-term clinical outcome. PMID:28702120

Enhancing Cardiac Rehabilitation With Stress Management Training: A Randomized Clinical Efficacy Trial

PubMed Central

Blumenthal, James A.; Sherwood, Andrew; Smith, Patrick J.; Watkins, Lana; Mabe, Stephanie; Kraus, William E.; Ingle, Krista; Miller, Paula; Hinderliter, Alan

2016-01-01

Background Cardiac rehabilitation (CR) is the standard of care for patients with coronary heart disease (CHD). Despite considerable epidemiologic evidence that high stress is associated with worse health outcomes, stress management training (SMT) is not included routinely as a component of CR. Methods and Results 151 outpatients with CHD aged 36 to 84 years were randomized to 12-weeks of comprehensive CR or comprehensive CR combined with SMT (CR+SMT), with assessments of stress and CHD biomarkers obtained before and after treatment. A matched sample of CR-eligible patients who did not receive CR comprised a No-CR comparison group. All participants were followed for up to 5.3 years (median = 3.2 years) for clinical events. Patients randomized to CR+SMT exhibited greater reductions in composite stress levels compared with those randomized to CR alone (P = 0.022), an effect that was driven primarily by improvements in anxiety, distress, and perceived stress. Both CR groups achieved significant, and comparable, improvements in CHD biomarkers. Participants in the CR+SMT group exhibited lower rates of clinical events compared with CR alone (18% vs. 33%, HR = 0.49 [0.25, 0.95], P = 0.035) and both CR groups had lower event rates compared to the No-CR group (47%, HR = 0.44 [0.27, 0.71], P < .001). Conclusions CR enhanced by SMT produced significant reductions in stress and greater improvements in medical outcomes compared with standard CR. Our findings indicate that SMT may provide incremental benefit when combined with comprehensive CR and suggest that SMT should be incorporated routinely into CR. Clinical Trial Registration Information www.Clinicaltrials.gov. Identifier: NCT00981253. PMID:27045127

The Effect of Adjuvant Zinc Therapy on Recovery from Pneumonia in Hospitalized Children: A Double-Blind Randomized Controlled Trial

PubMed Central

Qasemzadeh, Mohammad Javad; Fathi, Mahdi; Tashvighi, Maryam; Gharehbeglou, Mohammad; Yadollah-Damavandi, Soheila; Parsa, Yekta; Rahimi, Ebrahim

2014-01-01

Objectives. Pneumonia is one of the common mortality causes in young children. Some studies have shown beneficial effect of zinc supplements on treatment of pneumonia. The present study aimed to investigate the effects of short courses of zinc administration on recovery from this disease in hospitalized children. Methods. In a parallel Double-Blind Randomized Controlled Trial at Ayatollah Golpaygani Hospital in Qom, 120 children aged 3–60 months with pneumonia were randomly assigned 1 : 1 to receive zinc or placebo (5 mL every 12 hours) along with the common antibiotic treatments until discharge. Primary outcome was recovery from pneumonia which included the incidence and resolving clinical symptoms and duration of hospitalization. Results. The difference between two groups in all clinical symptoms at admittance and the variables affecting the disease such as age and sex were not statistically significant (P < 0.05) at baseline. Compared to the placebo group, the treatment group showed a statistically significant decrease in duration of clinical symptoms (P = 0.044) and hospitalization (P = 0.004). Conclusions. Supplemental administration of zinc can expedite the healing process and results in faster resolution of clinical symptoms in children with pneumonia. In general, zinc administration, along with common antibiotic treatments, is recommended in this group of children. It can also reduce the drug resistance caused by multiple antibiotic therapies. This trial is approved by Medical Ethic Committee of Islamic Azad University in Iran (ID Number: 8579622-Q). This study is also registered in AEARCTR (The American Economic Association's Registry for Randomized Controlled Trials). This trial is registered with RCT ID: AEARCTR-0000187. PMID:24955282

Feasibility of a clinical trial of vision therapy for treatment of amblyopia.

PubMed

Lyon, Don W; Hopkins, Kristine; Chu, Raymond H; Tamkins, Susanna M; Cotter, Susan A; Melia, B Michele; Holmes, Jonathan M; Repka, Michael X; Wheeler, David T; Sala, Nicholas A; Dumas, Janette; Silbert, David I

2013-05-01

We conducted a pilot randomized clinical trial of office-based active vision therapy for the treatment of childhood amblyopia to determine the feasibility of conducting a full-scale randomized clinical trial. A training and certification program and manual of procedures were developed to certify therapists to administer a standardized vision therapy program in ophthalmology and optometry offices consisting of weekly visits for 16 weeks. Nineteen children, aged 7 to less than 13 years, with amblyopia (20/40-20/100) were randomly assigned to receive either 2 hours of daily patching with active vision therapy or 2 hours of daily patching with placebo vision therapy. Therapists in diverse practice settings were successfully trained and certified to perform standardized vision therapy in strict adherence with protocol. Subjects completed 85% of required weekly in-office vision therapy visits. Eligibility criteria based on age, visual acuity, and stereoacuity, designed to identify children able to complete a standardized vision therapy program and judged likely to benefit from this treatment, led to a high proportion of screened subjects being judged ineligible, resulting in insufficient recruitment. There were difficulties in retrieving adherence data for the computerized home therapy procedures. This study demonstrated that a 16-week treatment trial of vision therapy was feasible with respect to maintaining protocol adherence; however, recruitment under the proposed eligibility criteria, necessitated by the standardized approach to vision therapy, was not successful. A randomized clinical trial of in-office vision therapy for the treatment of amblyopia would require broadening of the eligibility criteria and improved methods to gather objective data regarding the home therapy. A more flexible approach that customizes vision therapy based on subject age, visual acuity, and stereopsis might be required to allow enrollment of a broader group of subjects.

Clarithromycin vs. Gemifloxacin in Quadruple Therapy Regimens for Empiric Primary Treatment of Helicobacter pylori Infection: A Randomized Clinical Trial

PubMed Central

Masoodi, Mohsen; Talebi-Taher, Mahshid; Tabatabaie, Khadijeh; Khaleghi, Siamak; Faghihi, Amir-Hossein; Agah, Shahram; Asadi, Reyhaneh

2015-01-01

BACKGROUND Eradication of Helicobacter pylori infection plays a crucial role in the treatment of peptic ulcer. Clarithromycin resistance is a major cause of treatment failure. This randomized clinical trial aimed at evaluating the efficacy of a clarithromycin versus gemifloxacin containing quadruple therapy regimen in eradication of H.pylori infection. METHODS In this randomized double blind clinical trial (RCT 2012102011054N2), a total of 120 patients were randomized to two groups of 60 patients each. Patients with proven H.pylori infection were consecutively assigned into two groups to receive OBAG or OBAC in gastroenterology clinic in Rasoul-e- Akram General Hospital in Tehran, Iran. The patients in the OBAG group received omeprazole (20 mg) twice daily, bismuth subcitrate (240 mg) twice daily, amoxicillin (1 gr) twice daily, and gemifloxacin (320 mg) once daily, and those in the OBAC group received omeprazole (20 mg) twice daily, 240 mg of bismuth subcitrate twice daily, amoxicillin (1 gr) twice daily, and clarithromycin (500 mg) twice daily for 10 days. RESULTS Five patients from each group were excluded from the study because of poor compliance, so 110 patients completed the study. The intention-to-treat eradication rate was 61.6% and 66.6% for the OBAC and OBAG groups, respectively. According to the per protocol analysis, the success rates of eradication of H.pylori infection were 67.2% and 72.7% for OBAC and OBAG groups, respectively (p=0.568). CONCLUSION The results of this study suggest that gemifloxacin containing regimen is at least as effective as clarithromycin regimen; hence, this new treatment could be considered as an alternative for the patients who cannot tolerate clarithromycin. PMID:26106468

A Randomized Trial Testing the Impact of Narrative Vignettes vs. Guideline Summaries on Provider Response to a Professional Organization Clinical Policy for Safe Opioid Prescribing

PubMed Central

Meisel, Zachary F.; Metlay, Joshua P.; Sinnenberg, Lauren; Kilaru, Austin S.; Grossestreuer, Anne; Barg, Frances K.; Shofer, Frances S.; Rhodes, Karin V.; Perrone, Jeanmarie

2016-01-01

Background Clinical guidelines are known to be underused by practitioners. In response to the challenges of treating pain amidst a prescription opioid epidemic, the American College of Emergency Physicians published an evidence-based clinical policy for opioid prescribing in 2012. Evidence-based narratives, an effective method of communicating health information in a variety of settings, offer a novel strategy for disseminating guidelines to physicians and engaging providers with clinical evidence. Objectives To compare whether narrative vignettes embedded in the American College of Emergency Physician (ACEP) daily e-newsletter improved dissemination of the clinical policy to ACEP members, and engagement of members with the clinical policy, compared to traditional summary text. Methods A prospective randomized controlled study, entitled Stories to Promote Information using Narrative (SPIN) trial, was performed. Derived from qualitative interviews with 61 ACEP physicians, 4 narrative vignettes were selected and refined, using a consensus panel of clinical and implementation experts. All ACEP members were then block randomized by state of residence to receive alternative versions of a daily emailed newsletter for a total of 24 days during a 9 week period. Narrative newsletters contained a selection of vignettes that referenced opioid prescription dilemmas. Control newsletters contained a selection of descriptive text about the clinical policy using similar length and appearance to the narrative vignettes. Embedded in the newsletters were web links to the complete vignette or traditional summary text, as well as additional links to the full ACEP clinical policy and a website providing assistance with prescription drug monitoring program enrollment. The newsletters were otherwise identical. Outcomes measured were the percentage of subjects who visited any of the web pages that contained additional guideline related information and the odds of any unique physician visiting these web pages during the study. Results 27,592 physicians were randomized and 21,226 received the newsletter during the study period. When counting each physician once over the study period, there were 509 unique visitors in the narrative group and 173 unique visitors in the control group (4.8% vs. 1.6%, difference 3.2% 95%CI 2.7%-3.7%). There were 744 gross visits from the e-newsletter to any of the three web pages in the narrative group compared to 248 in the control group (7.0% vs. 2.3%, OR 3.2 (95% CI 2.7-3.6). Over the course of the study, the odds ratio of any physician in the narrative group visiting one of the three informational web sites compared to the control group was 3.1 (95% CI 2.6-3.6). Conclusion Among a national sample of emergency physicians, narrative vignettes outperformed traditional guideline text in promoting engagement with an evidence-based clinical guideline related to opioid prescriptions. PMID:27133392

Patellar denervation with electrocautery in total knee arthroplasty without patellar resurfacing: a meta-analysis.

PubMed

Cheng, Tao; Zhu, Chen; Guo, Yongyuan; Shi, Sifeng; Chen, Desheng; Zhang, Xianlong

2014-11-01

The impact of patellar denervation with electrocautery in total knee arthroplasty (TKA) on post-operative outcomes has been under debate. This study aims to conduct a meta-analysis and systematic review to compare the benefits and risks of circumpatellar electrocautery with those of non-electrocautery in primary TKAs. Comparative and randomized clinical studies were identified by conducting an electronic search of articles dated up to September 2012 in PubMed, EMBASE, Scopus, and the Cochrane databases. Six studies that focus on a total of 849 knees were analysed. A random-effects model was conducted using the inverse-variance method for continuous variables and the Mantel-Haenszel method for dichotomous variables. There was no significant difference in the incidence of anterior knee pain between the electrocautery and non-electrocautery groups. In term of patellar score and Knee Society Score, circumpatellar electrocautery improved clinical outcomes compared with non-electrocautery in TKAs. The statistical differences were in favour of the electrocautery group but have minimal clinical significance. In addition, the overall complications indicate no statistical significance between the two groups. This study shows no strong evidence either for or against electrocautery compared with non-electrocautery in TKAs. Therapeutic study (systematic review and meta-analysis), Level III.

A varying-coefficient method for analyzing longitudinal clinical trials data with nonignorable dropout

PubMed Central

Forster, Jeri E.; MaWhinney, Samantha; Ball, Erika L.; Fairclough, Diane

2011-01-01

Dropout is common in longitudinal clinical trials and when the probability of dropout depends on unobserved outcomes even after conditioning on available data, it is considered missing not at random and therefore nonignorable. To address this problem, mixture models can be used to account for the relationship between a longitudinal outcome and dropout. We propose a Natural Spline Varying-coefficient mixture model (NSV), which is a straightforward extension of the parametric Conditional Linear Model (CLM). We assume that the outcome follows a varying-coefficient model conditional on a continuous dropout distribution. Natural cubic B-splines are used to allow the regression coefficients to semiparametrically depend on dropout and inference is therefore more robust. Additionally, this method is computationally stable and relatively simple to implement. We conduct simulation studies to evaluate performance and compare methodologies in settings where the longitudinal trajectories are linear and dropout time is observed for all individuals. Performance is assessed under conditions where model assumptions are both met and violated. In addition, we compare the NSV to the CLM and a standard random-effects model using an HIV/AIDS clinical trial with probable nonignorable dropout. The simulation studies suggest that the NSV is an improvement over the CLM when dropout has a nonlinear dependence on the outcome. PMID:22101223

Dental Students’ Preference with Regard to Tactile or Visual Determination of Injection Site for an Inferior Alveolar Nerve Block in Children: A Crossover Randomized Clinical Trial

PubMed Central

Iranmanesh, Seyed Masoud

2016-01-01

Objectives: Instruction of local anesthesia injection in an important part of dental education curricula. This study was performed to compare dental students’ preference with regard to tactile or visual determination of injection site for an inferior alveolar nerve block (IANB) in children. Materials and Methods: This crossover randomized clinical trial was conducted on dental students of Zahedan Dental School who took the first practical course of pediatric dentistry in the first academic semester of 2013–14 (n=42). They were randomly divided into two groups. During the first phase, group I was instructed to find the needle insertion point for an IANB via tactile method and group II was instructed to do it visually. In the second phase, the groups received instructions for the alternate technique. Both instructions were done using live demonstrations by the same instructor and immediately after instruction the learners practiced an IANB using the taught method. A five-point Likert scale questionnaire was then filled out by the students. The preference score was determined by calculating the mean of item scores. Data were analyzed using Mann-Whitney U and Wilcoxon Singed Rank tests in SPSS 19 at P=0.05 level of significance. Results: Thirty-eight students completed the study. By using the visual method to perform an IANB, students gained a significantly higher mean preference score (P=0.020). There was a significant difference in the preference of male students (P=0.008). Conclusions: Instruction of IANB by visual identification of needle insertion point is more desirable by students. PMID:27536327

Translating Basic Behavioral and Social Science Research to Clinical Application: The EVOLVE Mixed Methods Approach

PubMed Central

Peterson, Janey C.; Czajkowski, Susan; Charlson, Mary E.; Link, Alissa R.; Wells, Martin T.; Isen, Alice M.; Mancuso, Carol A.; Allegrante, John P.; Boutin-Foster, Carla; Ogedegbe, Gbenga; Jobe, Jared B.

2012-01-01

Objective To describe a mixed-methods approach to develop and test a basic behavioral science-informed intervention to motivate behavior change in three high-risk clinical populations. Our theoretically-derived intervention comprised a combination of positive affect and self-affirmation (PA/SA) which we applied to three clinical chronic disease populations. Methods We employed a sequential mixed methods model (EVOLVE) to design and test the PA/SA intervention in order to increase physical activity in people with coronary artery disease (post-percutaneous coronary intervention [PCI]) or asthma (ASM), and to improve medication adherence in African Americans with hypertension (HTN). In an initial qualitative phase, we explored participant values and beliefs. We next pilot tested and refined the intervention, and then conducted three randomized controlled trials (RCTs) with parallel study design. Participants were randomized to combined PA/SA vs. an informational control (IC) and followed bimonthly for 12 months, assessing for health behaviors and interval medical events. Results Over 4.5 years, we enrolled 1,056 participants. Changes were sequentially made to the intervention during the qualitative and pilot phases. The three RCTs enrolled 242 PCI, 258 ASM and 256 HTN participants (n=756). Overall, 45.1% of PA/SA participants versus 33.6% of IC participants achieved successful behavior change (p=0.001). In multivariate analysis PA/SA intervention remained a significant predictor of achieving behavior change (p<0.002, OR=1.66, 95% CI 1.22–2.27), controlling for baseline negative affect, comorbidity, gender, race/ethnicity, medical events, smoking and age. Conclusions The EVOLVE method is a means by which basic behavioral science research can be translated into efficacious interventions for chronic disease populations. PMID:22963594

Multicenter Randomized Trial of Robot-Assisted Rehabilitation for Chronic Stroke: Methods and Entry Characteristics for VA ROBOTICS

PubMed Central

Lo, Albert C.; Guarino, Peter; Krebs, Hermano I.; Volpe, Bruce T.; Bever, Christopher T.; Duncan, Pamela W.; Ringer, Robert J.; Wagner, Todd H.; Richards, Lorie G.; Bravata, Dawn M.; Haselkorn, Jodie K.; Wittenberg, George F.; Federman, Daniel G.; Corn, Barbara H.; Maffucci, Alysia D.; Peduzzi, Peter

2017-01-01

Background Chronic upper extremity impairment due to stroke has significant medical, psychosocial, and financial consequences, but few studies have examined the effectiveness of rehabilitation therapy during the chronic stroke period. Objective To test the safety and efficacy of the MIT-Manus robotic device for chronic upper extremity impairment following stroke. Methods The VA Cooperative Studies Program initiated a multicenter, randomized, controlled trial in November 2006 (VA ROBOTICS). Participants with upper extremity impairment ≥6 months poststroke were randomized to robot-assisted therapy (RT), intensive comparison therapy (ICT), or usual care (UC). RT and ICT consisted of three 1-hour treatment sessions per week for 12 weeks. The primary outcome was change in the Fugl-Meyer Assessment upper extremity motor function score at 12 weeks relative to baseline. Secondary outcomes included the Wolf Motor Function Test and the Stroke Impact Scale. Results A total of 127 participants were randomized: 49 to RT, 50 to ICT, and 28 to UC. The majority of participants were male (96%), with a mean age of 65 years. The primary stroke type was ischemic (85%), and 58% of strokes occurred in the anterior circulation. Twenty percent of the participants reported a stroke in addition to their index stroke. The average time from the index stroke to enrollment was 56 months (range, 6 months to 24 years). The mean Fugl-Meyer score at entry was 18.9. Conclusions VA ROBOTICS demonstrates the feasibility of conducting multicenter clinical trials to rigorously test new rehabilitative devices before their introduction to clinical practice. The results are expected in early 2010. PMID:19541917

Randomization to Standard and Concise Informed Consent Forms: Development of Evidence-Based Consent Practices

PubMed Central

Enama, Mary E.; Hu, Zonghui; Gordon, Ingelise; Costner, Pamela; Ledgerwood, Julie E.; Grady, Christine

2012-01-01

Background Consent to participate in research is an important component of the conduct of ethical clinical trials. Current consent practices are largely policy-driven. This study was conducted to assess comprehension of study information and satisfaction with the consent form between subjects randomized to concise or to standard informed consent forms as one approach to developing evidence-based consent practices. Methods Participants (N=111) who enrolled into two Phase I investigational influenza vaccine protocols (VRC 306 and VRC 307) at the NIH Clinical Center were randomized to one of two IRB-approved consents; either a standard or concise form. Concise consents had an average of 63% fewer words. All other aspects of the consent process were the same. Questionnaires about the study and the consent process were completed at enrollment and at the last visit in both studies. Results Subjects using concise consent forms scored as well as those using standard length consents in measures of comprehension (7 versus 7, p=0.79 and 20 versus 21, p=0.13), however, the trend was for the concise consent group to report feeling better informed. Both groups thought the length and detail of the consent form was appropriate. Conclusions Randomization of study subjects to different length IRB-approved consents forms as one method for developing evidence-based consent practices, resulted in no differences in study comprehension or satisfaction with the consent form. A concise consent form may be used ethically in the context of a consent process conducted by well-trained staff with opportunities for discussion and education throughout the study. PMID:22542645

Adaptive Localization of Focus Point Regions via Random Patch Probabilistic Density from Whole-Slide, Ki-67-Stained Brain Tumor Tissue

PubMed Central

Alomari, Yazan M.; MdZin, Reena Rahayu

2015-01-01

Analysis of whole-slide tissue for digital pathology images has been clinically approved to provide a second opinion to pathologists. Localization of focus points from Ki-67-stained histopathology whole-slide tissue microscopic images is considered the first step in the process of proliferation rate estimation. Pathologists use eye pooling or eagle-view techniques to localize the highly stained cell-concentrated regions from the whole slide under microscope, which is called focus-point regions. This procedure leads to a high variety of interpersonal observations and time consuming, tedious work and causes inaccurate findings. The localization of focus-point regions can be addressed as a clustering problem. This paper aims to automate the localization of focus-point regions from whole-slide images using the random patch probabilistic density method. Unlike other clustering methods, random patch probabilistic density method can adaptively localize focus-point regions without predetermining the number of clusters. The proposed method was compared with the k-means and fuzzy c-means clustering methods. Our proposed method achieves a good performance, when the results were evaluated by three expert pathologists. The proposed method achieves an average false-positive rate of 0.84% for the focus-point region localization error. Moreover, regarding RPPD used to localize tissue from whole-slide images, 228 whole-slide images have been tested; 97.3% localization accuracy was achieved. PMID:25793010

Zhen Gan Xi Feng Decoction, a Traditional Chinese Herbal Formula, for the Treatment of Essential Hypertension: A Systematic Review of Randomized Controlled Trials

PubMed Central

Xiong, Xingjiang; Yang, Xiaochen; Feng, Bo; Liu, Wei; Duan, Lian; Gao, Ao; Li, Haixia; Ma, Jizheng; Du, Xinliang; Li, Nan; Wang, Pengqian; Su, Kelei; Chu, Fuyong; Zhang, Guohao; Li, Xiaoke; Wang, Jie

2013-01-01

Objectives. To assess the clinical effectiveness and adverse effects of Zhen Gan Xi Feng Decoction (ZGXFD) for essential hypertension (EH). Methods. Five major electronic databases were searched up to August 2012 to retrieve any potential randomized controlled trials designed to evaluate the clinical effectiveness of ZGXFD for EH reported in any language, with main outcome measure as blood pressure (BP). Results. Six randomized trials were included. Methodological quality of the trials was evaluated as generally low. Four trials compared prescriptions based on ZGXFD with antihypertensive drugs. Meta-analysis showed that ZGXFD was more effective in BP control and TCM syndrome and symptom differentiation (TCM-SSD) scores than antihypertensive drugs. Two trials compared the combination of modified ZGXFD plus antihypertensive drugs with antihypertensive drugs. Meta-analysis showed that there is significant beneficial effect on TCM-SSD scores. However, no significant effect on BP was found. The safety of ZGXFD is still uncertain. Conclusions. ZGXFD appears to be effective in improving blood pressure and hypertension-related symptoms for EH. However, the evidence remains weak due to poor methodological quality of the included studies. More rigorous trials are warranted to support their clinical use. PMID:23573163

Chronic obstructive pulmonary disease self-management activation research trial (COPD-SMART): results of recruitment and baseline patient characteristics.

PubMed

Russo, Rennie; Coultas, David; Ashmore, Jamile; Peoples, Jennifer; Sloan, John; Jackson, Bradford E; Uhm, Minyong; Singh, Karan P; Blair, Steven N; Bae, Sejong

2015-03-01

To describe the recruitment methods, study participation rate, and baseline characteristics of a representative sample of outpatients with COPD eligible for pulmonary rehabilitation participating in a trial of a lifestyle behavioral intervention to increase physical activity. A patient registry was developed for recruitment using an administrative database from primary care and specialty clinics of an academic medical center in northeast Texas for a parallel group randomized trial. The registry was comprised of 5582 patients and over the course of the 30 month recruitment period 325 patients were enrolled for an overall study participation rate of 35.1%. After a 6-week COPD self-management education period provided to all enrolled patients, 305 patients were randomized into either usual care (UC; n=156) or the physical activity self-management intervention (PASM; n=149). There were no clinically significant differences in demographics, clinical characteristics, or health status indicators between the randomized groups. The results of this recruitment process demonstrate the successful use of a patient registry for enrolling a representative sample of outpatients eligible for pulmonary rehabilitation with COPD from primary and specialty care. Moreover, this approach to patient recruitment provides a model for future studies utilizing administrative databases and electronic health records. Published by Elsevier Inc.

Effect of Kangfuxin Solution on Chemo/Radiotherapy-Induced Mucositis in Nasopharyngeal Carcinoma Patients: A Multicenter, Prospective Randomized Phase III Clinical Study

PubMed Central

Luo, Yangkun; Feng, Mei; Fan, Zixuan; Zhu, Xiaodong; Jin, Feng; Li, Rongqing; Wu, Jingbo; Yang, Xia; Jiang, Qinghua; Bai, Hongfang; Huang, Yecai; Lang, Jinyi

2016-01-01

Objective. To evaluate the efficacy and safety of Kangfuxin Solution, a pure Chinese herbal medicine, on mucositis induced by chemoradiotherapy in nasopharyngeal carcinoma patients. Methods. A randomized, parallel-group, multicenter clinical study was performed. A total of 240 patients were randomized to receive either Kangfuxin Solution (test group) or compound borax gargle (control group) during chemoradiotherapy. Oral mucositis, upper gastrointestinal mucositis, and oral pain were evaluated by Common Terminology Criteria for Adverse Events (CTCAE) v3.0 and the Verbal Rating Scale (VRS). Results. Of 240 patients enrolled, 215 were eligible for efficacy analysis. Compared with the control group, the incidence and severity of oral mucositis in the test group were significantly reduced (P = 0.01). The time to different grade of oral mucositis occurrence (grade 1, 2, or 3) was longer in test group (P < 0.01), and the accumulated radiation dose was also higher in test group comparing to the control group (P < 0.05). The test group showed lower incidence of oral pain and gastrointestinal mucositis than the control group (P < 0.01). No significant adverse events were observed. Conclusion. Kangfuxin Solution demonstrated its superiority to compound borax gargle on mucositis induced by chemoradiotherapy. Its safety is acceptable for clinical application. PMID:27375766

Do Implant Overdentures Improve Dietary Intake? A Randomized Clinical Trial

PubMed Central

Hamdan, N.M.; Gray-Donald, K.; Awad, M.A.; Johnson-Down, L.; Wollin, S.; Feine, J.S.

2013-01-01

People wearing mandibular two-implant overdentures (IOD) chew food with less difficulty than those wearing conventional complete dentures (CD). However, there is still controversy over whether or not this results in better dietary intake. In this randomized clinical trials (RCT), the amounts of total dietary fiber (TDF), macronutrients, 9 micronutrients, and energy in diets consumed by persons with IOD and CD were compared. Male and female edentate patients ≥ 65 yrs (n = 255) were randomly divided into 2 groups and assigned to receive a maxillary CD and either a mandibular IOD or a CD. One year following prosthesis delivery, 217 participants (CD = 114, IOD = 103) reported the food and quantities they consumed to a registered dietician through a standard 24-hour dietary recall method. The mean and median values of TDF, macro- and micronutrients, and energy consumed by both groups were calculated and compared analytically. No significant between-group differences were found (ps > .05). Despite quality-of-life benefits from IODs, this adequately powered study reveals no evidence of nutritional advantages for independently living medically healthy edentate elders wearing two-implant mandibular overdentures over those wearing conventional complete dentures in their dietary intake at one year following prosthesis delivery (International Clinical Trials ISRCTN24273915). PMID:24158335

3D exemplar-based random walks for tooth segmentation from cone-beam computed tomography images

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

Pei, Yuru, E-mail: peiyuru@cis.pku.edu.cn; Ai, Xin

Purpose: Tooth segmentation is an essential step in acquiring patient-specific dental geometries from cone-beam computed tomography (CBCT) images. Tooth segmentation from CBCT images is still a challenging task considering the comparatively low image quality caused by the limited radiation dose, as well as structural ambiguities from intercuspation and nearby alveolar bones. The goal of this paper is to present and discuss the latest accomplishments in semisupervised tooth segmentation with adaptive 3D shape constraints. Methods: The authors propose a 3D exemplar-based random walk method of tooth segmentation from CBCT images. The proposed method integrates semisupervised label propagation and regularization by 3Dmore » exemplar registration. To begin with, the pure random walk method is to get an initial segmentation of the teeth, which tends to be erroneous because of the structural ambiguity of CBCT images. And then, as an iterative refinement, the authors conduct a regularization by using 3D exemplar registration, as well as label propagation by random walks with soft constraints, to improve the tooth segmentation. In the first stage of the iteration, 3D exemplars with well-defined topologies are adapted to fit the tooth contours, which are obtained from the random walks based segmentation. The soft constraints on voxel labeling are defined by shape-based foreground dentine probability acquired by the exemplar registration, as well as the appearance-based probability from a support vector machine (SVM) classifier. In the second stage, the labels of the volume-of-interest (VOI) are updated by the random walks with soft constraints. The two stages are optimized iteratively. Instead of the one-shot label propagation in the VOI, an iterative refinement process can achieve a reliable tooth segmentation by virtue of exemplar-based random walks with adaptive soft constraints. Results: The proposed method was applied for tooth segmentation of twenty clinically captured CBCT images. Three metrics, including the Dice similarity coefficient (DSC), the Jaccard similarity coefficient (JSC), and the mean surface deviation (MSD), were used to quantitatively analyze the segmentation of anterior teeth including incisors and canines, premolars, and molars. The segmentation of the anterior teeth achieved a DSC up to 98%, a JSC of 97%, and an MSD of 0.11 mm compared with manual segmentation. For the premolars, the average values of DSC, JSC, and MSD were 98%, 96%, and 0.12 mm, respectively. The proposed method yielded a DSC of 95%, a JSC of 89%, and an MSD of 0.26 mm for molars. Aside from the interactive definition of label priors by the user, automatic tooth segmentation can be achieved in an average of 1.18 min. Conclusions: The proposed technique enables an efficient and reliable tooth segmentation from CBCT images. This study makes it clinically practical to segment teeth from CBCT images, thus facilitating pre- and interoperative uses of dental morphologies in maxillofacial and orthodontic treatments.« less

Quantitative comparison of randomization designs in sequential clinical trials based on treatment balance and allocation randomness.

PubMed

Zhao, Wenle; Weng, Yanqiu; Wu, Qi; Palesch, Yuko

2012-01-01

To evaluate the performance of randomization designs under various parameter settings and trial sample sizes, and identify optimal designs with respect to both treatment imbalance and allocation randomness, we evaluate 260 design scenarios from 14 randomization designs under 15 sample sizes range from 10 to 300, using three measures for imbalance and three measures for randomness. The maximum absolute imbalance and the correct guess (CG) probability are selected to assess the trade-off performance of each randomization design. As measured by the maximum absolute imbalance and the CG probability, we found that performances of the 14 randomization designs are located in a closed region with the upper boundary (worst case) given by Efron's biased coin design (BCD) and the lower boundary (best case) from the Soares and Wu's big stick design (BSD). Designs close to the lower boundary provide a smaller imbalance and a higher randomness than designs close to the upper boundary. Our research suggested that optimization of randomization design is possible based on quantified evaluation of imbalance and randomness. Based on the maximum imbalance and CG probability, the BSD, Chen's biased coin design with imbalance tolerance method, and Chen's Ehrenfest urn design perform better than popularly used permuted block design, EBCD, and Wei's urn design. Copyright © 2011 John Wiley & Sons, Ltd.

Cost-effectiveness of Recruitment Methods in an Obesity Prevention Trial for Young Children

PubMed Central

Robinson, Jodie L.; Fuerch, Janene H.; Winiewicz, Dana D.; Salvy, Sarah J.; Roemmich, James N.; Epstein, Leonard H.

2007-01-01

Background Recruitment of participants for clinical trials requires considerable effort and cost. There is no research on the cost-effectiveness of recruitment methods for an obesity prevention trial of young children. Methods This study determined the cost-effectiveness of recruiting 70 families with a child aged 4 to 7 (5.9 ± 1.3) years in Western New York from February, 2003 to November, 2004, for a two year randomized obesity prevention trial to reduce television watching in the home. Results Of the 70 randomized families, 65.7% (n = 46) were obtained through direct mailings, 24.3% (n = 17) were acquired through newspaper advertisements, 7.1 % (n = 5) from other sources (e.g. word of mouth), and 2.9% (n = 2) through posters and brochures. Costs of each recruitment method were computed by adding the cost of materials, staff time, and media expenses. Cost-effectiveness (money spent per randomized participant) was US $0 for other sources, US $227.76 for direct mailing, US $546.95 for newspaper ads, and US $3,020.84 for posters and brochures. Conclusion Of the methods with associated costs, direct mailing was the most cost effective in recruiting families with young children, which supports the growing literature of the effectiveness of direct mailing. PMID:17475318

Estimation of retinal vessel caliber using model fitting and random forests

NASA Astrophysics Data System (ADS)

Araújo, Teresa; Mendonça, Ana Maria; Campilho, Aurélio

2017-03-01

Retinal vessel caliber changes are associated with several major diseases, such as diabetes and hypertension. These caliber changes can be evaluated using eye fundus images. However, the clinical assessment is tiresome and prone to errors, motivating the development of automatic methods. An automatic method based on vessel crosssection intensity profile model fitting for the estimation of vessel caliber in retinal images is herein proposed. First, vessels are segmented from the image, vessel centerlines are detected and individual segments are extracted and smoothed. Intensity profiles are extracted perpendicularly to the vessel, and the profile lengths are determined. Then, model fitting is applied to the smoothed profiles. A novel parametric model (DoG-L7) is used, consisting on a Difference-of-Gaussians multiplied by a line which is able to describe profile asymmetry. Finally, the parameters of the best-fit model are used for determining the vessel width through regression using ensembles of bagged regression trees with random sampling of the predictors (random forests). The method is evaluated on the REVIEW public dataset. A precision close to the observers is achieved, outperforming other state-of-the-art methods. The method is robust and reliable for width estimation in images with pathologies and artifacts, with performance independent of the range of diameters.

Safety, Tolerability, and Immunogenicity of the Novel Antituberculous Vaccine RUTI: Randomized, Placebo-Controlled Phase II Clinical Trial in Patients with Latent Tuberculosis Infection

PubMed Central

Nell, Andre S.; D’lom, Eva; Bouic, Patrick; Sabaté, Montserrat; Bosser, Ramon; Picas, Jordi; Amat, Mercè; Churchyard, Gavin; Cardona, Pere-Joan

2014-01-01

Objectives To evaluate the safety, tolerability and immunogenicity of three different doses (5, 25 and 50 µg) of the novel antituberculous vaccine RUTI compared to placebo in subjects with latent tuberculosis infection. Methods and Findings Double-blind, randomized, placebo-controlled Phase II Clinical Trial (95 patients randomized). Three different RUTI doses and placebo were tested, randomized both in HIV-positive (n = 47) and HIV-negative subjects (n = 48), after completion of one month isoniazid (INH) pre-vaccination. Each subject received two vaccine administrations, 28 Days apart. Five patients withdrew and 90 patients completed the study. Assessment of safety showed no deaths during study. Two subjects had serious adverse events one had a retinal detachment while taking INH and was not randomized and the other had a severe local injection site abscess on each arm and was hospitalized; causality was assessed as very likely and by the end of the study the outcome had resolved. All the patients except 5 (21%) patients of the placebo group (3 HIV+ and 2 HIV−) reported at least one adverse event (AE) during the study. The most frequently occurring AEs among RUTI recipients were (% in HIV+/−): injection site reactions [erythema (91/92), induration (94/92), local nodules (46/25), local pain (66/75), sterile abscess (6/6), swelling (74/83), ulcer (20/11), headache (17/22) and nasopharyngitis (20/5)]. These events were mostly mild and well tolerated. Overall, a polyantigenic response was observed, which differed by HIV− status. The best polyantigenic response was obtained when administrating 25 µg RUTI, especially in HIV-positive subjects which was not increased after the second inoculation. Conclusion This Phase II clinical trial demonstrates reasonable tolerability of RUTI. The immunogenicity profile of RUTI vaccine in LTBI subjects, even being variable among groups, allows us considering one single injection of one of the highest doses in future trials, preceded by an extended safety clinical phase. Trial Registration ClinicalTrials.gov NCT01136161 PMID:24586912

Patent foramen ovale closure with GORE HELEX or CARDIOFORM Septal Occluder vs. antiplatelet therapy for reduction of recurrent stroke or new brain infarct in patients with prior cryptogenic stroke: Design of the randomized Gore REDUCE Clinical Study.

PubMed

Kasner, Scott E; Thomassen, Lars; Søndergaard, Lars; Rhodes, John F; Larsen, Coby C; Jacobson, Joth

2017-12-01

Rationale The utility of patent foramen ovale (PFO) closure for secondary prevention in patients with prior cryptogenic stroke is uncertain despite multiple randomized trials completed to date. Aims The Gore REDUCE Clinical Study (REDUCE) aims to establish superiority of patent foramen ovale closure in conjunction with antiplatelet therapy over antiplatelet therapy alone in reducing the risk of recurrent clinical ischemic stroke or new silent brain infarct in patients who have had a cryptogenic stroke. Methods and design This controlled, open-label trial randomized 664 subjects with cryptogenic stroke at 63 multinational sites in a 2:1 ratio to either antiplatelet therapy plus patent foramen ovale closure (with GORE® HELEX® Septal Occluder or GORE® CARDIOFORM Septal Occluder) or antiplatelet therapy alone. Subjects will be prospectively followed for up to five years. Neuroimaging is required for all subjects at baseline and at two years or study exit. Study outcomes The two co-primary endpoints for the study are freedom from recurrent clinical ischemic stroke through at least 24 months post-randomization and incidence of new brain infarct (defined as clinical ischemic stroke or silent brain infarct) through 24 months. The primary analyses are an unadjusted log-rank test and a binomial test of subject-based proportions, respectively, both on the intent-to-treat population, with adjustment for testing multiplicity. Discussion The REDUCE trial aims to target a patient population with truly cryptogenic strokes. Medical therapy is limited to antiplatelet agents in both arms thereby reducing confounding. The trial should determine whether patent foramen ovale closure with the Gore septal occluders is safe and more effective than medical therapy alone for the prevention of recurrent clinical ischemic stroke or new silent brain infarct; the neuroimaging data will provide an opportunity to further support the proof of concept. The main results are anticipated in 2017. Registration Clinical trial registration-URL: http://clinicaltrials.gov/show/NCT00738894.

Continuous Passive Motion Provides Good Pain Control in Patients with Adhesive Capsulitis

ERIC Educational Resources Information Center

Dundar, Umit; Toktas, Hasan; Cakir, Tuncay; Evcik, Deniz; Kavuncu, Vural

2009-01-01

Painful stiffening of the shoulder, "frozen shoulder" is a common cause of shoulder pain and disability. Continuous passive motion (CPM) is an established method of preventing joint stiffness and of overcoming it. A randomized, comparative prospective clinical trial was planned to compare the early response with different rehabilitation…

Early Behavioral Intervention Is Associated with Normalized Brain Activity in Young Children with Autism

ERIC Educational Resources Information Center

Dawson, Geraldine; Jones, Emily J. H.; Merkle, Kristen; Venema, Kaitlin; Lowy, Rachel; Faja, Susan; Kamara, Dana; Murias, Michael; Greenson, Jessica; Winter, Jamie; Smith, Milani; Rogers, Sally J.; Webb, Sara J.

2012-01-01

Objective: A previously published randomized clinical trial indicated that a developmental behavioral intervention, the Early Start Denver Model (ESDM), resulted in gains in IQ, language, and adaptive behavior of children with autism spectrum disorder. This report describes a secondary outcome measurement from this trial, EEG activity. Method:…

Cognitive-Behavioral Therapy to Promote Smoking Cessation among African American Smokers: A Randomized Clinical Trial

ERIC Educational Resources Information Center

Webb, Monica S.; de Ybarra, Denise Rodriguez; Baker, Elizabeth A.; Reis, Isildinha M.; Carey, Michael P.

2010-01-01

Objective: The health consequences of tobacco smoking disproportionately affect African Americans, but research on whether efficacious interventions can be generalized to this population is limited. This study examined the efficacy of group-based cognitive-behavioral therapy (CBT) for smoking cessation among African Americans. Method: Participants…

Motivating Latino Caregivers of Children with Asthma to Quit Smoking: A Randomized Trial

ERIC Educational Resources Information Center

Borrelli, Belinda; McQuaid, Elizabeth L.; Novak, Scott P.; Hammond, S. Katharine; Becker, Bruce

2010-01-01

Objective: Secondhand smoke exposure is associated with asthma onset and exacerbation. Latino children have higher rates of asthma morbidity than other groups. The current study compared the effectiveness of a newly developed smoking cessation treatment with existing clinical guidelines for smoking cessation. Method: Latino caregivers who smoked…

Implementing Cognitive Behavioral Therapy for Chronic Fatigue Syndrome in a Mental Health Center: A Benchmarking Evaluation

ERIC Educational Resources Information Center

Scheeres, Korine; Wensing, Michel; Knoop, Hans; Bleijenberg, Gijs

2008-01-01

Objective: This study evaluated the success of implementing cognitive behavioral therapy (CBT) for chronic fatigue syndrome (CFS) in a representative clinical practice setting and compared the patient outcomes with those of previously published randomized controlled trials (RCTs) of CBT for CFS. Method: The implementation interventions were the…

Within-Group Effect-Size Benchmarks for Trauma-Focused Cognitive Behavioral Therapy with Children and Adolescents

ERIC Educational Resources Information Center

Rubin, Allen; Washburn, Micki; Schieszler, Christine

2017-01-01

Purpose: This article provides benchmark data on within-group effect sizes from published randomized clinical trials (RCTs) supporting the efficacy of trauma-focused cognitive behavioral therapy (TF-CBT) for traumatized children. Methods: Within-group effect-size benchmarks for symptoms of trauma, anxiety, and depression were calculated via the…

The Sun Sense Study: An Intervention to Improve Sun Protection in Children

ERIC Educational Resources Information Center

Glasser, Alice; Shaheen, Magda; Glenn, Beth A.; Bastani, Roshan

2010-01-01

Objectives: To assess the effect of a multicomponent intervention on parental knowledge, sun avoidance behaviors, and sun protection practices in children 3-10 years. Methods: A randomized trial at a pediatric clinic recruited 197 caregiver-child pairs (90% parents). Intervention included a brief presentation and brochure for the parent and…

Anesthetic Efficacy of Meperidine in Teeth With Symptomatic Irreversible Pulpitis

PubMed Central

Mohajeri, Ladan; Salehi, Farnaz; Mehrvarzfar, Payman; Arfaee, Hamide; Bohluli, Behnam; Hamedy, Reza

2015-01-01

Achieving adequate pulpal anesthesia in mandibular teeth is always a challenge. Supplementary injections and using drugs in combination are some methods implemented to overcome this hurdle. In this randomized clinical trial, use of meperidine in conjunction with lidocaine in intraligamentary injection did not exhibit significant improvement in anesthesia. PMID:25849469

Functioning and Quality of Life in the Treatment for Adolescents with Depression Study (TADS)

ERIC Educational Resources Information Center

Vitiello, Benedetto; Rohde, Paul; Silva, Susan; Wells, Karen; Casat, Charles; Waslick, Bruce; Simons, Anne; Reinecke, Mark; Weller, Elizabeth; Kratochvil, Christopher; Walkup, John; Pathak, Sanjeev; Robins, Michele; March, John

2006-01-01

Obective: To test whether 12-week treatment of major depression improved the level of functioning, global health, and quality of life of adolescents. Method: The Treatment for Adolescents With Depression Study was a multisite, randomized clinical trial of fluoxetine, cognitive-behavioral therapy (CBT), their combination (COMB), or clinical…

Predictors and Moderators of Acute Outcome in the Treatment for Adolescents with Depression Study (TADS)

ERIC Educational Resources Information Center

Curry, John; Rohde, Paul; Simons, Anne; Silva, Susan; Vitiello, Benedetto; Kratochvil, Christopher; Reinecke, Mark; Feeny, Norah; Wells, Karen; Pathak, Sanjeev; Weller, Elizabeth; Rosenberg, David; Kennard, Betsy; Robins, Michele; Ginsburg, Golda; March, John

2006-01-01

Objective: To identify predictors and moderators of response to acute treatments among depressed adolescents (N = 439) randomly assigned to fluoxetine, cognitive-behavioral therapy (CBT), both fluoxetine and CBT, or clinical management with pill placebo in the Treatment for Adolescents With Depression Study (TADS). Method: Potential baseline…

Data entry errors and design for model-based tight glycemic control in critical care.

PubMed

Ward, Logan; Steel, James; Le Compte, Aaron; Evans, Alicia; Tan, Chia-Siong; Penning, Sophie; Shaw, Geoffrey M; Desaive, Thomas; Chase, J Geoffrey

2012-01-01

Tight glycemic control (TGC) has shown benefits but has been difficult to achieve consistently. Model-based methods and computerized protocols offer the opportunity to improve TGC quality but require human data entry, particularly of blood glucose (BG) values, which can be significantly prone to error. This study presents the design and optimization of data entry methods to minimize error for a computerized and model-based TGC method prior to pilot clinical trials. To minimize data entry error, two tests were carried out to optimize a method with errors less than the 5%-plus reported in other studies. Four initial methods were tested on 40 subjects in random order, and the best two were tested more rigorously on 34 subjects. The tests measured entry speed and accuracy. Errors were reported as corrected and uncorrected errors, with the sum comprising a total error rate. The first set of tests used randomly selected values, while the second set used the same values for all subjects to allow comparisons across users and direct assessment of the magnitude of errors. These research tests were approved by the University of Canterbury Ethics Committee. The final data entry method tested reduced errors to less than 1-2%, a 60-80% reduction from reported values. The magnitude of errors was clinically significant and was typically by 10.0 mmol/liter or an order of magnitude but only for extreme values of BG < 2.0 mmol/liter or BG > 15.0-20.0 mmol/liter, both of which could be easily corrected with automated checking of extreme values for safety. The data entry method selected significantly reduced data entry errors in the limited design tests presented, and is in use on a clinical pilot TGC study. The overall approach and testing methods are easily performed and generalizable to other applications and protocols. © 2012 Diabetes Technology Society.

Machine Learning Techniques for Prediction of Early Childhood Obesity.

PubMed

Dugan, T M; Mukhopadhyay, S; Carroll, A; Downs, S

2015-01-01

This paper aims to predict childhood obesity after age two, using only data collected prior to the second birthday by a clinical decision support system called CHICA. Analyses of six different machine learning methods: RandomTree, RandomForest, J48, ID3, Naïve Bayes, and Bayes trained on CHICA data show that an accurate, sensitive model can be created. Of the methods analyzed, the ID3 model trained on the CHICA dataset proved the best overall performance with accuracy of 85% and sensitivity of 89%. Additionally, the ID3 model had a positive predictive value of 84% and a negative predictive value of 88%. The structure of the tree also gives insight into the strongest predictors of future obesity in children. Many of the strongest predictors seen in the ID3 modeling of the CHICA dataset have been independently validated in the literature as correlated with obesity, thereby supporting the validity of the model. This study demonstrated that data from a production clinical decision support system can be used to build an accurate machine learning model to predict obesity in children after age two.

Biodegradable implants versus standard metal fixation for displaced radial head fractures. A prospective, randomized, multicenter study.

PubMed

Helling, Hanns-Joachim; Prokop, Axel; Schmid, Hans Ulrich; Nagel, Michael; Lilienthal, Jürgen; Rehm, Klaus Emil

2006-01-01

This multicenter, prospective, randomized study compares the use of biodegradable polylactide pins with standard metal mini-fragment implants for the treatment of displaced radial head fractures. It compares complication rates and clinical outcomes of both treatment methods. At 2 years, 135 (82%) of 164 patients were available for evaluation. Equivalence of treatment method was defined as a difference of 10% or less in the number of complication-free patients. Functional status was assessed by using the Broberg and Morrey Elbow Score and compared by an unpaired t test. Good or excellent clinical results were achieved by 92% (56/61) of the control patients and 96% (71/74) of the polylactide patients. The incidence of complication-free patients was 3.7% less in the polylactide group than in the control group. The 1-sided 95% confidence interval for the treatment difference between the 2 groups was more than -6.1%. Biodegradable polylactide pins have at least comparable outcomes as standard metal implants for the internal fixation of reconstructable displaced radial head fractures.

Use of antimicrobial drugs in general hospitals. I. Description of population and definition of methods.

PubMed

Townsend, T R; Shapiro, M; Rosner, B; Kass, E H

1979-06-01

The patterns of use of antimicrobial drugs in a random sample of general hosptials in Pennsylvania were studied. The sample was tested for validity, and all deaths and discharges were analyzed for 10 random days drawn across the year spanning July 1973 to June 1974. Methods were developed for abstracting the hospital records and for determining the reproducibility of the findings of the physician and nonphysician chart reviewers. More than 99% of the requested charts were available. In the 5,288 charts reviewed, most of the required data were readily available. The study population was 84% white and 58% female; most patients were in hospitals that had more than 300 beds and that were located in towns with populations of greater than 10,000. In 41% of the 2,070 antimicrobial courses administered to almost 30% of the patients, an explicit clinical statement of why the drug was being given could be found in the chart. The information for review was found in clinical charts, but in half of the charts, the information required was not on face sheets and discharge summaries.

Treatment of chronic pain associated with nocturnal bruxism with botulinum toxin. A prospective and randomized clinical study

PubMed Central

Al-Wayli, Hessa

2017-01-01

Background To evaluate the role of botulinum toxin type A (BTX-A) in the treatment of pain associated with nocturnal bruxism. Material and Methods Fifty subjects reporting nocturnal bruxism were recruited for a randomized clinical trial. Twenty five bruxers were injected with botulinum toxin in both masseters, and twenty five were treated with traditional methods of treating bruxism. Patients were evaluated at 3rd week, 2nd and 6th month and one year after injection and then used to calculate bruxism events. Bruxism symptoms were investigated using questionnaires. Results Mean pain score due to Bruxism events in the masseter muscle decreased significantly in the botulinum toxin injection group A (P =0.000, highly significant). However, in the conventional treatment group, mean pain score does not show improvement with time (p>0.05). Conclusions Our results suggest that botulinum toxin injection reduced the mean pain score and number of bruxism events, most likely by decreasing the muscle activity of masseter rather than affecting the central nervous system. Key words:Temporomandibular pain, nocturnal bruxism, botulinum toxin. PMID:28149474

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.

Colorectal adenoma recurrence rates among post-polypectomy patients in the placebo-controlled groups of randomized clinical trials: a meta-analysis

PubMed Central

Shi, Xin; Yang, Zhiping; Wu, Qiong; Fan, Daiming

2017-01-01

Background Evidence regarding the benefit of therapy to prevent the post-polypectomy recurrence of colorectal adenoma is limited. Endoscopic recurrence is the main outcome according to an evaluation of trials involving recurrence prevention. Aim To estimate the recurrence rates of post-polypectomy colorectal adenoma in placebo-controlled arms of randomized clinical trials and to identify the prognostic factors influencing these rates. Methods We combined data from all randomized controlled trials evaluating therapies for colorectal adenoma using placebo from 1988 to 2016. The data were combined in a random-effects model. Primary outcomes were endoscopic adenoma and advanced adenoma recurrence of colorectal adenoma. Results The pooled estimates of the adenoma recurrence rates were 37% (95% confidence interval [CI], 33%-41%; range, 33%-52%) at 1 year, 47% (95% CI, 41%-54%; range, 46%-51%) at 2 years, 41% (95% CI, 33%-48%; range, 20%-61%) at 3 years, 48% (95% CI, 38%-57%; range, 37%-53%) at 4 years, and 60% (95% CI, 52%-68%; range, 48%-68%) at 5 years. The pooled estimates of the advanced adenoma recurrence rates were 10% (95% CI, 6%-15%; range, 7%-13%) at 1 year, 12% (95% CI, 8%-16%; range, 3%-19%) at 3 years, 14% (95% CI, 10%-18%; range, 13%-16%) at 4 years, and 14% (95% CI, 10%-19%; range, 9%-21%) at 5 years. Significant heterogeneity among the randomized clinical trials (P < 0.001) was observed for each recurrence rate. Conclusions This meta-analysis confirms the heterogeneity of recurrence rates among post-polypectomy colorectal adenoma patients who received placebo. No single design variable was identified that might explain the heterogeneity. PMID:28977952

Randomized Controlled Trial of Pancreaticojejunostomy versus Stapler Closure of the Pancreatic Stump During Distal Pancreatectomy to Reduce Pancreatic Fistula

PubMed Central

Kawai, Manabu; Hirono, Seiko; Okada, Ken-ichi; Sho, Masayuki; Nakajima, Yoshiyuki; Eguchi, Hidetoshi; Nagano, Hiroaki; Ikoma, Hisashi; Morimura, Ryou; Takeda, Yutaka; Nakahira, Shin; Suzumura, Kazuhiro; Fujimoto, Jiro; Yamaue, Hiroki

2016-01-01

Objectives: The aim of this study was to evaluate in a multicenter randomized controlled trial (RCT) whether pancreaticojejunostomy (PJ) of pancreatic stump decreases the incidence of pancreatic fistula after distal pancreatectomy (DP) compared with stapler closure. Background: Several studies reported that PJ of pancreatic stump reduces the incidence of pancreatic fistula after DP. However, no RCT has confirmed the efficacy of PJ of pancreatic stump. Methods: One hundred thirty-six patients scheduled for DP were enrolled in this study between June 2011 and March 2014 at 6 high-volume surgical centers in Japan. Enrolled patients were randomized to either stapler closure or PJ. The primary endpoint was the incidence of pancreatic fistula based on the International Study Group on Pancreatic Fistula criteria. This RCT was registered with ClinicalTrials.gov (NCT01384617). Results: Sixty-one patients randomized to stapler and 62 patients randomized to PJ were analyzed by intention-to-treat. Pancreatic fistula occurred in 23 patients (37.7%) in the stapler closure group and 24 (38.7%) in the PJ group (P = 0.332) in intention-to-treat analysis. The incidence of clinically relevant pancreatic fistula (grade B or C) was 16.4% for stapler closure and 9.7% for PJ (P = 0.201). Mortality was zero in both groups. In a subgroup analysis for thickness of pancreas greater than 12 mm, the incidence of clinically relevant pancreatic fistula occurred in 22.2% of the patients in the stapler closure group and in 6.2% of the PJ group (P = 0.080). Conclusions: PJ of the pancreatic stump during DP does not reduce pancreatic fistula compared with stapler closure. PMID:26473652

Patient satisfaction with different interpreting methods: a randomized controlled trial.

PubMed

Gany, Francesca; Leng, Jennifer; Shapiro, Ephraim; Abramson, David; Motola, Ivette; Shield, David C; Changrani, Jyotsna

2007-11-01

Growth of the foreign-born population in the U.S. has led to increasing numbers of limited-English-proficient (LEP) patients. Innovative medical interpreting strategies, including remote simultaneous medical interpreting (RSMI), have arisen to address the language barrier. This study evaluates the impact of interpreting method on patient satisfaction. 1,276 English-, Spanish-, Mandarin-, and Cantonese-speaking patients attending the primary care clinic and emergency department of a large New York City municipal hospital were screened for enrollment in a randomized controlled trial. Language-discordant patients were randomized to RSMI or usual and customary (U&C) interpreting. Patients with language-concordant providers received usual care. Demographic and patient satisfaction questionnaires were administered to all participants. 541 patients were language-concordant with their providers and not randomized; 371 were randomized to RSMI, 167 of whom were exposed to RSMI; and 364 were randomized to U&C, 198 of whom were exposed to U&C. Patients randomized to RSMI were more likely than those with U&C to think doctors treated them with respect (RSMI 71%, U&C 64%, p < 0.05), but they did not differ in other measures of physician communication/care. In a linear regression analysis, exposure to RSMI was significantly associated with an increase in overall satisfaction with physician communication/care (beta 0.10, 95% CI 0.02-0.18, scale 0-1.0). Patients randomized to RSMI were more likely to think the interpreting method protected their privacy (RSMI 51%, U&C 38%, p < 0.05). Patients randomized to either arm of interpretation reported less comprehension and satisfaction than patients in language-concordant encounters. While not a substitute for language-concordant providers, RSMI can improve patient satisfaction and privacy among LEP patients. Implementing RSMI should be considered an important component of a multipronged approach to addressing language barriers in health care.

A Randomized Controlled Trial Comparing the McKenzie Method to Motor Control Exercises in People With Chronic Low Back Pain and a Directional Preference.

PubMed

Halliday, Mark H; Pappas, Evangelos; Hancock, Mark J; Clare, Helen A; Pinto, Rafael Z; Robertson, Gavin; Ferreira, Paulo H

2016-07-01

Study Design Randomized clinical trial. Background Motor control exercises are believed to improve coordination of the trunk muscles. It is unclear whether increases in trunk muscle thickness can be facilitated by approaches such as the McKenzie method. Furthermore, it is unclear which approach may have superior clinical outcomes. Objectives The primary aim was to compare the effects of the McKenzie method and motor control exercises on trunk muscle recruitment in people with chronic low back pain classified with a directional preference. The secondary aim was to conduct a between-group comparison of outcomes for pain, function, and global perceived effect. Methods Seventy people with chronic low back pain who demonstrated a directional preference using the McKenzie assessment were randomized to receive 12 treatments over 8 weeks with the McKenzie method or with motor control approaches. All outcomes were collected at baseline and at 8-week follow-up by blinded assessors. Results No significant between-group difference was found for trunk muscle thickness of the transversus abdominis (-5.8%; 95% confidence interval [CI]: -15.2%, 3.7%), obliquus internus (-0.7%; 95% CI: -6.6%, 5.2%), and obliquus externus (1.2%; 95% CI: -4.3%, 6.8%). Perceived recovery was slightly superior in the McKenzie group (-0.8; 95% CI: -1.5, -0.1) on a -5 to +5 scale. No significant between-group differences were found for pain or function (P = .99 and P = .26, respectively). Conclusion We found no significant effect of treatment group for trunk muscle thickness. Participants reported a slightly greater sense of perceived recovery with the McKenzie method than with the motor control approach. Level of Evidence Therapy, level 1b-. Registered September 7, 2011 at www.anzctr.org.au (ACTRN12611000971932). J Orthop Sports Phys Ther 2016;46(7):514-522. Epub 12 May 2016. doi:10.2519/jospt.2016.6379.

Child/Adolescent Anxiety Multimodal Study (CAMS): rationale, design, and methods

PubMed Central

2010-01-01

Objective To present the design, methods, and rationale of the Child/Adolescent Anxiety Multimodal Study (CAMS), a recently completed federally-funded, multi-site, randomized placebo-controlled trial that examined the relative efficacy of cognitive-behavior therapy (CBT), sertraline (SRT), and their combination (COMB) against pill placebo (PBO) for the treatment of separation anxiety disorder (SAD), generalized anxiety disorder (GAD) and social phobia (SoP) in children and adolescents. Methods Following a brief review of the acute outcomes of the CAMS trial, as well as the psychosocial and pharmacologic treatment literature for pediatric anxiety disorders, the design and methods of the CAMS trial are described. Results CAMS was a six-year, six-site, randomized controlled trial. Four hundred eighty-eight (N = 488) children and adolescents (ages 7-17 years) with DSM-IV-TR diagnoses of SAD, GAD, or SoP were randomly assigned to one of four treatment conditions: CBT, SRT, COMB, or PBO. Assessments of anxiety symptoms, safety, and functional outcomes, as well as putative mediators and moderators of treatment response were completed in a multi-measure, multi-informant fashion. Manual-based therapies, trained clinicians and independent evaluators were used to ensure treatment and assessment fidelity. A multi-layered administrative structure with representation from all sites facilitated cross-site coordination of the entire trial, study protocols and quality assurance. Conclusions CAMS offers a model for clinical trials methods applicable to psychosocial and psychopharmacological comparative treatment trials by using state-of-the-art methods and rigorous cross-site quality controls. CAMS also provided a large-scale examination of the relative and combined efficacy and safety of the best evidenced-based psychosocial (CBT) and pharmacologic (SSRI) treatments to date for the most commonly occurring pediatric anxiety disorders. Primary and secondary results of CAMS will hold important implications for informing practice-relevant decisions regarding the initial treatment of youth with anxiety disorders. Trial registration ClinicalTrials.gov NCT00052078. PMID:20051130

Volume calculation of CT lung lesions based on Halton low-discrepancy sequences

NASA Astrophysics Data System (ADS)

Li, Shusheng; Wang, Liansheng; Li, Shuo

2017-03-01

Volume calculation from the Computed Tomography (CT) lung lesions data is a significant parameter for clinical diagnosis. The volume is widely used to assess the severity of the lung nodules and track its progression, however, the accuracy and efficiency of previous studies are not well achieved for clinical uses. It remains to be a challenging task due to its tight attachment to the lung wall, inhomogeneous background noises and large variations in sizes and shape. In this paper, we employ Halton low-discrepancy sequences to calculate the volume of the lung lesions. The proposed method directly compute the volume without the procedure of three-dimension (3D) model reconstruction and surface triangulation, which significantly improves the efficiency and reduces the complexity. The main steps of the proposed method are: (1) generate a certain number of random points in each slice using Halton low-discrepancy sequences and calculate the lesion area of each slice through the proportion; (2) obtain the volume by integrating the areas in the sagittal direction. In order to evaluate our proposed method, the experiments were conducted on the sufficient data sets with different size of lung lesions. With the uniform distribution of random points, our proposed method achieves more accurate results compared with other methods, which demonstrates the robustness and accuracy for the volume calculation of CT lung lesions. In addition, our proposed method is easy to follow and can be extensively applied to other applications, e.g., volume calculation of liver tumor, atrial wall aneurysm, etc.

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.

The use of electronic medical records for recruitment in clinical trials: findings from the Lifestyle Intervention for Treatment of Diabetes trial.

PubMed

Effoe, Valery S; Katula, Jeffrey A; Kirk, Julienne K; Pedley, Carolyn F; Bollhalter, Linda Y; Brown, W Mark; Savoca, Margaret R; Jones, Stedman T; Baek, Janet; Bertoni, Alain G

2016-10-13

The use of the electronic medical record (EMR) system in recruitment in clinical trials has the potential for providing a very reliable and cost-effective recruiting methodology which may improve participant recruitment in clinical trials. We examined a recruitment approach centered on the use of the EMR, as well as other traditional methods, in the Lifestyle Intervention for Treatment of Diabetes (LIFT Diabetes) trial. LIFT Diabetes is a randomized controlled trial designed to investigate the effects of two contrasting interventions on cardiovascular disease risk: a community-based intensive lifestyle program aimed at achieving weight loss and a clinic-based enhanced diabetes self-management program. Eligible participants were overweight/obese (body mass index, BMI ≥25 kg/m 2 ) patients with type 2 diabetes who were aged 21 years or older. Recruitment strategies included the use of the EMR system (primary), direct referrals, media advertisements, and community screenings. A total of 1102 telephone screens were conducted, resulting in randomization of 260 participants (61.5 % from EMR, mean age 56.3 years, 66.2 % women, 48.1 % non-Hispanic blacks) over a 21-month period, with a yield of 23.6 %. Recruitment yields differed by recruitment method, with referrals having the highest yield (27.5 %). A history of cardiovascular disease was the main health reason for exclusion from the study (16.5 %). An additional 8.9 % were excluded for BMI <25 kg/m 2 (<27 kg/m 2 for insulin users), 5.4 % could not exercise, 5.2 % had an HbA1c >11 %, and 34.9 % were excluded for other non-medical reasons. Exclusion criteria did not appear to differentially affect enrollment in terms of race or ethnicity. Future clinical studies should tailor their recruitment strategies based on the participant demographics of interest. Efficient methods such as using the EMR system and referrals should be prioritized over labor-intensive, low-yielding methods such as community screenings and mass mailings. ClinicalTrials.gov: NCT01806727 . Registered on 5 March 2013.

Feasibility of Extracting Key Elements from ClinicalTrials.gov to Support Clinicians' Patient Care Decisions.

PubMed

Kim, Heejun; Bian, Jiantao; Mostafa, Javed; Jonnalagadda, Siddhartha; Del Fiol, Guilherme

2016-01-01

Motivation: Clinicians need up-to-date evidence from high quality clinical trials to support clinical decisions. However, applying evidence from the primary literature requires significant effort. Objective: To examine the feasibility of automatically extracting key clinical trial information from ClinicalTrials.gov. Methods: We assessed the coverage of ClinicalTrials.gov for high quality clinical studies that are indexed in PubMed. Using 140 random ClinicalTrials.gov records, we developed and tested rules for the automatic extraction of key information. Results: The rate of high quality clinical trial registration in ClinicalTrials.gov increased from 0.2% in 2005 to 17% in 2015. Trials reporting results increased from 3% in 2005 to 19% in 2015. The accuracy of the automatic extraction algorithm for 10 trial attributes was 90% on average. Future research is needed to improve the algorithm accuracy and to design information displays to optimally present trial information to clinicians.

Gender Research in the National Institute on Drug Abuse National Treatment Clinical Trials Network: A Summary of Findings

PubMed Central

Greenfield, Shelly F.; Rosa, Carmen; Putnins, Susan I.; Green, Carla A.; Brooks, Audrey J.; Calsyn, Donald A.; Cohen, Lisa R.; Erickson, Sarah; Gordon, Susan M.; Haynes, Louise; Killeen, Therese; Miele, Gloria; Tross, Susan; Winhusen, Theresa

2011-01-01

Background The NIDA National Drug Abuse Treatment Clinical Trials Network (CTN) was established to foster translation of research into practice in substance abuse treatment settings. The CTN provides a unique opportunity to examine in multi-site, translational clinical trials, the outcomes of treatment interventions targeting vulnerable sub-groups of women; the comparative effectiveness of gender-specific protocols to reduce risk behaviors; and gender differences in clinical outcomes. Objectives To review gender-related findings from published CTN clinical trials and related studies from January, 2000 through March, 2010. Methods CTN studies were selected for review if they focused on treatment outcomes or services for special populations of women with substance use disorders (SUDs) including those with trauma histories, pregnancy, co-occurring eating and other psychiatric disorders and HIV risk behaviors; or implemented gender-specific protocols. Results The CTN has randomized 11,500 participants (41% women) across 200 clinics in 24 randomized clinical trials in community settings, of which 4 have been gender-specific. This paper summarizes gender-related findings from CTN clinical trials and related studies, focusing on trauma histories, pregnancy, co-occurring eating and other psychiatric disorders, and HIV risk behaviors. Conclusions These published studies have expanded the evidence base regarding interventions for vulnerable groups of women with SUDs as well as gender-specific interventions to reduce HIV risk behaviors in substance using men and women. The results also underscore the complexity of accounting for gender in the design of clinical trials and analysis of results. Scientific Relevance To fully understand the relevance of gender-specific moderators and mediators of outcome, it is essential that future translational studies adopt more sophisticated approaches to understanding and measuring gender-relevant factors and plan sample sizes that are adequate to support more nuanced analytic methods. PMID:21854272

Effects of Flipped Learning Using Online Materials in a Surgical Nursing Practicum: A Pilot Stratified Group-Randomized Trial

PubMed Central

Lee, Myung Kyung

2018-01-01

Objectives This study examined the effect of flipped learning in comparison to traditional learning in a surgical nursing practicum. Methods The subjects of this study were 102 nursing students in their third year of university who were scheduled to complete a clinical nursing practicum in an operating room or surgical unit. Participants were randomly assigned to either a flipped learning group (n = 51) or a traditional learning group (n = 51) for the 1-week, 45-hour clinical nursing practicum. The flipped-learning group completed independent e-learning lessons on surgical nursing and received a brief orientation prior to the commencement of the practicum, while the traditional-learning group received a face-to-face orientation and on-site instruction. After the completion of the practicum, both groups completed a case study and a conference. The student's self-efficacy, self-leadership, and problem-solving skills in clinical practice were measured both before and after the one-week surgical nursing practicum. Results Participants' independent goal setting and evaluation of beliefs and assumptions for the subscales of self-leadership and problem-solving skills were compared for the flipped learning group and the traditional learning group. The results showed greater improvement on these indicators for the flipped learning group in comparison to the traditional learning group. Conclusions The flipped learning method might offer more effective e-learning opportunities in terms of self-leadership and problem-solving than the traditional learning method in surgical nursing practicums. PMID:29503755

Effectiveness of oncogenetics training on general practitioners' consultation skills: a randomized controlled trial

PubMed Central

Houwink, Elisa J.F.; Muijtjens, Arno M.M.; van Teeffelen, Sarah R.; Henneman, Lidewij; Rethans, Jan Joost; van der Jagt, Liesbeth E.J.; van Luijk, Scheltus J.; Dinant, Geert Jan; van der Vleuten, Cees; Cornel, Martina C.

2014-01-01

Purpose: General practitioners are increasingly called upon to deliver genetic services and could play a key role in translating potentially life-saving advancements in oncogenetic technologies to patient care. If general practitioners are to make an effective contribution in this area, their genetics competencies need to be upgraded. The aim of this study was to investigate whether oncogenetics training for general practitioners improves their genetic consultation skills. Methods: In this pragmatic, blinded, randomized controlled trial, the intervention consisted of a 4-h training (December 2011 and April 2012), covering oncogenetic consultation skills (family history, familial risk assessment, and efficient referral), attitude (medical ethical issues), and clinical knowledge required in primary-care consultations. Outcomes were measured using observation checklists by unannounced standardized patients and self-reported questionnaires. Results: Of 88 randomized general practitioners who initially agreed to participate, 56 completed all measurements. Key consultation skills significantly and substantially improved; regression coefficients after intervention were equivalent to 0.34 and 0.28 at 3-month follow-up, indicating a moderate effect size. Satisfaction and perceived applicability of newly learned skills were highly scored. Conclusion: The general practitioner–specific training proved to be a feasible, satisfactory, and clinically applicable method to improve oncogenetics consultation skills and could be used as an educational framework to inform future training activities with the ultimate aim of improving medical care. PMID:23722870

Strategies to Support Recruitment of Patients with Life-limiting illness for Research: The Palliative Care Research Cooperative Group

PubMed Central

Hanson, Laura C.; Bull, Janet; Wessell, Kathryn; Massie, Lisa; Bennett, Rachael E.; Kutner, Jean S.; Aziz, Noreen M.; Abernethy, Amy

2014-01-01

Context The Palliative Care Research Cooperative group (PCRC) is the first clinical trials cooperative for palliative care in the United States. Objectives To describe barriers and strategies for recruitment during the inaugural PCRC clinical trial. Methods The parent study was a multi-site randomized controlled trial enrolling adults with life expectancy anticipated to be 1–6 months, randomized to discontinue statins (intervention) vs. to continue on statins (control). To study recruitment best practices, we conducted semi-structured interviews with 18 site Principal Investigators (PI) and Clinical Research Coordinators (CRC), and reviewed recruitment rates. Interviews covered 3 topics – 1) successful strategies for recruitment, 2) barriers to recruitment, and 3) optimal roles of the PI and CRC. Results All eligible site PIs and CRCs completed interviews and provided data on statin protocol recruitment. The parent study completed recruitment of n=381 patients. Site enrollment ranged from 1–109 participants, with an average of 25 enrolled per site. Five major barriers included difficulty locating eligible patients, severity of illness, family and provider protectiveness, seeking patients in multiple settings, and lack of resources for recruitment activities. Five effective recruitment strategies included systematic screening of patient lists, thoughtful messaging to make research relevant, flexible protocols to accommodate patients’ needs, support from clinical champions, and the additional resources of a trials cooperative group. Conclusion The recruitment experience from the multi-site PCRC yields new insights into methods for effective recruitment to palliative care clinical trials. These results will inform training materials for the PCRC and may assist other investigators in the field. PMID:24863152

The Convergence Insufficiency Treatment Trial: Design, Methods, and Baseline Data

PubMed Central

2009-01-01

Objective This report describes the design and methodology of the Convergence Insufficiency Treatment Trial (CITT), the first large-scale, placebo-controlled, randomized clinical trial evaluating treatments for convergence insufficiency (CI) in children. We also report the clinical and demographic characteristics of patients. Methods We prospectively randomized children 9 to 17 years of age to one of four treatment groups: 1) home-based pencil push-ups, 2) home-based computer vergence/accommodative therapy and pencil push-ups, 3) office-based vergence/accommodative therapy with home reinforcement, 4) office-based placebo therapy. Outcome data on the Convergence Insufficiency Symptom Survey (CISS) score (primary outcome), near point of convergence (NPC), and positive fusional vergence were collected after 12 weeks of active treatment and again at 6 and 12 months post-treatment. Results The CITT enrolled 221 children with symptomatic CI with a mean age of 12.0 years (SD = +2.3). The clinical profile of the cohort at baseline was 9Δ exophoria at near (+/− 4.4) and 2Δ exophoria (+/−2.8) at distance, CISS score = 30 (+/−9.0), NPC = 14 cm (+/− 7.5), and near positive fusional vergence break = 13 Δ (+/− 4.6). There were no statistically significant nor clinically relevant differences between treatment groups with respect to baseline characteristics (p > 0.05). Conclusion Hallmark features of the study design include formal definitions of conditions and outcomes, standardized diagnostic and treatment protocols, a placebo treatment arm, masked outcome examinations, and the CISS score outcome measure. The baseline data reported herein define the clinical profile of those enrolled into the CITT. PMID:18300086

A systematic review of clinical outcomes in surgical treatment of adult isthmic spondylolisthesis.

PubMed

Noorian, Shaya; Sorensen, Karen; Cho, Woojin

2018-05-07

A variety of surgical methods are available for the treatment of adult isthmic spondylolisthesis, but there is no consensus regarding their relative effects on clinical outcomes. To compare the effects of different surgical techniques on clinical outcomes in adult isthmic spondylolisthesis. Systematic Review PATIENT SAMPLE: A total of 1,538 patients from six randomized clinical trials and nine observational studies comparing different surgical treatments in adult isthmic spondylolisthesis. Primary outcome measures of interest included differences in pre- versus post-surgical assessments of pain, functional disability, and overall health as assessed by validated pain rating scales and questionnaires. Secondary outcome measures of interest included intraoperative blood loss, length of hospital stay, surgery duration, reoperation rates, and complication rates. A search of the literature was performed in September, 2017 for relevant comparative studies published in the prior 10-year period in the following databases: PubMed, Embase, Web of Science, and ClinicalTrials.Gov. PRISMA guidelines were followed and studies were included/excluded based on strict predetermined criteria. Quality appraisal was conducted using the Newcastle-Ottawa Scale (NOS) for observational studies and the Cochrane Collaboration's risk of bias assessment tool for randomized clinical trials. The authors received no funding support to conduct this review. A total of 15 studies (6 randomized clinical trials and 9 observational studies) were included for full text review, a majority of which only included cases of low-grade isthmic spondylolisthesis. 1 study examined the effects of adding pedicle screw fixation (PS) to posterolateral fusion (PLF) and 2 studies examined the effects of adding reduction to interbody fusion (IF) + PS on clinical outcomes. 5 studies compared PLF, 4 with and 1 without PS, to IF + PS. Additionally, 3 studies compared circumferential fusion (IF + PS + PLF) to IF + PS and 1 study compared circumferential fusion to PLF + PS. 3 studies compared clinical outcomes among different IF + PS techniques (ALIF + PS vs. PLIF + PS vs TLIF + PS) without PLF. As per the Cochrane Collaboration's risk of bias assessment tool, 4 randomized clinical trials had an overall low risk of bias, 1 randomized clinical trial had an unclear risk of bias, and 1 randomized clinical trial had a high risk of bias. As per the Newcastle-Ottawa scale, 3 observational studies were of overall good quality, 4 observational studies were of fair quality, and 2 observational studies were of poor quality. Available studies provide strong evidence that the addition of reduction to fusion does not result in better clinical outcomes of pain and function in low-grade isthmic spondylolisthesis. Evidence also suggests that there is no significant difference between interbody fusion (IF + PS) and posterior fusion (PLF +/- PS) in outcomes of pain, function, and complication rates at follow-up points up to approximately 3 years in cases of low-grade slips. However, studies with longer follow-up points suggest that interbody fusion (IF + PS) may perform better in these same measures at later follow-up points. Available evidence also suggests no difference between circumferential fusion (IF + PS + PLF) and interbody fusion (IF + PS) in outcomes of pain and function in low-grade slips, but circumferential fusion has been associated with greater intraoperative blood loss, longer surgery duration, and longer hospital stays. In terms of clinical outcomes, insufficient evidence is available to assess the utility of adding PS to PLF, the relative efficacy of different interbody fusion (IF + PS) techniques (ALIF + PS vs. TLIF + PS vs. PLIF + PS), and the relative efficacy of circumferential fusion and posterior fusion (PLF + PS). Copyright © 2018. Published by Elsevier Inc.

The role of mineral elements and other chemical compounds used in balneology: data from double-blind randomized clinical trials.

PubMed

Morer, Carla; Roques, Christian-François; Françon, Alain; Forestier, Romain; Maraver, Francisco

2017-12-01

The aims of this study were to conduct a systematic literature review on balneotherapy about the specific therapeutic role of mineral elements and other chemical compounds of mineral waters and derivate peloids/muds and to discuss the study methods used to evaluate it (in musculoskeletal conditions). We searched Medline by PubMed using the following key words: "spa therapy" "balneotherapy" "mud" "peloid" "mud pack Therapy" in combination with "randomized controlled trial" "double blind trial." We also reviewed the reference list of articles retrieved by the Medline search. We selected the double-blind randomized clinical trials that assessed the effects of mineral water or mud treatments compared to tap water, attenuated peloid/mud therapy or similar treatments without the specific minerals or chemical compounds of the treatment group ("non-mineral"). We evaluated the internal validity and the quality of the statistical analysis of these trials. The final selection comprised 27 double-blind randomized clinical trials, 20 related to rheumatology. A total of 1118 patients with rheumatological and other musculoskeletal diseases were evaluated in these studies: 552 of knee osteoarthritis, 47 of hand osteoarthritis, 147 chronic low back pain, 308 of reumathoid arthritis, and 64 of osteoporosis; 293 of these participants were assigned to the experimental groups of knee osteoarthritis, 24 in hand osteoarthritis, 82 of low back pain, 152 with reumathoid arthritis, and 32 with osteoporosis. They were treated with mineral water baths and/or mud/peloid (with or without other forms of treatment, like physical therapy, exercise…). The rest were allocated to the control groups; they received mainly tap water and/or "non-mineral" mud/peloid treatments. Mineral water or mud treatments had better and longer improvements in pain, function, quality of life, clinical parameters, and others in some rheumatologic diseases (knee and hand osteoarthritis, chronic low back pain, rheumatoid arthritis, and osteoporosis) compared to baseline and non-mineral similar treatments. Internal validity and other limitations of the study's methodology impede causal relation of spa therapy on these improvements. Randomized clinical trials are very heterogeneous. Double-blind randomized clinical trials seem to be the key for studying the role of mineral elements and other chemical compounds, observing enough consistency to demonstrate better and longer improvements for mineral waters or derivate compared to tap water; but due to heterogeneity and gaps on study protocol and methodology, existing research is not sufficiently strong to draw firm conclusions. Well-designed studies in larger patients' population are needed to establish the role of minerals and other chemical compounds in spa therapy.

The role of mineral elements and other chemical compounds used in balneology: data from double-blind randomized clinical trials

NASA Astrophysics Data System (ADS)

Morer, Carla; Roques, Christian-François; Françon, Alain; Forestier, Romain; Maraver, Francisco

2017-12-01

The aims of this study were to conduct a systematic literature review on balneotherapy about the specific therapeutic role of mineral elements and other chemical compounds of mineral waters and derivate peloids/muds and to discuss the study methods used to evaluate it (in musculoskeletal conditions). We searched Medline by PubMed using the following key words: "spa therapy" "balneotherapy" "mud" "peloid" "mud pack Therapy" in combination with "randomized controlled trial" "double blind trial." We also reviewed the reference list of articles retrieved by the Medline search. We selected the double-blind randomized clinical trials that assessed the effects of mineral water or mud treatments compared to tap water, attenuated peloid/mud therapy or similar treatments without the specific minerals or chemical compounds of the treatment group ("non-mineral"). We evaluated the internal validity and the quality of the statistical analysis of these trials. The final selection comprised 27 double-blind randomized clinical trials, 20 related to rheumatology. A total of 1118 patients with rheumatological and other musculoskeletal diseases were evaluated in these studies: 552 of knee osteoarthritis, 47 of hand osteoarthritis, 147 chronic low back pain, 308 of reumathoid arthritis, and 64 of osteoporosis; 293 of these participants were assigned to the experimental groups of knee osteoarthritis, 24 in hand osteoarthritis, 82 of low back pain, 152 with reumathoid arthritis, and 32 with osteoporosis. They were treated with mineral water baths and/or mud/peloid (with or without other forms of treatment, like physical therapy, exercise…). The rest were allocated to the control groups; they received mainly tap water and/or "non-mineral" mud/peloid treatments. Mineral water or mud treatments had better and longer improvements in pain, function, quality of life, clinical parameters, and others in some rheumatologic diseases (knee and hand osteoarthritis, chronic low back pain, rheumatoid arthritis, and osteoporosis) compared to baseline and non-mineral similar treatments. Internal validity and other limitations of the study's methodology impede causal relation of spa therapy on these improvements. Randomized clinical trials are very heterogeneous. Double-blind randomized clinical trials seem to be the key for studying the role of mineral elements and other chemical compounds, observing enough consistency to demonstrate better and longer improvements for mineral waters or derivate compared to tap water; but due to heterogeneity and gaps on study protocol and methodology, existing research is not sufficiently strong to draw firm conclusions. Well-designed studies in larger patients' population are needed to establish the role of minerals and other chemical compounds in spa therapy.

Optimization and validation of sample preparation for metagenomic sequencing of viruses in clinical samples.

PubMed

Lewandowska, Dagmara W; Zagordi, Osvaldo; Geissberger, Fabienne-Desirée; Kufner, Verena; Schmutz, Stefan; Böni, Jürg; Metzner, Karin J; Trkola, Alexandra; Huber, Michael

2017-08-08

Sequence-specific PCR is the most common approach for virus identification in diagnostic laboratories. However, as specific PCR only detects pre-defined targets, novel virus strains or viruses not included in routine test panels will be missed. Recently, advances in high-throughput sequencing allow for virus-sequence-independent identification of entire virus populations in clinical samples, yet standardized protocols are needed to allow broad application in clinical diagnostics. Here, we describe a comprehensive sample preparation protocol for high-throughput metagenomic virus sequencing using random amplification of total nucleic acids from clinical samples. In order to optimize metagenomic sequencing for application in virus diagnostics, we tested different enrichment and amplification procedures on plasma samples spiked with RNA and DNA viruses. A protocol including filtration, nuclease digestion, and random amplification of RNA and DNA in separate reactions provided the best results, allowing reliable recovery of viral genomes and a good correlation of the relative number of sequencing reads with the virus input. We further validated our method by sequencing a multiplexed viral pathogen reagent containing a range of human viruses from different virus families. Our method proved successful in detecting the majority of the included viruses with high read numbers and compared well to other protocols in the field validated against the same reference reagent. Our sequencing protocol does work not only with plasma but also with other clinical samples such as urine and throat swabs. The workflow for virus metagenomic sequencing that we established proved successful in detecting a variety of viruses in different clinical samples. Our protocol supplements existing virus-specific detection strategies providing opportunities to identify atypical and novel viruses commonly not accounted for in routine diagnostic panels.

Advice for acute low back pain: a comparison of what research supports and what guidelines recommend.

PubMed

Stevens, Matthew L; Lin, Chung-Wei C; de Carvalho, Flavia A; Phan, Kevin; Koes, Bart; Maher, Chris G

2017-10-01

Advice is widely considered an effective treatment for acute low back pain (LBP); however, details on what and how to deliver this intervention is less clear. We assessed and compared clinical trials that test advice for acute LBP with practice guidelines for their completeness of reporting and concordance on the content, method of delivery, and treatment regimen of advice interventions. Systematic review. Advice randomized controlled trials were identified through a systematic search. Guidelines were taken from recent overviews of guidelines for LBP. Completeness of reporting was assessed using the Template for Intervention Description and Replication checklist. Thematic analysis was used to characterize advice interventions into topics across the aspects of content, method of delivery, and regimen. Concordance between clinical trials and guidelines was assessed by comparing the number of trials that found a statistically significant treatment effect for an intervention that included a specific advice topic with the number of guidelines recommending that topic. The median (interquartile range) completeness of reporting for clinical trials and guidelines was 8 (7-9) and 3 (2-4) out of nine items on the Template for Intervention Description and Replication checklist, respectively. Guideline recommendations were discordant with clinical trials for 50% of the advice topics identified. Completeness of reporting was less than ideal for randomized controlled trials and extremely poor for guidelines. The recommendations made in guidelines of advice for acute LBP were often not concordant with the results of clinical trials. Taken together, these findings mean that the potential clinical value of advice interventions for patients with acute LBP is probably not being realized. Copyright © 2017 Elsevier Inc. All rights reserved.

Increased Patient Enrollment to a Randomized Surgical Trial Through Equipoise Polling of an Expert Surgeon Panel.

PubMed

Ghogawala, Zoher; Schwartz, J Sanford; Benzel, Edward C; Magge, Subu N; Coumans, Jean Valery; Harrington, J Fred; Gelbs, Jared C; Whitmore, Robert G; Butler, William E; Barker, Fred G

2016-07-01

To determine whether patients who learned the views of an expert surgeons' panel's assessment of equipoise between 2 alternative operative treatments had increased likelihood of consenting to randomization. Difficulty obtaining patient consent to randomization is an important barrier to conducting surgical randomized clinical trials, the gold standard for generating clinical evidence. Observational study of the rate of patient acceptance of randomization within a 5-center randomized clinical trial comparing lumbar spinal decompression versus lumbar spinal decompression plus instrumented fusion for patients with symptomatic grade I degenerative lumbar spondylolisthesis with spinal stenosis. Eligible patients were enrolled in the trial and then asked to accept randomization. A panel of 10 expert spine surgeons was formed to review clinical information and images for individual patients to provide an assessment of suitability for randomization. The expert panel vote was disclosed to the patient by the patient's surgeon before the patient decided whether to accept randomization or not. Randomization acceptance among eligible patients without expert panel review was 40% (19/48) compared with 81% (47/58) among patients undergoing expert panel review (P < 0.001). Among expert-reviewed patients, randomization acceptance was 95% when all experts or all except 1 voted for randomization, 75% when 2 experts voted against randomization, and 20% with 3 or 4 votes against (P < 0.001 for trend). Patients provided with an expert panel's assessment of their own suitability for randomization were twice as likely to agree to randomization compared with patients receiving only their own surgeon's recommendation.

[Importance of clinical trial design and standardized implementation in ophthalmology].

PubMed

Xu, Xun

2013-06-01

Clinical trial is an important medical research method, as well as the bridge of translational medicine. The results of scientific evidences are useful to make clinical practice guidelines. At present,much experience of carrying out ophthalmology clinical trials has been obtained and achieved, but there are still some scientific, practical and ethical problems to be solved,because of their impact on the authenticity and reliability of the results. Therefore, attaching great importance to design of the clinical research and implement of the standardization would be the goal and the development direction. Clinical trial design rely on objective, follow international design principles on the ethics,randomization, blinding and placebo setting. During the trial implementation, personnel training,project management and monitoring would help to reduce protocol deviation and ensure data authenticity.

Effectiveness of Nurse-Practitioner-Delivered Brief Motivational Intervention for Young Adult Alcohol and Drug Use in Primary Care in South Africa: A Randomized Clinical Trial

PubMed Central

Mertens, Jennifer R.; Ward, Catherine L.; Bresick, Graham F.; Broder, Tina; Weisner, Constance M.

2014-01-01

Aims: To assess the effectiveness of brief motivational intervention for alcohol and drug use in young adult primary care patients in a low-income population and country. Methods: A randomized controlled trial in a public-sector clinic in Delft, a township in the Western Cape, South Africa recruited 403 patients who were randomized to either single-session, nurse practitioner-delivered Brief Motivational Intervention plus referral list or usual care plus referral list, and followed up at 3 months. Results: Although rates of at-risk alcohol use and drug use did not differ by treatment arm at follow-up, patients assigned to the Brief Motivational Intervention had significantly reduced scores on ASSIST (Alcohol, Smoking and Substance Involvement Screening Test) for alcohol—the most prevalent substance. Conclusion: Brief Motivational Intervention may be effective at reducing at-risk alcohol use in the short term among low-income young adult primary care patients; additional research is needed to examine long-term outcomes. PMID:24899076

Postoperative long-term evaluation of interposition reconstruction compared with Roux-en-Y after total gastrectomy in gastric cancer: prospective randomized controlled trial.

PubMed

Ishigami, Sumiya; Natsugoe, Shoji; Hokita, Shuichi; Aoki, Teruaki; Kashiwagi, Hideyuki; Hirakawa, Kosei; Sawada, Tetsuji; Yamamura, Yoshitaka; Itoh, Seiji; Hirata, Koichi; Ohta, Keiichiro; Mafune, Kenichi; Nakane, Yasushi; Kanda, Tatsuo; Furukawa, Hiroshi; Sasaki, Iwao; Kubota, Tetsuro; Kitajima, Masaki; Aikou, Takashi

2011-09-01

The postoperative clinical superiority of the interposition of jejunum reconstruction (INT) to Roux-en-Y reconstruction (RY) after total gastrectomy has not been clarified. Postoperative quality of life (QOL) was evaluated between the 2 methods by a multi-institutional prospective randomized trial. A total of 103 patients with gastric cancer were prospectively randomly divided into groups for RY (n = 51) or INT reconstruction (n = 52) after total gastrectomy. They were stratified by sex, age, institute, histology, and degree of lymph node dissection. Postoperatively, body mass index (BMI) and nutritional conditions were measured serially, and QOL and postoperative squalor scores were evaluated at 3, 12, and 60 months and compared between the 2 groups. After removing patients who did not complete the follow-up survey or censured cases, 24 patients in the RY group and 18 patients in the INT group were clinically available and their postoperative status was assessed. QOL scores were increased and complication scores were improved in the postoperative periods (P < .01). Postoperative BMI significantly deteriorated compared with preoperative BMI in each group. The postoperative QOL and complication scores at 60 months after surgery were significantly better than those at 3 months after surgery in each group (P < .01). However, there was no significant difference of QOL scores and postoperative complication scores between the 2 reconstruction groups. The nutritional condition in the INT group was nearly the same as that in the RY group. Although our patient sample was small and patients who did not complete the follow-up survey were present, we could not identify any clinical difference between INT and RY after total gastrectomy 60 months after surgery. The safer and simpler RY method may be a more suitable reconstruction method than INT after total gastrectomy. Copyright © 2011. Published by Elsevier Inc.

A randomized, controlled, multicenter contraceptive efficacy clinical trial of the intravas device, a nonocclusive surgical male sterilization.

PubMed

Lu, Wen-Hong; Liang, Xiao-Wei; Gu, Yi-Qun; Wu, Wei-Xiong; Bo, Li-Wei; Zheng, Tian-Gui; Chen, Zhen-Wen

2014-01-01

Because of unavoidable complications of vasectomy, this study was undertaken to assess the efficacy and safety of male sterilization with a nonobstructive intravas device (IVD) implanted into the vas lumen by a mini-surgical method compared with no-scalpel vasectomy (NSV). IVDs were categorized into two types: IVD-B has a tail used for fixing to the vas deferens (fixed wing) whereas IVD-A does not. A multicenter prospective randomized controlled clinical trial was conducted in China. The study was comprised of 1459 male volunteers seeking vasectomy who were randomly assigned to the IVD-A (n = 487), IVD-B (n = 485) or NSV (n = 487) groups and underwent operation. Follow-up included visits at the 3 rd -6 th and 12 th postoperative months. The assessments of the subjects involved regular physical examinations (including general and andrological examinations) and semen analysis. The subjects' partners also underwent monitoring for pregnancy by monthly interviews regarding menstruation and if necessary, urine tests. There were no significant differences in pregnancy rates (0.65% for IVD-A, 0 for IVD-B and 0.21% for NSV) among the three groups (P > 0.05). The cumulative rates of complications at the 12 th postoperative month were zero, 0.9% and 1.7% in the three groups, respectively. In conclusion, IVD male sterilization exhibits a low risk of long-term adverse events and was found to be effective as a male sterilization method, similar to the NSV technique. IVD male sterilization is expected to be a novel contraceptive method.

Informing men about prostate cancer screening: a randomized controlled trial of patient education materials.

PubMed

Ilic, Dragan; Egberts, Kristine; McKenzie, Joanne E; Risbridger, Gail; Green, Sally

2008-04-01

Patient education materials can assist patient decision making on prostate cancer screening. To explore the effectiveness of presenting health information on prostate cancer screening using video, internet, and written interventions on patient decision making, attitudes, knowledge, and screening interest. Randomized controlled trial. A total of 161 men aged over 45, who had never been screened for prostate cancer, were randomized to receive information on prostate cancer screening. Participants were assessed at baseline and 1-week postintervention for decisional conflict, screening interest, knowledge, anxiety, and decision-making preference. A total of 156 men were followed-up at 1-week postintervention. There was no statistical, or clinical, difference in mean change in decisional conflict scores between the 3 intervention groups (video vs internet -0.06 [95% CI -0.24 to 0.12]; video vs pamphlet 0.04 [95%CI -0.15 to 0.22]; internet vs pamphlet 0.10 [95%CI -0.09 to 0.28]). There was also no statistically significant difference in mean knowledge, anxiety, decision-making preference, and screening interest between the 3 intervention groups. Results from this study indicate that there are no clinically significant differences in decisional conflict when men are presented health information on prostate cancer screening via video, written materials, or the internet. Given the equivalence of the 3 methods, other factors need to be considered in deciding which method to use. Health professionals should provide patient health education materials via a method that is most convenient to the patient and their preferred learning style.

Dental Students' Preference with Regard to Tactile or Visual Determination of Injection Site for an Inferior Alveolar Nerve Block in Children: A Crossover Randomized Clinical Trial.

PubMed

Ramazani, Nahid; Iranmanesh, Seyed Masoud

2016-01-01

Instruction of local anesthesia injection in an important part of dental education curricula. This study was performed to compare dental students' preference with regard to tactile or visual determination of injection site for an inferior alveolar nerve block (IANB) in children. This crossover randomized clinical trial was conducted on dental students of Zahedan Dental School who took the first practical course of pediatric dentistry in the first academic semester of 2013-14 (n=42). They were randomly divided into two groups. During the first phase, group I was instructed to find the needle insertion point for an IANB via tactile method and group II was instructed to do it visually. In the second phase, the groups received instructions for the alternate technique. Both instructions were done using live demonstrations by the same instructor and immediately after instruction the learners practiced an IANB using the taught method. A five-point Likert scale questionnaire was then filled out by the students. The preference score was determined by calculating the mean of item scores. Data were analyzed using Mann-Whitney U and Wilcoxon Singed Rank tests in SPSS 19 at P=0.05 level of significance. Thirty-eight students completed the study. By using the visual method to perform an IANB, students gained a significantly higher mean preference score (P=0.020). There was a significant difference in the preference of male students (P=0.008). Instruction of IANB by visual identification of needle insertion point is more desirable by students.

SMART trial: A randomized clinical trial of self-monitoring in behavioral weight management-design and baseline findings

PubMed Central

Burke, Lora E.; Styn, Mindi A.; Glanz, Karen; Ewing, Linda J.; Elci, Okan U.; Conroy, Margaret B.; Sereika, Susan M.; Acharya, Sushama D.; Music, Edvin; Keating, Alison L.; Sevick, Mary Ann

2009-01-01

Background The primary form of treatment for obesity today is behavioral therapy. Self-monitoring diet and physical activity plays an important role in interventions targeting behavior and weight change. The SMART weight loss trial examined the impact of replacing the standard paper record used for self-monitoring with a personal digital assistant (PDA). This paper describes the design, methods, intervention, and baseline sample characteristics of the SMART trial. Methods The SMART trial used a 3-group design to determine the effects of different modes of self-monitoring on short- and long-term weight loss and on adherence to self-monitoring in a 24-month intervention. Participants were randomized to one of three conditions (1) use of a standard paper record (PR); (2) use of a PDA with dietary and physical activity software (PDA); or (3), use of a PDA with the same software plus a customized feedback program (PDA + FB). Results We screened 704 individuals and randomized 210. There were statistically but not clinically significant differences among the three cohorts in age, education, HDL cholesterol, blood glucose and systolic blood pressure. At 24 months, retention rate for the first of three cohorts was 90%. Conclusions To the best of our knowledge, the SMART trial is the first large study to compare different methods of self-monitoring in a behavioral weight loss intervention and to compare the use of PDAs to conventional paper records. This study has the potential to reveal significant details about self-monitoring patterns and whether technology can improve adherence to this vital intervention component. PMID:19665588

Treatment Effect of Drug-Coated Balloons Is Durable to 3 Years in the Femoropopliteal Arteries

PubMed Central

Laird, John R.; Tepe, Gunnar; Brodmann, Marianne; Zeller, Thomas; Scheinert, Dierk; Metzger, Christopher; Micari, Antonio; Sachar, Ravish; Jaff, Michael R.; Wang, Hong; Hasenbank, Melissa S.; Krishnan, Prakash

2018-01-01

Background— Randomized controlled trials have reported favorable 1-year outcomes with drug-coated balloons (DCBs) for the treatment of symptomatic peripheral arterial disease when compared with standard percutaneous transluminal angioplasty (PTA). Evidence remains limited on the durability of the treatment effect with DCBs in the longer term. Methods and Results— IN.PACT SFA is a single-blind, randomized trial (Randomized Trial of IN.PACT Admiral Paclitaxel-Coated Percutaneous Transluminal Angioplasty [PTA] Balloon Catheter vs Standard PTA for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery [SFA] and/or Proximal Popliteal Artery [PPA]) that enrolled 331 patients with symptomatic (Rutherford 2–4) femoropopliteal lesions up to 18 cm in length. Patients were randomized 2:1 to receive treatment with DCB or PTA. The 36-month assessments included primary patency, freedom from clinically driven target lesion revascularization, major adverse events, and functional outcomes. At 36 months, primary patency remained significantly higher among patients treated with DCB compared with PTA (69.5% versus 45.1%; log rank P<0.001). The rates of clinically driven target lesion revascularization were 15.2% and 31.1% (P=0.002) for the DCB and PTA groups, respectively. Functional outcomes were similarly improved between treatment groups even though subjects in the DCB group required significantly fewer reinterventions versus those in the PTA group (P<0.001 for target lesion revascularization, P=0.001 for target vessel revascularization). There were no device- or procedure-related deaths as adjudicated by an independent Clinical Events Committee. Conclusions— Three-year results demonstrate a durable and superior treatment effect among patients treated with DCB versus standard PTA, with significantly higher primary patency and lower clinically driven target lesion revascularization, resulting in similar functional improvements with reduced need for repeat interventions. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01175850 for IN.PACT SFA phase I in the European Union and NCT01566461 for IN.PACT SFA phase II in the United States. PMID:29326153

Text-messaging versus telephone reminders to reduce missed appointments in an academic primary care clinic: a randomized controlled trial

PubMed Central

2013-01-01

Background Telephone or text-message reminders have been shown to significantly reduce the rate of missed appointments in different medical settings. Since text-messaging is less resource-demanding, we tested the hypothesis that text-message reminders would be as effective as telephone reminders in an academic primary care clinic. Methods A randomized controlled non-inferiority trial was conducted in the academic primary care division of the Geneva University Hospitals between November 2010 and April 2011. Patients registered for an appointment at the clinic, and for whom a cell phone number was available, were randomly selected to receive a text-message or a telephone call reminder 24 hours before the planned appointment. Patients were included each time they had an appointment. The main outcome was the rate of unexplained missed appointments. Appointments were not missed if they were cancelled or re-scheduled before or independently from the intervention. We defined non-inferiority as a difference below 2% in the rate of missed appointments and powered the study accordingly. A satisfaction survey was conducted among a random sample of 900 patients (response rate 41%). Results 6450 patients were included, 3285 in the text-message group and 3165 in the telephone group. The rate of missed appointments was similar in the text-message group (11.7%, 95% CI: 10.6-12.8) and in the telephone group (10.2%, 95% CI: 9.2-11.3 p = 0.07). However, only text message reminders were cost-effective. No patient reported any disturbance by any type of reminder in the satisfaction survey. Three quarters of surveyed patients recommended its regular implementation in the clinic. Conclusions Text-message reminders are equivalent to telephone reminders in reducing the proportion of missed appointments in an academic primary care clinic and are more cost-effective. Both types of reminders are well accepted by patients. PMID:23557331

Randomized multicentre trial comparing external and internal pancreatic stenting during pancreaticoduodenectomy.

PubMed

Jang, J-Y; Chang, Y R; Kim, S-W; Choi, S H; Park, S J; Lee, S E; Lim, C-S; Kang, M J; Lee, H; Heo, J S

2016-05-01

There is no consensus on the best method of preventing postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD). This multicentre, parallel group, randomized equivalence trial investigated the effect of two ways of pancreatic stenting after PD on the rate of POPF. Patients undergoing elective PD or pylorus-preserving PD with duct-to-mucosa pancreaticojejunostomy were enrolled from four tertiary referral hospitals. Randomization was stratified according to surgeon with a 1 : 1 allocation ratio to avoid any related technical factors. The primary endpoint was clinically relevant POPF rate. Secondary endpoints were nutritional index, remnant pancreatic volume, long-term complications and quality of life 2 years after PD. A total of 328 patients were randomized to the external (164 patients) or internal (164) stent group between August 2010 and January 2014. The rates of clinically relevant POPF were 24·4 per cent in the external and 18·9 per cent in the internal stent group (risk difference 5·5 per cent). As the 90 per cent confidence interval (-2·0 to 13·0 per cent) did not fall within the predefined equivalence limits (-10 to 10 per cent), the clinically relevant POPF rates in the two groups were not equivalent. Similar results were observed for patients with soft pancreatic texture and high fistula risk score. Other postoperative outcomes were comparable between the two groups. Five stent-related complications occurred in the external stent group. Multivariable analysis revealed that soft pancreatic texture, non-pancreatic disease and high body mass index (23·3 kg/m 2 or above) predicted clinically relevant POPF. External stenting after PD was associated with a higher rate of clinically relevant POPF than internal stenting. Registration number: NCT01023594 (https://www.clinicaltrials.gov). © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

Significance of Random Bladder Biopsies in Non-Muscle Invasive Bladder Cancer

PubMed Central

Kumano, Masafumi; Miyake, Hideaki; Nakano, Yuzo; Fujisawa, Masato

2013-01-01

Background/Aims To evaluate retrospectively the clinical outcome of random bladder biopsies in patients with non-muscle invasive bladder cancer (NMIBC) undergoing transurethral resection (TUR). Patients and Method This study included 234 consecutive patients with NMIBC who underwent random biopsies from normal-appearing urothelium of the bladder, including the anterior wall, posterior wall, right wall, left wall, dome, trigone and/or prostatic urethra, during TUR. Result Thirty-seven patients (15.8%) were diagnosed by random biopsies as having urothelial cancer. Among several factors available prior to TUR, preoperative urinary cytology appeared to be independently related to the detection of urothelial cancer in random biopsies on multivariate analysis. Urinary cytology prior to TUR gave 50.0% sensitivity, 91.7% specificity, 56.8% positive predictive value and 89.3% negative predictive value for predicting the findings of the random biopsies. Conclusion Biopsies of normal-appearing urothelium resulted in the additional detection of urothelial cancer in a definite proportion of NMIBC patients, and it remains difficult to find a reliable alternative to random biopsies. Collectively, these findings suggest that it would be beneficial to perform random biopsies as part of the routine management of NMIBC. PMID:24917759

Comparing the effects of treatment with sildenafil and cognitive-behavioral therapy on treatment of sexual dysfunction in women: a randomized controlled clinical trial

PubMed Central

Omidi, Abdollah; Ahmadvand, Afshin; Najarzadegan, Mohammad Reza; Mehrzad, Fateme

2016-01-01

Background Sexual dysfunction in women is prevalent and common in women after menopause. Many attempts to treat patients with sexual dysfunction by cognitive-behavioral therapy (CBT) methods. But to the best of our knowledge, there has been no study that compared these two methods. Objective The aim of this study was to assess and compare the effects of sildenafil and cognitive-behavioral therapy on treatment of sexual dysfunction in women. Methods In this randomized, controlled, clinical trial, 86 women with arousal and orgasm dysfunction were surveyed. The patients were divided into two groups, i.e., sildenafil and CBT groups. The patients in the sildenafil group were treated by 50 mg of oral sildenafil one hour before intercourse, and the other group had weekly sessions of CBT for eight weeks. Sexual dysfunctions were evaluated by the Female Sexual Function Index (FSFI), a sexual satisfaction questionnaire, and the Enrich marital satisfaction scale. Results The mean age of the participants was 33.14 ± 7.34 years. The mean scores for female sexual function index, sexual satisfaction, and the Enrich marital satisfaction scale were increased in both groups during treatment (p < 0.001). It was found that cognitive-behavioral therapy compared to treatment with sildenafil increased all subscales, except arousal, orgasm, and lubrication. Conclusion Cognitive-behavioral therapy is more effective than treatment with sildenafil for improving female sexual function. Clinical trial registration The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT ID: IRCT2014070318338N1. Funding The authors received no financial support for the research, authorship, and/or publication of this article. PMID:27382439

Investigating the Effect of Extracorporeal Shock Wave Therapy on Reducing Chronic Pain in Patients with Pes Anserine Bursitis: A Randomized, Clinical- Controlled Trial

PubMed Central

Khosrawi, Saeid; Taheri, Parisa; Ketabi, Marziyeh

2017-01-01

Background: Knee pain, is one of the most common causes of patients’ referring to physiatric clinics, and several factors, are involved in its creation. One of these factors is pes anserine bursitis (PAB) for which various treatment methods are used. This study aims to investigate the effect of this method on reducing chronic pain in these patients. Materials and Methods: This clinical trial was conducted in 2013- 2014 on patients with PAB referring to academic, physical medicine clinics. The patients with chronic PAB (pain duration more than 3 months), who were refractory to conservative treatments, were randomly divided into two 20-member experimental groups (extracorporeal shock wave therapy [ESWT] and sham ESWT). Pain scores of all patients were measured using the Visual Analog Scale (VAS) and McGill Pain Questionnaire (MPQ) (total and present pain indexes [TPIs and PPIs]) before intervention, immediately after intervention (3rd week), and after 8 weeks. The pain scores were then compared and statistically analyzed. Results: In the ESWT group, the mean patient pain score of the VAS and TPI in MPQ were significantly lower than in the sham ESWT group immediately after intervention (3rd week): P =0.02, P = 0.04 respectively; and 8 weeks after the end of treatment: P =0.01, P = 0.000. Moreover, the PPI in both groups had significantly decreased over time, although in ESWT group this decrement was significantly more than sham ESWT group (P < 0.001). Conclusion: The results showed that ESWT could be effective in reducing the pain and treating PAB. PMID:28626745

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.

The Inconvenience of Convenience Cohorts: Rhabdomyosarcoma and the PAX-FOXO1 Biomarker

PubMed Central

Rosenberg, Abby R.; Skapek, Stephen X.; Hawkins, Douglas S.

2012-01-01

“Convenience cohorts” comprise individuals thought to represent the general population, but chosen because they are readily available for evaluation, rather than at random. As such, these methods are subject to bias and may be misleading. Convenience cohorts have been used to investigate the prognostic significance of chromosomal translocations between the PAX3 or PAX7 and the FOXO1 genes in rhabdomyosarcoma, the most common pediatric sarcoma. However, retrospective studies assessing the role of PAX-FOXO1 translocations have yielded inconsistent results. This review highlights the findings from several clinical correlation studies of the PAX-FOXO1 biomarker and illustrates the challenges of using such methods to draw clinical conclusions. PMID:22564868

Prediction of In-hospital Mortality in Emergency Department Patients With Sepsis: A Local Big Data–Driven, Machine Learning Approach

PubMed Central

Taylor, R. Andrew; Pare, Joseph R.; Venkatesh, Arjun K.; Mowafi, Hani; Melnick, Edward R.; Fleischman, William; Hall, M. Kennedy

2018-01-01

Objectives Predictive analytics in emergency care has mostly been limited to the use of clinical decision rules (CDRs) in the form of simple heuristics and scoring systems. In the development of CDRs, limitations in analytic methods and concerns with usability have generally constrained models to a preselected small set of variables judged to be clinically relevant and to rules that are easily calculated. Furthermore, CDRs frequently suffer from questions of generalizability, take years to develop, and lack the ability to be updated as new information becomes available. Newer analytic and machine learning techniques capable of harnessing the large number of variables that are already available through electronic health records (EHRs) may better predict patient outcomes and facilitate automation and deployment within clinical decision support systems. In this proof-of-concept study, a local, big data–driven, machine learning approach is compared to existing CDRs and traditional analytic methods using the prediction of sepsis in-hospital mortality as the use case. Methods This was a retrospective study of adult ED visits admitted to the hospital meeting criteria for sepsis from October 2013 to October 2014. Sepsis was defined as meeting criteria for systemic inflammatory response syndrome with an infectious admitting diagnosis in the ED. ED visits were randomly partitioned into an 80%/20% split for training and validation. A random forest model (machine learning approach) was constructed using over 500 clinical variables from data available within the EHRs of four hospitals to predict in-hospital mortality. The machine learning prediction model was then compared to a classification and regression tree (CART) model, logistic regression model, and previously developed prediction tools on the validation data set using area under the receiver operating characteristic curve (AUC) and chi-square statistics. Results There were 5,278 visits among 4,676 unique patients who met criteria for sepsis. Of the 4,222 patients in the training group, 210 (5.0%) died during hospitalization, and of the 1,056 patients in the validation group, 50 (4.7%) died during hospitalization. The AUCs with 95% confidence intervals (CIs) for the different models were as follows: random forest model, 0.86 (95% CI = 0.82 to 0.90); CART model, 0.69 (95% CI = 0.62 to 0.77); logistic regression model, 0.76 (95% CI = 0.69 to 0.82); CURB-65, 0.73 (95% CI = 0.67 to 0.80); MEDS, 0.71 (95% CI = 0.63 to 0.77); and mREMS, 0.72 (95% CI = 0.65 to 0.79). The random forest model AUC was statistically different from all other models (p ≤ 0.003 for all comparisons). Conclusions In this proof-of-concept study, a local big data–driven, machine learning approach outperformed existing CDRs as well as traditional analytic techniques for predicting in-hospital mortality of ED patients with sepsis. Future research should prospectively evaluate the effectiveness of this approach and whether it translates into improved clinical outcomes for high-risk sepsis patients. The methods developed serve as an example of a new model for predictive analytics in emergency care that can be automated, applied to other clinical outcomes of interest, and deployed in EHRs to enable locally relevant clinical predictions. PMID:26679719

The Efficacy and Safety of Shen Guo Lao Nian Granule for Common Cold of Qi-Deficiency Syndrome: Study Protocol for a Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase II Clinical Trial

PubMed Central

Fu, Juanjuan; Ding, Hong; Yang, Haimiao; Huang, Yuhong

2017-01-01

Background Common cold is one of the most frequently occurring illnesses in primary healthcare services and represents considerable disease burden. Common cold of Qi-deficiency syndrome (CCQDS) is an important but less addressed traditional Chinese medicine (TCM) pattern. We designed a protocol to explore the efficacy, safety, and optimal dose of Shen Guo Lao Nian Granule (SGLNG) for treating CCQDS. Methods/Design This is a multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. A total of 240 eligible patients will be recruited from five centers. Patients are randomly assigned to high-dose group, middle-dose group, low-dose group, or control group in a 1 : 1 : 1 : 1 ratio. All drugs are required to be taken 3 times daily for 5 days with a 5-day follow-up period. Primary outcomes are duration of all symptoms, total score reduction on Jackson's scale, and TCM symptoms scale. Secondary outcomes include every single TCM symptom duration and score reduction, TCM main symptoms disappearance rate, curative effects, and comparison between Jackson's scale and TCM symptom scale. Ethics and Trial Registration This study protocol was approved by the Ethics Committee of Clinical Trials and Biomedicine of West China Hospital of Sichuan University (number IRB-2014-12) and registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-15006349). PMID:29430253

Does prolonged β-lactam infusions improve clinical outcomes compared to intermittent infusions? A meta-analysis and systematic review of randomized, controlled trials

PubMed Central

2011-01-01

Background The emergence of multi-drug resistant Gram-negatives (MDRGNs) coupled with an alarming scarcity of new antibiotics has forced the optimization of the therapeutic potential of available antibiotics. To exploit the time above the minimum inhibitory concentration mechanism of β-lactams, prolonging their infusion may improve outcomes. The primary objective of this meta-analysis was to determine if prolonged β-lactam infusion resulted in decreased mortality and improved clinical cure compared to intermittent β-lactam infusion. Methods Relevant studies were identified from searches of MEDLINE, EMBASE, and CENTRAL. Heterogeneity was assessed qualitatively, in addition to I2 and Chi-square statistics. Pooled relative risks (RR) and 95% confidence intervals (CI) were calculated using Mantel-Haenszel random-effects models. Results Fourteen randomized controlled trials (RCTs) were included. Prolonged infusion β-lactams were not associated with decreased mortality (n= 982; RR 0.92; 95% CI:0.61-1.37) or clinical cure (n = 1380; RR 1.00 95% CI:0.94-1.06) compared to intermittent infusions. Subgroup analysis for β-lactam subclasses and equivalent total daily β-lactam doses yielded similar results. Most studies had notable methodological flaws. Conclusions No clinical advantage was observed for prolonged infusion β-lactams. The limited number of studies with MDRGNs precluded evaluation of prolonged infusion of β-lactams for this subgroup. A large, multicenter RCT with critically ill patients infected with MDRGNs is needed. PMID:21696619

A Double-Blind Placebo-Controlled Randomized Clinical Trial With Magnesium Oxide to Reduce Intrafraction Prostate Motion for Prostate Cancer Radiotherapy

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

Lips, Irene M., E-mail: i.m.lips@umcutrecht.nl; Gils, Carla H. van; Kotte, Alexis N.T.J.

2012-06-01

Purpose: To investigate whether magnesium oxide during external-beam radiotherapy for prostate cancer reduces intrafraction prostate motion in a double-blind, placebo-controlled randomized trial. Methods and Materials: At the Department of Radiotherapy, prostate cancer patients scheduled for intensity-modulated radiotherapy (77 Gy in 35 fractions) using fiducial marker-based position verification were randomly assigned to receive magnesium oxide (500 mg twice a day) or placebo during radiotherapy. The primary outcome was the proportion of patients with clinically relevant intrafraction prostate motion, defined as the proportion of patients who demonstrated in {>=}50% of the fractions an intrafraction motion outside a range of 2 mm. Secondarymore » outcome measures included quality of life and acute toxicity. Results: In total, 46 patients per treatment arm were enrolled. The primary endpoint did not show a statistically significant difference between the treatment arms with a percentage of patients with clinically relevant intrafraction motion of 83% in the magnesium oxide arm as compared with 80% in the placebo arm (p = 1.00). Concerning the secondary endpoints, exploratory analyses demonstrated a trend towards worsened quality of life and slightly more toxicity in the magnesium oxide arm than in the placebo arm; however, these differences were not statistically significant. Conclusions: Magnesium oxide is not effective in reducing the intrafraction prostate motion during external-beam radiotherapy, and therefore there is no indication to use it in clinical practice for this purpose.« less

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

Intralesional immunotherapy with tuberculin purified protein derivative (PPD) in recalcitrant wart: A randomized, placebo-controlled, double-blind clinical trial including an extra group of candidates for cryotherapy.

PubMed

Amirnia, Mehdi; Khodaeiani, Effat; Fouladi, Daniel F; Masoudnia, Sima

2016-01-01

Due to paucity of randomized clinical trials, intralesional immunotherapy has not been yet accepted as a standard therapeutic method. To examine the efficacy and safety of intralesional immunotherapy with tuberculin purified protein derivative (PPD) for treating recalcitrant wart. In this randomized, placebo-controlled, double-blind clinical trial, a total of 69 patients with recalcitrant warts received either intralesional PPD antigen (n = 35) or intralesional saline (n = 34) for six times at 2-week intervals. A third group of candidates for cryotherapy (n = 33) was also included. The decrease in lesion size (good: complete response, intermediate: 50-99% improvement, poor: <50% improvement), adverse effects and recurrence within 6-month follow-up were documented. At the final session, good, intermediate and poor responses were observed in 77.1%, 22.9% and 0% of the PPD patients; 0%, 14.7% and 85.3% of the placebo patients and 18.2%, 33.3% and 48.5% of the cryotherapy patients, respectively (PPD versus placebo: p < 0.001; PPD versus cryotherapy: p < 0.001). No significant complication was seen in the PPD group. The recurrence rate was 8.6%, 5.9% and 24.2% in the PPD, placebo and cryotherapy groups, respectively (p > 0.05). Intralesional immunotherapy with PPD antigen is highly effective and safe for treating recalcitrant warts. IRCT201407089844N3 in the Iranian Registry of Clinical Trials (IRCT).

Estimating the optimal dynamic antipsychotic treatment regime: Evidence from the sequential multiple assignment randomized CATIE Schizophrenia Study

PubMed Central

Shortreed, Susan M.; Moodie, Erica E. M.

2012-01-01

Summary Treatment of schizophrenia is notoriously difficult and typically requires personalized adaption of treatment due to lack of efficacy of treatment, poor adherence, or intolerable side effects. The Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) Schizophrenia Study is a sequential multiple assignment randomized trial comparing the typical antipsychotic medication, perphenazine, to several newer atypical antipsychotics. This paper describes the marginal structural modeling method for estimating optimal dynamic treatment regimes and applies the approach to the CATIE Schizophrenia Study. Missing data and valid estimation of confidence intervals are also addressed. PMID:23087488

Randomized, Double-Blind, Placebo-Controlled Study on Decolonization Procedures for Methicillin-Resistant Staphylococcus aureus (MRSA) among HIV-Infected Adults

PubMed Central

Weintrob, Amy; Bebu, Ionut; Agan, Brian; Diem, Alona; Johnson, Erica; Lalani, Tahaniyat; Wang, Xun; Bavaro, Mary; Ellis, Michael; Mende, Katrin; Crum-Cianflone, Nancy

2015-01-01

Background HIV-infected persons have increased risk of MRSA colonization and skin and soft-tissue infections (SSTI). However, no large clinical trial has examined the utility of decolonization procedures in reducing MRSA colonization or infection among community-dwelling HIV-infected persons. Methods 550 HIV-infected adults at four geographically diverse US military HIV clinics were prospectively screened for MRSA colonization at five body locations every 6 months during a 2-year period. Those colonized were randomized in a double-blind fashion to nasal mupirocin (Bactroban) twice daily and hexachlorophene (pHisoHex) soaps daily for 7 days compared to placeboes similar in appearance but without specific antibacterial activity. The primary endpoint was MRSA colonization at 6-months post-randomization; secondary endpoints were time to MRSA clearance, subsequent MRSA infections/SSTI, and predictors for MRSA clearance at the 6-month time point. Results Forty-nine (9%) HIV-infected persons were MRSA colonized and randomized. Among those with 6-month colonization data (80% of those randomized), 67% were negative for MRSA colonization in both groups (p = 1.0). Analyses accounting for missing 6-month data showed no significant differences could have been achieved. In the multivariate adjusted models, randomization group was not associated with 6-month MRSA clearance. The median time to MRSA clearance was similar in the treatment vs. placebo groups (1.4 vs. 1.8 months, p = 0.35). There was no difference on subsequent development of MRSA infections/SSTI (p = 0.89). In a multivariable model, treatment group, demographics, and HIV-specific factors were not predictive of MRSA clearance at the 6-month time point. Conclusion A one-week decolonization procedure had no effect on MRSA colonization at the 6-month time point or subsequent infection rates among community-dwelling HIV-infected persons. More aggressive or novel interventions may be needed to reduce the burden of MRSA in this population. Trial Registration ClinicalTrials.gov NCT00631566 PMID:26018036

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.

Divalproex Sodium for the Treatment of PTSD and Conduct Disordered Youth: A Pilot Randomized Controlled Clinical Trial

ERIC Educational Resources Information Center

Steiner, Hans; Saxena, Kirti S.; Carrion, Victor; Khanzode, Leena A.; Silverman, Melissa; Chang, Kiki

2007-01-01

We examined the efficacy of divalproex sodium (DVP) for the treatment of PTSD in conduct disorder, utilizing a previous study in which 71 youth were enrolled in a randomized controlled clinical trial. Twelve had PTSD. Subjects (all males, mean age 16, SD 1.0) were randomized into high and low dose conditions. Clinical Global Impression (CGI)…

Impact of a Clinical Decision Model for Febrile Children at Risk for Serious Bacterial Infections at the Emergency Department: A Randomized Controlled Trial

PubMed Central

de Vos-Kerkhof, Evelien; Nijman, Ruud G.; Vergouwe, Yvonne; Polinder, Suzanne; Steyerberg, Ewout W.; van der Lei, Johan; Moll, Henriëtte A.; Oostenbrink, Rianne

2015-01-01

Objectives To assess the impact of a clinical decision model for febrile children at risk for serious bacterial infections (SBI) attending the emergency department (ED). Methods Randomized controlled trial with 439 febrile children, aged 1 month-16 years, attending the pediatric ED of a Dutch university hospital during 2010-2012. Febrile children were randomly assigned to the intervention (clinical decision model; n=219) or the control group (usual care; n=220). The clinical decision model included clinical symptoms, vital signs, and C-reactive protein and provided high/low-risks for “pneumonia” and “other SBI”. Nurses were guided by the intervention to initiate additional tests for high-risk children. The clinical decision model was evaluated by 1) area-under-the-receiver-operating-characteristic-curve (AUC) to indicate discriminative ability and 2) feasibility, to measure nurses’ compliance to model recommendations. Primary patient outcome was defined as correct SBI diagnoses. Secondary process outcomes were defined as length of stay; diagnostic tests; antibiotic treatment; hospital admission; revisits and medical costs. Results The decision model had good discriminative ability for both pneumonia (n=33; AUC 0.83 (95% CI 0.75-0.90)) and other SBI (n=22; AUC 0.81 (95% CI 0.72-0.90)). Compliance to model recommendations was high (86%). No differences in correct SBI determination were observed. Application of the clinical decision model resulted in less full-blood-counts (14% vs. 22%, p-value<0.05) and more urine-dipstick testing (71% vs. 61%, p-value<0.05). Conclusions In contrast to our expectations no substantial impact on patient outcome was perceived. The clinical decision model preserved, however, good discriminatory ability to detect SBI, achieved good compliance among nurses and resulted in a more standardized diagnostic approach towards febrile children, with less full blood-counts and more rightfully urine-dipstick testing. Trial Registration Nederlands Trial Register NTR2381 PMID:26024532

Reproducibility of clinical research in critical care: a scoping review.

PubMed

Niven, Daniel J; McCormick, T Jared; Straus, Sharon E; Hemmelgarn, Brenda R; Jeffs, Lianne; Barnes, Tavish R M; Stelfox, Henry T

2018-02-21

The ability to reproduce experiments is a defining principle of science. Reproducibility of clinical research has received relatively little scientific attention. However, it is important as it may inform clinical practice, research agendas, and the design of future studies. We used scoping review methods to examine reproducibility within a cohort of randomized trials examining clinical critical care research and published in the top general medical and critical care journals. To identify relevant clinical practices, we searched the New England Journal of Medicine, The Lancet, and JAMA for randomized trials published up to April 2016. To identify a comprehensive set of studies for these practices, included articles informed secondary searches within other high-impact medical and specialty journals. We included late-phase randomized controlled trials examining therapeutic clinical practices in adults admitted to general medical-surgical or specialty intensive care units (ICUs). Included articles were classified using a reproducibility framework. An original study was the first to evaluate a clinical practice. A reproduction attempt re-evaluated that practice in a new set of participants. Overall, 158 practices were examined in 275 included articles. A reproduction attempt was identified for 66 practices (42%, 95% CI 33-50%). Original studies reported larger effects than reproduction attempts (primary endpoint, risk difference 16.0%, 95% CI 11.6-20.5% vs. 8.4%, 95% CI 6.0-10.8%, P = 0.003). More than half of clinical practices with a reproduction attempt demonstrated effects that were inconsistent with the original study (56%, 95% CI 42-68%), among which a large number were reported to be efficacious in the original study and to lack efficacy in the reproduction attempt (34%, 95% CI 19-52%). Two practices reported to be efficacious in the original study were found to be harmful in the reproduction attempt. A minority of critical care practices with research published in high-profile journals were evaluated for reproducibility; less than half had reproducible effects.

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.

Comparison of the analgesic efficacy of oral ketorolac versus intramuscular tramadol after third molar surgery: A parallel, double-blind, randomized, placebo-controlled clinical trial

PubMed Central

Isiordia-Espinoza, Mario-Alberto; Martinez-Rider, Ricardo; Perez-Urizar, Jose

2016-01-01

Background Preemptive analgesia is considered an alternative for treating the postsurgical pain of third molar removal. The aim of this study was to evaluate the preemptive analgesic efficacy of oral ketorolac versus intramuscular tramadol after a mandibular third molar surgery. Material and Methods A parallel, double-blind, randomized, placebo-controlled clinical trial was carried out. Thirty patients were randomized into two treatment groups using a series of random numbers: Group A, oral ketorolac 10 mg plus intramuscular placebo (1 mL saline solution); or Group B, oral placebo (similar tablet to oral ketorolac) plus intramuscular tramadol 50 mg diluted in 1 mL saline solution. These treatments were given 30 min before the surgery. We evaluated the time of first analgesic rescue medication, pain intensity, total analgesic consumption and adverse effects. Results Patients taking oral ketorolac had longer time of analgesic covering and less postoperative pain when compared with patients receiving intramuscular tramadol. Conclusions According to the VAS and AUC results, this study suggests that 10 mg of oral ketorolac had superior analgesic effect than 50 mg of tramadol when administered before a mandibular third molar surgery. Key words:Ketorolac, tramadol, third molar surgery, pain, preemptive analgesia. PMID:27475688

Immediate vs. delayed insertion of intrauterine contraception after second trimester abortion: study protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background We describe the rationale and protocol for a randomized controlled trial (RCT) to assess whether intrauterine contraception placed immediately after a second trimester abortion will result in fewer pregnancies than current recommended practice of intended placement at 4 weeks post-abortion. Decision analysis suggests the novel strategy could substantially reduce subsequent unintended pregnancies and abortions. This paper highlights considerations of design, implementation and evaluation of a trial expected to provide rigorous evidence for appropriate insertion timing and health economics of intrauterine contraception after second trimester abortion. Methods/Design Consenting women choosing to use intrauterine contraception after abortion for a pregnancy of 12 to 24 weeks will be randomized to insertion timing groups either immediately (experimental intervention) or four weeks (recommended care) post abortion. Primary outcome measure is pregnancy rate at one year. Secondary outcomes include: cumulative pregnancy rates over five year follow-up period, comprehensive health economic analyses comparing immediate and delayed insertion groups, and device retention rates, complication rates (infection, expulsion) and, contraceptive method satisfaction. Web-based Contraception Satisfaction Questionnaires, clinical records and British Columbia linked health databases will be used to assess primary and secondary outcomes. Enrolment at all clinics in the province performing second trimester abortions began in May 2010 and is expected to complete in late 2011. Data on one year outcomes will be available for analysis in 2014. Discussion The RCT design combined with access to clinical records at all provincial abortion clinics, and to information in provincial single-payer linked administrative health databases, birth registry and hospital records, offers a unique opportunity to evaluate such an approach by determining pregnancy rate at one through five years among enrolled women. We highlight considerations of design, implementation and evaluation of a trial expected to provide rigorous evidence for appropriate insertion timing and health economics of intrauterine contraception after second trimester abortion. Trial registration Current Controlled Trials ISRCTN19506752 PMID:21672213

Critical periods after stroke study: translating animal stroke recovery experiments into a clinical trial

PubMed Central

Dromerick, Alexander W.; Edwardson, Matthew A.; Edwards, Dorothy F.; Giannetti, Margot L.; Barth, Jessica; Brady, Kathaleen P.; Chan, Evan; Tan, Ming T.; Tamboli, Irfan; Chia, Ruth; Orquiza, Michael; Padilla, Robert M.; Cheema, Amrita K.; Mapstone, Mark E.; Fiandaca, Massimo S.; Federoff, Howard J.; Newport, Elissa L.

2015-01-01

Introduction: Seven hundred ninety-five thousand Americans will have a stroke this year, and half will have a chronic hemiparesis. Substantial animal literature suggests that the mammalian brain has much potential to recover from acute injury using mechanisms of neuroplasticity, and that these mechanisms can be accessed using training paradigms and neurotransmitter manipulation. However, most of these findings have not been tested or confirmed in the rehabilitation setting, in large part because of the challenges in translating a conceptually straightforward laboratory experiment into a meaningful and rigorous clinical trial in humans. Through presentation of methods for a Phase II trial, we discuss these issues and describe our approach. Methods: In rodents there is compelling evidence for timing effects in rehabilitation; motor training delivered at certain times after stroke may be more effective than the same training delivered earlier or later, suggesting that there is a critical or sensitive period for strongest rehabilitation training effects. If analogous critical/sensitive periods can be identified after human stroke, then existing clinical resources can be better utilized to promote recovery. The Critical Periods after Stroke Study (CPASS) is a phase II randomized, controlled trial designed to explore whether such a sensitive period exists. We will randomize 64 persons to receive an additional 20 h of upper extremity therapy either immediately upon rehab admission, 2–3 months after stroke onset, 6 months after onset, or to an observation-only control group. The primary outcome measure will be the Action Research Arm Test (ARAT) at 1 year. Blood will be drawn at up to 3 time points for later biomarker studies. Conclusion: CPASS is an example of the translation of rodent motor recovery experiments into the clinical setting; data obtained from this single site randomized controlled trial will be used to finalize the design of a Phase III trial. PMID:25972803

Measure Of Frequency Of Alveolar Osteitis Using Two Different Methods Of Osteotomy In Mandibular Third Molar Impactions: A Double-Blind Randomized Clinical Trial.

PubMed

Rashid, Hina; Hussain, Azmina; Sheikh, Abdul Hafeez; Azam, Kehkishan; Malik, Sofia; Amin, Muhammad

2018-01-01

Dento-alveolar surgical procedures involving third molar teeth are the most common surgical procedure in the field of surgery. The objective of this research was to analyse the impact of surgery on the incidence of alveolar osteitis after surgical removal of mandibular third molar and to compare two different bone cutting methods following impacted mandibular third molar surgery.. This double blinded randomized clinical trial was executed at the OPD of Department of Oral and Maxillofacial Surgery, Dow University of Health Sciences, Karachi. The study duration was four months. It was conducted on 60 patients needing unilateral mandibular third molar impaction removal. Patients were randomized to two groups (i.e., physio dispenser group and slow speed handpiece group) before surgery. The surgical procedure was performed under local anaesthesia by using standardized cross infection protocol. The frequency of alveolar osteitis was evaluated on thirdday postoperatively. Alveolar osteitis was diagnosed and confirmed by patient's history and clinical evaluation. Post-operative sequelae were observed and recorded objectively. Out of 60 patients', five patients experienced alveolar osteitis, and the incidence rate was 8.3%. A significant pvalue of 0.000 was calculated using binomial test for comparison of alveolar osteitis among both groups. Inter-examiner reliability was assessed by kappa and good (62%) agreement, which was found among the examiners, who diagnosed alveolar osteitis clinically. Post-operative sequelae were insignificant in slow speed hand piece group. It was observed that alveolar osteitis was reported in physio-dispenser group; similarly, post-operative complications were also more in this group as compared with slow speed-hand piece group. No surgical complications were observed in slow speed-hand piece group suggesting slow speed hand piece mode of osteotomy to be safer for third molar extraction as compared with physio-dispenser.

A Randomized-Controlled Trial Examining the Effects of Reflexology on Anxiety of Patients Undergoing Coronary Angiography

PubMed Central

Molavi Vardanjani, Mehdi; Masoudi Alavi, Negin; Razavi, Narges Sadat; Aghajani, Mohammad; Azizi-Fini, Esmail; Vaghefi, Seied Morteza

2013-01-01

Background: The anxiety reduction before coronary angiography has clinical advantages and is one of the objectives of nursing. Reflexology is a non-invasive method that has been used in several clinical situations. Applying reflexology might have effect on the reduction of anxiety before coronary angiography. Objectives: The aim of this randomized clinical trial was to investigate the effect of reflexology on anxiety among patients undergoing coronary angiography. Patients and Methods: This trial was conducted in Shahid Beheshti Hospital, in Kashan, Iran. One hundred male patients who were undergoing coronary angiography were randomly enrolled into intervention and placebo groups. The intervention protocol was included 30 minutes of general foot massage and the stimulation of three reflex points including solar plexus, pituitary gland, and heart. The placebo group only received the general foot massage. Spielbergers state trait anxiety inventory was used to assess the anxiety experienced by patients. Data was analyzed using Man-Witney, Wilcoxon and Chi-square tests. The stepwise multiple regressions used to analyze the variables that are involved in anxiety reduction. Results: The mean range of anxiety decreased from 53.24 to 45.24 in reflexology group which represented 8 score reduction (P = 0.0001). The reduction in anxiety was 5.9 score in placebo group which was also significant (P = 0.0001). The anxiety reduction was significantly higher in reflexology group (P = 0.014). The stepwise multiple regression analysis showed that doing reflexology can explain the 7.5% of anxiety reduction which made a significant model. Conclusions: Reflexology can decrease the anxiety level before coronary angiography. Therefore, reflexology before coronary angiography is recommended. PMID:25414869

Fetal head detection and measurement in ultrasound images by an iterative randomized Hough transform

NASA Astrophysics Data System (ADS)

Lu, Wei; Tan, Jinglu; Floyd, Randall C.

2004-05-01

This paper describes an automatic method for measuring the biparietal diameter (BPD) and head circumference (HC) in ultrasound fetal images. A total of 217 ultrasound images were segmented by using a K-Mean classifier, and the head skull was detected in 214 of the 217 cases by an iterative randomized Hough transform developed for detection of incomplete curves in images with strong noise without user intervention. The automatic measurements were compared with conventional manual measurements by sonographers and a trained panel. The inter-run variations and differences between the automatic and conventional measurements were small compared with published inter-observer variations. The results showed that the automated measurements were as reliable as the expert measurements and more consistent. This method has great potential in clinical applications.

Efficacy of chemomechanical caries removal in reducing cariogenic microbiota: a randomized clinical trial.

PubMed

Ammari, Michelle Mikhael; Moliterno, Luiz Flávio Martins; Hirata Júnior, Raphael; Séllos, Mariana Canano; Soviero, Vera Mendes; Coutinho Filho, Wagner Pereira

2014-01-01

The aim of this study was to compare the efficacy of chemochemical methods (Carisolv™ and Papacárie®) versus the manual method (excavators) in reducing the cariogenic microbiota in dentine caries of primary teeth. Forty-six healthy children (5 to 9 years old) having at least one primary tooth with a cavitated dentine carious lesion were included in the study. The teeth presented no clinical or radiographic signs of pulpal involvement. The sample of 74 teeth was randomly divided into three different groups: Papacárie® (n = 25), Carisolv™ (n = 27) and Manual (n = 22). Samples of carious and sound dentine were collected with sterile excavators before and after caries removal in the three groups. The dentine samples were transferred to glass tubes containing a 1mL thioglycollate medium used as a carrier and enriched for microbiological detection of mutans streptococci and Lactobacillus spp, after incubation for 6h at room temperature. The minimum detection value for colony forming units (CFU) was 3.3 x 102 CFU/ml, and the results were converted into scores from 0 to 4. A significant difference was observed in relation to the microbiological scores before and after caries removal for all methods (Wilcoxon test; p < 0.001). The use of chemomechanical methods for caries removal did not improve the reduction of cariogenic microorganisms in dentine caries lesions, in comparison with manual excavation.

RAPD- and ERIC-Based Typing of Clinical and Environmental Pseudomonas aeruginosa Isolates.

PubMed

Auda, Ibtesam Ghadban; Al-Kadmy, Israa M S; Kareem, Sawsan Mohammed; Lafta, Aliaa Khyuon; A'Affus, Mustafa Hussein Obeid; Khit, Ibrahim Abd Aloahd; Al Kheraif, Abdulaziz Abdullah; Divakar, Darshan Devang; Ramakrishnaiah, Ravikumar

2017-03-01

Pseudomonas aeruginosa is a major cause of nosocomial infection in children and adults, resulting in significant morbidity and mortality due to its ability to acquire drug resistance. The ability of P. aeruginosa in the environment to cause infection in individuals has been reported previously; henceforth, surveillance of the emergence and transmission of P. aeruginosa strains among patients is important for infection control in a clinical setup. Various gene-typing methods have been used for epidemiological typing of P. aeruginosa isolates for the purpose of surveillance. In this work, the suitability and comparability of two typing methods, enterobacterial repetitive intergenic consensus (ERIC)-PCR and random amplification of polymorphic DNA (RAPD)-PCR fingerprinting, were studied to characterize P. aeruginosa strains isolated from clinical and environmental sources. Forty-four clinical and environmental bacterial isolates of P. aeruginosa were collected between October 2015 and January 2016. DNA extraction, ERIC-PCR and RAPD-PCR, agarose gel electrophoresis, and phylogenetic analyses were carried using the unweighted pair-group method with mean. RAPD typing revealed less clonality among clinical isolates, whereas the ERIC method showed greater similarity in comparison with RAPD. Environmental isolates, however, showed greater similarity using RAPD compared with ERIC typing. With only a few exceptions, most clinical isolates were distinct from environmental isolates, irrespective of the typing method. In conclusion, both the RAPD and ERIC typing methods proved to be good tools in understanding clonal diversity. The results also suggest that there is no relationship between clinical and environmental isolates. The absence of clonality among the clinical isolates may indicate that most P. aeruginosa infection cases could be endemic and not epidemic and that endemic infections may be due to nonclonal strains of P. aeruginosa.

Comparative efficacy of golimumab, infliximab, and adalimumab for moderately to severely active ulcerative colitis: a network meta-analysis accounting for differences in trial designs.

PubMed

Thorlund, Kristian; Druyts, Eric; Toor, Kabirraaj; Mills, Edward J

2015-05-01

To conduct a network meta-analysis (NMA) to establish the comparative efficacy of infliximab, adalimumab and golimumab for the treatment of moderately to severely active ulcerative colitis (UC). A systematic literature search identified five randomized controlled trials for inclusion in the NMA. One trial assessed golimumab, two assessed infliximab and two assessed adalimumab. Outcomes included clinical response, clinical remission, mucosal healing, sustained clinical response and sustained clinical remission. Innovative methods were used to allow inclusion of the golimumab trial data given the alternative design of this trial (i.e., two-stage re-randomization). After induction, no statistically significant differences were found between golimumab and adalimumab or between golimumab and infliximab. Infliximab was statistically superior to adalimumab after induction for all outcomes and treatment ranking suggested infliximab as the superior treatment for induction. Golimumab and infliximab were associated with similar efficacy for achieving maintained clinical remission and sustained clinical remission, whereas adalimumab was not significantly better than placebo for sustained clinical remission. Golimumab and infliximab were also associated with similar efficacy for achieving maintained clinical response, sustained clinical response and mucosal healing. Finally, golimumab 50 and 100 mg was statistically superior to adalimumab for clinical response and sustained clinical response, and golimumab 100 mg was also statistically superior to adalimumab for mucosal healing. The results of our NMA suggest that infliximab was statistically superior to adalimumab after induction, and that golimumab was statistically superior to adalimumab for sustained outcomes. Golimumab and infliximab appeared comparable in efficacy.

Pilot Study Comparing Closed Versus Open Tracheal Suctioning in Postoperative Neonates and Infants With Complex Congenital Heart Disease.

PubMed

Tume, Lyvonne N; Baines, Paul B; Guerrero, Rafael; Hurley, Margaret A; Johnson, Robert; Kalantre, Atul; Ramaraj, Ram; Ritson, Paul C; Walsh, Laura; Arnold, Philip D

2017-07-01

To determine the hemodynamic effect of tracheal suction method in the first 36 hours after high-risk infant heart surgery on the PICU and to compare open and closed suctioning techniques. Pilot randomized crossover study. Single PICU in United Kingdom. Infants undergoing surgical palliation with Norwood Sano, modified Blalock-Taussig shunt, or pulmonary artery banding in the first 36 hours postoperatively. Infants were randomized to receive open or closed (in-line) tracheal suctioning either for their first or second study tracheal suction in the first 36 hours postoperatively. Twenty-four infants were enrolled over 18 months, 11 after modified Blalock-Taussig shunt, seven after Norwood Sano, and six after pulmonary artery banding. Thirteen patients received the open suction method first followed by the closed suction method second, and 11 patients received the closed suction method first followed by the open suction method second in the first 36 hours after their surgery. There were statistically significant larger changes in heart rate (p = 0.002), systolic blood pressure (p = 0.022), diastolic blood pressure (p = 0.009), mean blood pressure (p = 0.007), and arterial saturation (p = 0.040) using the open suction method, compared with closed suctioning, although none were clinically significant (defined as requiring any intervention). There were no clinically significant differences between closed and open tracheal suction methods; however, there were statistically significant greater changes in some hemodynamic variables with open tracheal suctioning, suggesting that closed technique may be safer in children with more precarious physiology.

Timing and Completeness of Trial Results Posted at ClinicalTrials.gov and Published in Journals

PubMed Central

Riveros, Carolina; Dechartres, Agnes; Perrodeau, Elodie; Haneef, Romana; Boutron, Isabelle; Ravaud, Philippe

2013-01-01

Background The US Food and Drug Administration Amendments Act requires results from clinical trials of Food and Drug Administration–approved drugs to be posted at ClinicalTrials.gov within 1 y after trial completion. We compared the timing and completeness of results of drug trials posted at ClinicalTrials.gov and published in journals. Methods and Findings We searched ClinicalTrials.gov on March 27, 2012, for randomized controlled trials of drugs with posted results. For a random sample of these trials, we searched PubMed for corresponding publications. Data were extracted independently from ClinicalTrials.gov and from the published articles for trials with results both posted and published. We assessed the time to first public posting or publishing of results and compared the completeness of results posted at ClinicalTrials.gov versus published in journal articles. Completeness was defined as the reporting of all key elements, according to three experts, for the flow of participants, efficacy results, adverse events, and serious adverse events (e.g., for adverse events, reporting of the number of adverse events per arm, without restriction to statistically significant differences between arms for all randomized patients or for those who received at least one treatment dose). From the 600 trials with results posted at ClinicalTrials.gov, we randomly sampled 50% (n = 297) had no corresponding published article. For trials with both posted and published results (n = 202), the median time between primary completion date and first results publicly posted was 19 mo (first quartile = 14, third quartile = 30 mo), and the median time between primary completion date and journal publication was 21 mo (first quartile = 14, third quartile = 28 mo). Reporting was significantly more complete at ClinicalTrials.gov than in the published article for the flow of participants (64% versus 48% of trials, p<0.001), efficacy results (79% versus 69%, p = 0.02), adverse events (73% versus 45%, p<0.001), and serious adverse events (99% versus 63%, p<0.001). The main study limitation was that we considered only the publication describing the results for the primary outcomes. Conclusions Our results highlight the need to search ClinicalTrials.gov for both unpublished and published trials. Trial results, especially serious adverse events, are more completely reported at ClinicalTrials.gov than in the published article. Please see later in the article for the Editors' Summary PMID:24311990

A comparison of methods for estimating the weight of preterm infants.

PubMed

Elser, A S; Vessey, J A

1995-09-01

Four methods of predicting a preterm infant's weight (upper mid-arm circumference, gestational age, tape measure nomogram, and guessing) were investigated to see which was the most accurate. The weights of 37 preterm neonates were initially guessed by an experienced clinician, then estimated by the other three approaches applied in a random order, and then confirmed through actual weighing. The correlations between the four estimated weights and the actual weights were .96, .84, .97, and .98, respectively. The tape measure nomogram method was the best overall approach for clinical use.

ORTHODONTIC RETENTION. Studies of retention capacity, cost-effectiveness and long-term stability.

PubMed

Tynelius, Gudrun Edman

2014-01-01

Retention strategies, cost-effectiveness and long-term stability of treatment outcome are essential aspects of orthodontic treatment planning. The overall aim of this thesis was to compare and evaluate three different retention strategies, with special reference to short- and long-term clinical stability and cost-effectiveness. The approach was evidence-based, hence randomized controlled methodology was used in order to generate high levels of evidence. This thesis is based on four studies: Papers I and II are based on randomized controlled trials, evaluating the stability of treatment outcome after one and two years of retention, using three different retention strategies: a maxillary vacuum-formed retainer combined with a mandibular canine-to-canine retainer; a maxillary vacuum-formed retainer combined with stripping of the mandibular anterior teeth and a prefabricated positioner. Paper III presents a cost-minimization analysis of two years of retention treatment. Paper IV is based on a randomized controlled trial documenting the results five years post-retention. The following conclusions were drawn: Papers I and II. From a clinical perspective, asssessment after one year of retention disclosed that the three retention methods were successful in retaining the orthodontic treatment results. After two years of retention, all three retention methods were equally effective in controlling relapse at a clinically acceptable level. Most of the relapse occurred during the first year of retention; only minor or negligible changes were found during the second year. The subjects were grouped according to the level of compliance (excellent or good). After two years of retention there was a negative correlation between growth in body height and relapse of mandibular LII in the group of subjects with excellent compliance. The group with good compliance showed a positive correlation (Paper II, Figure 3). After two years of retention, growth in body height, initial crowding and gender had no significant influence on mandibular LII (Paper II, Figure 4 and Table 4). Paper III. The cost minimization analysis disclosed that although the three retention methods achieved clinically similar results, the associated societal costs differed. After two years of retention, the vacuum-formed retainer (VFR) in combination with a canine-to-canine retainer (CTC) was the least cost-effective retention appliance. Paper IV. After five years or more out of retention, the three retention methods had achieved equally favourable clinical results. Key conclusion and clinical implications. This study compared the short- and long-term outcomes of orthodontic retention by three different methods: a maxillary vacuum-formed retainer combined with a mandibular canine-to-canine retainer; a maxillary vacuum-formed retainer combined with stripping of the mandibular anterior teeth and a prefabricated positioner. All methods gave equally positive clinical results in both the short-term, i.e. after one and two years of retention, and in the long-term, five years or more post-retention. After two years of retention, the level of compliance affected the retention treatment result. However, no such effect was shown for body height, the severity of initial crowding or gender. Today, there is increasing emphasis on the importance of economic aspects of healthcare. Of the three methods evaluated in this study, the least cost-effective, after two years of retention, was a vacuum-formed retainer combined with a bonded canine-to-canine retainer. The clinical implication of this finding is that in patients meeting the inclusion criteria, interproximal stripping of the mandibular anterior teeth, or the use of a prefabricated positioner, are highly appropriate alternatives to a mandibular bonded canine-to-canine retainer. The overall conclusions are that there are a number of effective retention methods available and the clinician is not limited to routine use of a bonded mandibular canine-to-canine retainer. The most appropriate retention method should be selected on an individual, case to case basis, taking into account such variables as orthodontic diagnosis, the expected level of patient compliance, patient preferences and financial considerations.

A descriptive study of culture media in Brazilian assisted reproduction clinics

PubMed Central

Bartmann, Ana; do Amaral, Amanda Turato Barbosa; Gonçalves, Letícia

2016-01-01

Objective The present study aimed to draw a profile of the most commonly used media and protocol characteristics from assisted reproduction technology (ART) facilities in Brazil. Methods To obtain an overview of ART methods and culture media, a questionnaire was given to embryologists from ART clinics in Brazil. Further research in scientific papers and journals was carried out for describing the processes around Brazil, USA and Europe. Results From the questionnaire, we found that the embryo medium mostly used is CSCMTM from Irvine Scientific, represented 37.04% in Brazilian ART clinics; interestingly, 70.37% of clinics exchange the embryo media bath; however, 70.37% do not change the media type. Transfers in Brazilian clinics were variable, but day 3 transfer was a procedure seen in 37.04%. The remaining embryos are habitually maintained in prolonged cultivation in 51.85% of the clinics interviewed. Conclusion Although there are numerous studies trying to better understand embryo culture media influences, there is a lack of evidence for choosing one as the most appropriate. In short, it is a random decision for such an essential stage of In Vitro Fertilization. PMID:27584601

Multilevel mixed effects parametric survival models using adaptive Gauss-Hermite quadrature with application to recurrent events and individual participant data meta-analysis.

PubMed

Crowther, Michael J; Look, Maxime P; Riley, Richard D

2014-09-28

Multilevel mixed effects survival models are used in the analysis of clustered survival data, such as repeated events, multicenter clinical trials, and individual participant data (IPD) meta-analyses, to investigate heterogeneity in baseline risk and covariate effects. In this paper, we extend parametric frailty models including the exponential, Weibull and Gompertz proportional hazards (PH) models and the log logistic, log normal, and generalized gamma accelerated failure time models to allow any number of normally distributed random effects. Furthermore, we extend the flexible parametric survival model of Royston and Parmar, modeled on the log-cumulative hazard scale using restricted cubic splines, to include random effects while also allowing for non-PH (time-dependent effects). Maximum likelihood is used to estimate the models utilizing adaptive or nonadaptive Gauss-Hermite quadrature. The methods are evaluated through simulation studies representing clinically plausible scenarios of a multicenter trial and IPD meta-analysis, showing good performance of the estimation method. The flexible parametric mixed effects model is illustrated using a dataset of patients with kidney disease and repeated times to infection and an IPD meta-analysis of prognostic factor studies in patients with breast cancer. User-friendly Stata software is provided to implement the methods. Copyright © 2014 John Wiley & Sons, Ltd.

Automatic co-segmentation of lung tumor based on random forest in PET-CT images

NASA Astrophysics Data System (ADS)

Jiang, Xueqing; Xiang, Dehui; Zhang, Bin; Zhu, Weifang; Shi, Fei; Chen, Xinjian

2016-03-01

In this paper, a fully automatic method is proposed to segment the lung tumor in clinical 3D PET-CT images. The proposed method effectively combines PET and CT information to make full use of the high contrast of PET images and superior spatial resolution of CT images. Our approach consists of three main parts: (1) initial segmentation, in which spines are removed in CT images and initial connected regions achieved by thresholding based segmentation in PET images; (2) coarse segmentation, in which monotonic downhill function is applied to rule out structures which have similar standardized uptake values (SUV) to the lung tumor but do not satisfy a monotonic property in PET images; (3) fine segmentation, random forests method is applied to accurately segment the lung tumor by extracting effective features from PET and CT images simultaneously. We validated our algorithm on a dataset which consists of 24 3D PET-CT images from different patients with non-small cell lung cancer (NSCLC). The average TPVF, FPVF and accuracy rate (ACC) were 83.65%, 0.05% and 99.93%, respectively. The correlation analysis shows our segmented lung tumor volumes has strong correlation ( average 0.985) with the ground truth 1 and ground truth 2 labeled by a clinical expert.

A Randomized Clinical Trial of Acceptance and Commitment Therapy versus Progressive Relaxation Training for Obsessive-Compulsive Disorder

ERIC Educational Resources Information Center

Twohig, Michael P.; Hayes, Steven C.; Plumb, Jennifer C.; Pruitt, Larry D.; Collins, Angela B.; Hazlett-Stevens, Holly; Woidneck, Michelle R.

2010-01-01

Objective: Effective treatments for obsessive-compulsive disorder (OCD) exist, but additional treatment options are needed. The effectiveness of 8 sessions of acceptance and commitment therapy (ACT) for adult OCD was compared with progressive relaxation training (PRT). Method: Seventy-nine adults (61% female) diagnosed with OCD (mean age = 37…

A Randomized, Placebo-Controlled Study of Once-Daily Atomoxetine in the School Setting in Children with ADHD

ERIC Educational Resources Information Center

Weiss, Margaret; Tannock, Rosemary; Kratochvil, Christopher; Dunn, David; Velez-Borras, Jesus; Thomason, Christine; Tamura, Roy; Kelsey, Douglas; Stevens, Linda; Allen, Albert J.

2005-01-01

Objective: Five studies have demonstrated the effectiveness of atomoxetine compared with placebo in reducing symptoms of attention-deficit/hyperactivity disorder (ADHD) based on parent reports. The primary objective of this clinical trial was to assess the efficacy of once-daily atomoxetine compared with placebo using teacher reports. Method: One…

Positive Psychology Intervention to Alleviate Child Depression and Increase Life Satisfaction: A Randomized Clinical Trial

ERIC Educational Resources Information Center

Kwok, Sylvia Y. C. L.; Gu, Minmin; Kit, Katrina Tong Kai

2016-01-01

Purpose: The study aims to examine the effectiveness of a positive psychology group-based intervention program, incorporating elements of hope and gratitude, in decreasing depression and increasing life satisfaction among primary school students in Hong Kong. Method: A total of 68 children, with the Depression score of Chinese Hospital Anxiety and…

Medication and Parent Training in Children with Pervasive Developmental Disorders and Serious Behavior Problems: Results from a Randomized Clinical Trial

ERIC Educational Resources Information Center

Aman, Michael G.; McDougle, Christopher J.; Scahill, Lawrence; Handen, Benjamin; Arnold, L. Eugene; Johnson, Cynthia; Stigler, Kimberly A.; Bearss, Karen; Butter, Eric; Swiezy, Naomi B.; Sukhodolsky, Denis D.; Ramadan, Yaser; Pozdol, Stacie L.; Nikolov, Roumen; Lecavalier, Luc; Kohn, Arlene E.; Koenig, Kathleen; Hollway, Jill A.; Korzekwa, Patricia; Gavaletz, Allison; Mulick, James A.; Hall, Kristy L.; Dziura, James; Ritz, Louise; Trollinger, Stacie; Yu, Sunkyung; Vitiello, Benedetto; Wagner, Ann

2009-01-01

Objective: Many children with pervasive developmental disorders (PDDs) have serious, functionally impairing behavioral problems. We tested whether combined treatment (COMB) with risperidone and parent training (PT) in behavior management is superior to medication alone (MED) in improving severe behavioral problems in children with PDDs. Method:…

Atomoxetine for Hyperactivity in Autism Spectrum Disorders: Placebo-Controlled Crossover Pilot Trial

ERIC Educational Resources Information Center

Arnold, L. Eugene; Aman, Michael G.; Cook, Amelia M.; Witwer, Andrea N.; Hall, Kristy L.; Thompson, Susan; Ramadan, Yaser

2006-01-01

Objective: To explore placebo-controlled efficacy and safety of atomoxetine (ATX) for attention-deficit/hyperactivity disorder (ADHD) symptoms in children with autism spectrum disorders (ASD). Method: Children ages 5 to 15 with ASD and prominent ADHD symptoms were randomly assigned to order in a crossover of clinically titrated ATX and placebo, 6…

Mediators of the Association of Major Depressive Syndrome and Anxiety Syndrome with Postpartum Smoking Relapse

ERIC Educational Resources Information Center

Correa-Fernandez, Virmarie; Ji, Lingyun; Castro, Yessenia; Heppner, Whitney L.; Vidrine, Jennifer Irvin; Costello, Tracy J.; Mullen, Patricia Dolan; Cofta-Woerpel, Ludmila; Velasquez, Mary M.; Greisinger, Anthony; Cinciripini, Paul M.; Wetter, David W.

2012-01-01

Objective: Based on conceptual models of addiction and affect regulation, this study examined the mechanisms linking current major depressive syndrome (MDS) and anxiety syndrome (AS) to postpartum smoking relapse. Method: Data were collected in a randomized clinical trial from 251 women who quit smoking during pregnancy. Simple and multiple…

Cost-Effectiveness of Case Management in Substance Abuse Treatment

ERIC Educational Resources Information Center

Saleh, Shadi S.; Vaughn, Thomas; Levey, Samuel; Fuortes, Laurence; Uden-Holmen, Tanya; Hall, James A.

2006-01-01

Objective: The purpose of this study, which is part of a larger clinical trial, was to examine the cost-effectiveness of case management for individuals treated for substance abuse in a residential setting. Method: Clients who agreed to participate were randomly assigned to one of four study groups. Two groups received face-to-face case management…

Comprehensive assessment of long-term effects of reducing intake of energy phase 2 (CALERIE Phase 2) screening and recruitment: Methods and results

USDA-ARS?s Scientific Manuscript database

The Comprehensive Assessment of the Long-term Effects of Reducing Intake of Energy Phase 2 (CALERIE) study is a systematic investigation of sustained 25% calorie restriction (CR) in non-obese humans. CALERIE is a multicenter (3 clinical sites, one coordinating center), parallel group, randomized con...

The comparative effects of 0.12% chlorhexidine and herbal oral rinse on dental plaque-induced gingivitis: A randomized clinical trial

PubMed Central

Bhate, Devaki; Jain, Sanjay; Kale, Rahul; Muglikar, Sangeeta

2015-01-01

Background: Chlorhexidine (CHX) is considered as a gold standard of antimicrobial rinses. Various herbal oral rinses are available in the market. However, little is known of its effectiveness. Aim: The aim of this study was to evaluate the clinical changes after the usage of herbal oral rinse and 0.12% CHX. Materials and Methods: In a randomized clinical trial, 76 patients with dental plaque-induced gingivitis were assigned to Group I (Herbal Oral Rinse - Hiora®) and 76 patients with dental plaque-induced gingivitis to Group II (0.12% Chlorhexidine-Peridex®). Gingival index and Plaque index scores were recorded at baseline and 21 days after scaling. Results: Intragroup comparison in both groups showed that plaque index and gingival index scores were statistically significant after 21 days as compared to baseline. Intergroup comparison showed that plaque index scores and gingival index scores were statistically significant in Group II as compared to Group I. Conclusion: When herbal oral rinse was compared to 0.12% CHX, 0.12% CHX mouth rinse effectively reduced the clinical symptoms of plaque-induced gingivitis. PMID:26392686

Relapse prevention after index electroconvulsive therapy in treatment-resistant depression

PubMed Central

Youssef, Nagy A.; McCall, W. Vaughn

2015-01-01

Background One-third of patients who suffer from depression are resistant to conventional treatments. An acute course of electroconvulsive therapy (ECT) can lead to remission of depressive symptoms in a substantial portion of the treatment-resistant patients. However, prevention of relapse with depressive symptoms after the index course of ECT can be challenging. We review pertinent studies on the topic and analyze the best strategies to avoid relapse and recurrence of depressive symptoms. Methods We performed a systematic literature review of PubMed through April 2014 for clinical trials published in English to determine if continuation ECT, continuation medication, continuation psychotherapy, or combinations of these are the best strategy to avoid relapse and recurrence of depressive symptoms after an acute course of ECT. Clinical trials comparing ≥2 of the above strategies were included in the review. Results Although there are few rigorous randomized clinical trials in this area, most studies suggest that combined continuation ECT (C-ECT) and continuation pharmacotherapy are the most effective strategy in relapse prevention. Conclusions C-ECT and continuation pharmacotherapy may be more effective than either alone for preventing relapse. However, more definitive randomized clinical trials are needed. PMID:25401716

Comparison of high glucose concentration blood and crystalloid cardioplegia in paediatric cardiac surgery: a randomized clinical trial

PubMed Central

Mimic, Branko; Ilic, Slobodan; Vulicevic, Irena; Milovanovic, Vladimir; Tomic, Danijela; Mimic, Ana; Stankovic, Sanja; Zecevic, Tatjana; Davies, Ben; Djordjevic, Miroslav

2016-01-01

OBJECTIVES This study investigates the effects of high glucose content on patients undergoing cold crystalloid versus cold blood cardioplegia in terms of early clinical results, functional myocardial recovery and ischaemia–reperfusion injury in patients undergoing repair of acyanotic cardiac lesions. METHODS Patients were randomly assigned to receive either crystalloid (n = 31) or blood cardioplegia (n = 31). Early clinical results were assessed. Changes in left ventricular fractional shortening, arterial blood lactate levels, central venous saturation, cardiac Troponin I release and blood glucose concentration were measured during the first 24 h after ischaemia. RESULTS There was no significant difference in clinical outcomes and postoperative complication rates between groups. The postoperative changes in left ventricular function, lactate levels, central venous saturation and Troponin I were not significantly different between groups. The use of crystalloid cardioplegia was associated with significant increases in serum glucose compared with blood cardioplegia. CONCLUSIONS A high glucose content blood cardioplegia does not show any advantage compared with crystalloid cardioplegia in terms of clinical outcomes, functional recovery and the degree of ischaemic injury in infants and children undergoing repair of acyanotic heart lesions. High glucose concentration of the cardioplegic solution might potentiate ischaemia–reperfusion injury and diminish the beneficial effects of blood cardioplegia. PMID:26831677

Efficiency and effectiveness of the use of an acenocoumarol pharmacogenetic dosing algorithm versus usual care in patients with venous thromboembolic disease initiating oral anticoagulation: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Hemorrhagic events are frequent in patients on treatment with antivitamin-K oral anticoagulants due to their narrow therapeutic margin. Studies performed with acenocoumarol have shown the relationship between demographic, clinical and genotypic variants and the response to these drugs. Once the influence of these genetic and clinical factors on the dose of acenocoumarol needed to maintain a stable international normalized ratio (INR) has been demonstrated, new strategies need to be developed to predict the appropriate doses of this drug. Several pharmacogenetic algorithms have been developed for warfarin, but only three have been developed for acenocoumarol. After the development of a pharmacogenetic algorithm, the obvious next step is to demonstrate its effectiveness and utility by means of a randomized controlled trial. The aim of this study is to evaluate the effectiveness and efficiency of an acenocoumarol dosing algorithm developed by our group which includes demographic, clinical and pharmacogenetic variables (VKORC1, CYP2C9, CYP4F2 and ApoE) in patients with venous thromboembolism (VTE). Methods and design This is a multicenter, single blind, randomized controlled clinical trial. The protocol has been approved by La Paz University Hospital Research Ethics Committee and by the Spanish Drug Agency. Two hundred and forty patients with VTE in which oral anticoagulant therapy is indicated will be included. Randomization (case/control 1:1) will be stratified by center. Acenocoumarol dose in the control group will be scheduled and adjusted following common clinical practice; in the experimental arm dosing will be following an individualized algorithm developed and validated by our group. Patients will be followed for three months. The main endpoints are: 1) Percentage of patients with INR within the therapeutic range on day seven after initiation of oral anticoagulant therapy; 2) Time from the start of oral anticoagulant treatment to achievement of a stable INR within the therapeutic range; 3) Number of INR determinations within the therapeutic range in the first six weeks of treatment. Discussion To date, there are no clinical trials comparing pharmacogenetic acenocoumarol dosing algorithm versus routine clinical practice in VTE. Implementation of this pharmacogenetic algorithm in the clinical practice routine could reduce side effects and improve patient safety. Trial registration Eudra CT. Identifier: 2009-016643-18. PMID:23237631

A cross-sectional analysis of HIV and hepatitis C clinical trials 2007 to 2010: the relationship between industry sponsorship and randomized study design

PubMed Central

2014-01-01

Background The proportion of clinical research sponsored by industry will likely continue to expand as federal funds for academic research decreases, particularly in the fields of HIV/AIDS and hepatitis C (HCV). While HIV and HCV continue to burden the US population, insufficient data exists as to how industry sponsorship affects clinical trials involving these infectious diseases. Debate exists about whether pharmaceutical companies undertake more market-driven research practices to promote therapeutics, or instead conduct more rigorous trials than their non-industry counterparts because of increased resources and scrutiny. The ClinicalTrials.gov registry, which allows investigators to fulfill a federal mandate for public trial registration, provides an opportunity for critical evaluation of study designs for industry-sponsored trials, independent of publication status. As part of a large public policy effort, the Clinical Trials Transformation Initiative (CTTI) recently transformed the ClinicalTrials.gov registry into a searchable dataset to facilitate research on clinical trials themselves. Methods We conducted a cross-sectional analysis of 477 HIV and HCV drug treatment trials, registered with ClinicalTrials.gov from 1 October 2007 to 27 September 2010, to study the relationship of study sponsorship with randomized study design. The likelihood of using randomization given industry (versus non-industry) sponsorship was reported with prevalence ratios (PR). PRs were estimated using crude and stratified tabular analysis and Poisson regression adjusting for presence of a data monitoring committee, enrollment size, study phase, number of study sites, inclusion of foreign study sites, exclusion of persons older than age 65, and disease condition. Results The crude PR was 1.17 (95% CI 0.94, 1.45). Adjusted Poisson models produced a PR of 1.13 (95% CI 0.82, 1.56). There was a trend toward mild effect measure modification by study phase, but this was not statistically significant. In stratified tabular analysis the adjusted PR was 1.14 (95% CI 0.78, 1.68) among phase 2/3 trials and 1.06 (95% CI 0.50, 2.22) among phase 4 trials. Conclusions No significant relationship was found between industry sponsorship and use of randomization in trial design in this cross-sectional study. Prospective studies evaluating other aspects of trial design may shed further light on the relationship between industry sponsorship and appropriate trial methodology. PMID:24450313

Clinical Hypnosis in the Treatment of Post-Menopausal Hot Flashes: A Randomized Controlled Trial

PubMed Central

Elkins, Gary R.; Fisher, William I.; Johnson, Aimee K.; Carpenter, Janet S.; Keith, Timothy Z.

2012-01-01

Objective The use of estrogen and progesterone to manage vasomotor symptoms (i.e., hot flashes, night sweats) has declined due to concerns over their risks and there is an increased interest in alternate, effective, and low-risk treatments. This study reports the results of a randomized, controlled trial of clinical hypnosis in treating vasomotor symptoms among post-menopausal women. Methods Randomized, single-blind, controlled, clinical trial involving 187 post-menopausal women reporting a minimum of seven hot flashes per day, or at least 50 hot flashes a week at baseline between December 2008 and April 2012. Eligible participants received five weekly sessions of either clinical hypnosis or structured-attention control. Primary outcomes were hot flash frequency (subjectively and physiologically recorded) and hot flash score assessed by daily diaries at weeks 2–6, and 12. Secondary outcomes included measures of hot flash related daily interference, sleep quality and treatment satisfaction. Results In a modified intent-to-treat analysis that included all randomized participants that provided data, reported subjective hot flash frequency from baseline to week 12 showed a mean reduction of 55.82 hot flashes for the clinical hypnosis intervention (74.16%), versus a 12.89 hot flash reduction (17.13%) for the control (p<.001, 95% CI, 36.15–49.67). Mean reduction in hot flash score was 18.83 (80.32%) for the clinical hypnosis intervention as compared to 3.53 (15.38%) for the control (p<.001, 95% CI, 12.60–17.54). At 12 week follow-up, the mean reduction in physiologically monitored hot flashes was 5.92 (56.86%) for clinical hypnosis and .88 (9.94%) for the control (p<.001, 95% CI, 2.00–5.46). Secondary outcomes were significantly improved compared to control at 12 week follow-up in hot flash related interference (p<.001, 95% CI, 2.74–4.02), sleep quality (p<.001, 95% CI, 3.65–5.84), and treatment satisfaction (p<.001, 95% CI, 7.79–8.59). Conclusion Compared to a structured attention control, clinical hypnosis resulted in significant reductions in self-reported and physiologically measured hot flashes as well as hot flash scores in post-menopausal women. PMID:23435026

Double-Blind Randomized Clinical Trial: Gluten versus Placebo Rechallenge in Patients with Lymphocytic Enteritis and Suspected Celiac Disease

PubMed Central

Carrasco, Anna; Ibarra, Montserrat; Temiño, Rocío; Salas, Antonio; Esteve, Maria

2016-01-01

Background The role of gluten as a trigger of symptoms in non-coeliac gluten sensitivity has been questioned. Aim To demonstrate that gluten is the trigger of symptoms in a subgroup of patients fulfilling the diagnostic criteria for non-coeliac gluten sensitivity (NCGS), which presented with lymphocytic enteritis, positive celiac genetics and negative celiac serology. Methods Double-blind randomized clinical trial of gluten vs placebo rechallenge. Inclusion criteria: >18 years of age, HLA-DQ2/8+, negative coeliac serology and gluten-dependent lymphocytic enteritis, and GI symptoms, with clinical and histological remission at inclusion. Eighteen patients were randomised: 11 gluten (20 g/day) and 7 placebo. Clinical symptoms, quality of life (GIQLI), and presence of gamma/delta+ cells and transglutaminase deposits were evaluated. Results 91% of patients had clinical relapse during gluten challenge versus 28.5% after placebo (p = 0.01). Clinical scores and GIQLI worsened after gluten but not after placebo (p<0.01). The presence of coeliac tissue markers at baseline biopsy on a gluten-free diet allowed classifying 9 out of the 18 (50%) patients as having probable ‘coeliac lite’ disease. Conclusion This proof-of-concept study indicates that gluten is the trigger of symptoms in a subgroup of patients fulfilling the diagnostic criteria for NCGS. They were characterized by positive celiac genetics, lymphocytic enteritis, and clinical and histological remission after a gluten-free diet. Trial Registration ClinicalTrials.gov NCT02472704 PMID:27392045

The clinical content of NHS trust board meetings: an initial exploration.

PubMed

Watkins, Mary; Jones, Ray; Lindsey, Laura; Sheaff, Rod

2008-09-01

To differentiate between English NHS trust board meetings according to the percentage of clinical content and to explore which characteristics of board meetings might explain this. Definition of scoring system for clinical content. Scoring of minutes for a random sample of 60 trusts. Qualitative analysis of a sub-sample, generated hypotheses about factors leading to higher percentage of clinical items was undertaken; testing of hypotheses in a longitudinal sample of minutes from 24 trusts over 1 year. Clinical content varied from 2% to 30%. Boards with a more clinical focus tended to link other issues including finance to clinical issues; have non-executive directors able to question board executives openly; make less use of acronyms in minutes; had more liaison with social services; and accepted questions from the public. Counting items in board minutes has prima facie validity as a means of defining how clinically focussed board meetings are, although more research is required to refine the method. The present method of analysing board minutes may provide one way of assessing board culture. Directors of nursing can help focus trust board meetings on clinical matters. Further research is required to determine whether greater clinical content in trust board meetings has impacts on clinical practice or organizational performance.

Hypnosis and Local Anesthesia for Dental Pain Relief-Alternative or Adjunct Therapy?-A Randomized, Clinical-Experimental Crossover Study.

PubMed

Wolf, Thomas Gerhard; Wolf, Dominik; Callaway, Angelika; Below, Dagna; d'Hoedt, Bernd; Willershausen, Brita; Daubländer, Monika

2016-01-01

This prospective randomized clinical crossover trial was designed to compare hypnosis and local anesthesia for experimental dental pain relief. Pain thresholds of the dental pulp were determined. A targeted standardized pain stimulus was applied and rated on the Visual Analogue Scale (0-10). The pain threshold was lower under hypnosis (58.3 ± 17.3, p < .001), maximal (80.0) under local anesthesia. The pain stimulus was scored higher under hypnosis (3.9 ± 3.8) than with local anesthesia (0.0, p < .001). Local anesthesia was superior to hypnosis and is a safe and effective method for pain relief in dentistry. Hypnosis seems to produce similar effects observed under sedation. It can be used in addition to local anesthesia and in individual cases as an alternative for pain control in dentistry.

[Stimulation of wound healing by tetrachlordecaoxide. Results of a randomized double-blind study].

PubMed

Hinz, J; Hautzinger, H; Helling, J; Schirren, G; Sell, G; Stahl, K W; Kühne, F W

1984-05-10

In 38 patients with chronic therapeutically resistant wounds, which, in 25 cases, had been existing for more than one year, Tetrachlorodecaoxide ( TCDO ) in a water solution containing glycerin was analyzed for its capacity to induce wound healing and compared in this respect to the standard in moist wound treatment, physiological sodium chloride. The results of the clinical trial demonstrate that the TCDO solution is significantly superior to physiological saline in local wound treatment regarding the degree of wound smear reduction, the formation of wound granulation tissue, the stimulation of epithelisation on the wound borders and the shrinking of the wound surface. The differences in therapeutic efficiency are so large that, in spite of the relatively small patient samples (21 + 17) it was possible to verify the superiority of a method for wound treatment in a randomized double blind clinical trial.