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Sample records for 02-98 randomized trial

  1. Challenges of cluster randomized trials.

    PubMed

    Campbell, Michael J

    2014-05-01

    Cluster randomized trials are trials that randomize clusters of people, rather than individuals. They are becoming increasingly common. A number of innovations have been developed recently, particularly in the calculation of the required size of a cluster trial, the handling of missing data, designs to minimize recruitment bias, the ethics of cluster randomized trials and the stepped wedge design. This article will highlight and illustrate these developments. It will also discuss issues with regards to the reporting of cluster randomized trials.

  2. Randomized phase II clinical trials.

    PubMed

    Jung, Sin-Ho; Sargent, Daniel J

    2014-01-01

    Traditionally, Phase II trials have been conducted as single-arm trials to compare the response probabilities between an experimental therapy and a historical control. Historical control data, however, often have a small sample size, are collected from a different patient population, or use a different response assessment method, so that a direct comparison between a historical control and an experimental therapy may be severely biased. Randomized Phase II trials entering patients prospectively to both experimental and control arms have been proposed to avoid any bias in such cases. The small sample sizes for typical Phase II clinical trials imply that the use of exact statistical methods for their design and analysis is appropriate. In this article, we propose two-stage randomized Phase II trials based on Fisher's exact test, which does not require specification of the response probability of the control arm for testing. Through numerical studies, we observe that the proposed method controls the type I error accurately and maintains a high power. If we specify the response probabilities of the two arms under the alternative hypothesis, we can identify good randomized Phase II trial designs by adopting the Simon's minimax and optimal design concepts that were developed for single-arm Phase II trials.

  3. Experimental studies: randomized clinical trials.

    PubMed

    Gjorgov, A N

    1998-01-01

    There are two major approaches to medical investigations: observational studies and experimental trials. The classical application of the experimental design to studies of human populations is the randomized clinical trial of the efficacy of a new drug or treatment. A further application of the experimental studies is to the testing of hypotheses about the etiology of a disease, already tested and corroborated from various forms of observational studies. Ethical considerations and requirements for consent of the experimental subjects are of primary concern in the clinical trials, and those concerns set the first and final limits for implementing a trial. General moral principles in research with human and animal beings, defined by the "Nuremberg Code," deal with strict criteria for approval, endorsement and evaluation of a clinical trial.

  4. Final Technical Report for Award DE-FG02-98ER41080

    SciTech Connect

    Chen, Alan

    2014-11-14

    The prime motivation of the project at McMaster University was to carry out the critical evaluation and compilation of Nuclear Structure and Decay data, and of nuclear astrophysics data with continued participation in the United States Nuclear Data Program (US-NDP). A large body of evaluated and compiled structure data were supplied for databases such as ENSDF, XUNDL, NSR, etc. residing on webpage of National Nuclear Data Center of the Brookhaven National Laboratory, Upton, New York, USA. Thermonuclear reaction rates of importance to stellar explosions, such as novae, x-ray bursts and supernovae, were evaluated as well. This effort was closely coupled to our ongoing experimental effort, which took advantage of radioactive ion beam and stable beam facilities worldwide to study these key reaction rates. This report contains brief descriptions of the various activities together with references to all the publications in peer-reviewed journals which were the result of work carried out with the award DE-FG02-98-ER41080, during 1998-2013.

  5. The Design of Cluster Randomized Crossover Trials

    ERIC Educational Resources Information Center

    Rietbergen, Charlotte; Moerbeek, Mirjam

    2011-01-01

    The inefficiency induced by between-cluster variation in cluster randomized (CR) trials can be reduced by implementing a crossover (CO) design. In a simple CO trial, each subject receives each treatment in random order. A powerful characteristic of this design is that each subject serves as its own control. In a CR CO trial, clusters of subjects…

  6. The Design of Cluster Randomized Crossover Trials

    ERIC Educational Resources Information Center

    Rietbergen, Charlotte; Moerbeek, Mirjam

    2011-01-01

    The inefficiency induced by between-cluster variation in cluster randomized (CR) trials can be reduced by implementing a crossover (CO) design. In a simple CO trial, each subject receives each treatment in random order. A powerful characteristic of this design is that each subject serves as its own control. In a CR CO trial, clusters of subjects…

  7. A primer on randomized controlled trials.

    PubMed

    Likosky, Donald S

    2006-03-01

    Randomized Clinical Trials are held as the gold standard for quantifying the effect of an intervention across two or more groups. In such a trial an intervention is randomly allocated to one of two groups. The benefit of such a trial lies in its ability to establish nearly comparable groups of subjects in all manner except for the effect of the intervention. As such, the effect of a given intervention may be attributed solely to the intervention and not to any other extraneous factor. In the following editorial, we will discuss several issues that are important for understanding how to conduct and interpret randomized trials: choosing the study population, choosing the comparison group, choosing your outcome, study design, data analysis, and issues of inference. This editorial is intended to make the reader an educated consumer of such trial designs.

  8. Random allocation software for parallel group randomized trials.

    PubMed

    Saghaei, Mahmood

    2004-11-09

    Typically, randomization software should allow users to exert control over the different aspects of randomization including block design, provision of unique identifiers and control over the format and type of program output. While some of these characteristics have been addressed by available software, none of them have all of these capabilities integrated into one package. The main objective of the Random Allocation Software project was to enhance the user's control over different aspects of randomization in parallel group trials, including output type and format, structure and ordering of generated unique identifiers and enabling users to specify group names for more than two groups. The program has different settings for: simple and blocked randomizations; length, format and ordering of generated unique identifiers; type and format of program output; and saving sessions for future use. A formatted random list generated by this program can be used directly (without further formatting) by the coordinator of the research team to prepare and encode different drugs or instruments necessary for the parallel group trial. Random Allocation Software enables users to control different attributes of the random allocation sequence and produce qualified lists for parallel group trials.

  9. Random allocation software for parallel group randomized trials

    PubMed Central

    Saghaei, Mahmood

    2004-01-01

    Background Typically, randomization software should allow users to exert control over the different aspects of randomization including block design, provision of unique identifiers and control over the format and type of program output. While some of these characteristics have been addressed by available software, none of them have all of these capabilities integrated into one package. The main objective of the Random Allocation Software project was to enhance the user's control over different aspects of randomization in parallel group trials, including output type and format, structure and ordering of generated unique identifiers and enabling users to specify group names for more than two groups. Results The program has different settings for: simple and blocked randomizations; length, format and ordering of generated unique identifiers; type and format of program output; and saving sessions for future use. A formatted random list generated by this program can be used directly (without further formatting) by the coordinator of the research team to prepare and encode different drugs or instruments necessary for the parallel group trial. Conclusions Random Allocation Software enables users to control different attributes of the random allocation sequence and produce qualified lists for parallel group trials. PMID:15535880

  10. Antiplatelet agents and randomized trials.

    PubMed

    Diener, Hans-Christoph

    2007-01-01

    Patients who have transient ischemic attack (TIA) or ischemic stroke are at a high risk of having a first or recurrent stroke. The annual risk is between 5% and 15%; the risk is highest in the first 48 hours following a TIA and highest in the first 7 days following an ischemic stroke. Secondary prevention includes antithrombotic therapy, treatment of risk factors, and interventional treatment of carotid stenosis. Antithrombotic options can include antiplatelet drugs such as aspirin, aspirin plus extended-release dipyridamole (ER-DP), clopidogrel, or clopidogrel plus aspirin. Oral anticoagulation is used in patients with a cardiac source of embolism such as atrial fibrillation. Aspirin monotherapy offers a modest risk reduction for recurrent stroke and for the combined endpoint of nonfatal stroke, myocardial infarction (MI), and vascular death. The combination of ER-DP and aspirin was shown to be superior to aspirin monotherapy in several trials. Clopidogrel is superior to aspirin in high-risk patients suffering from stroke, MI, or peripheral arterial disease. The combination of clopidogrel plus aspirin is not superior to aspirin or clopidogrel monotherapy and carries a significantly higher bleeding risk. The combination might offer benefit in short-term secondary prevention after TIA or stroke. Another ongoing trial is currently investigating the possible benefit and side effects of aspirin plus ER-DP versus clopidogrel in secondary stroke prevention.

  11. Randomized Clinical Trials in Localized Anal Cancer.

    PubMed

    Smith, Clayton A; Kachnic, Lisa A

    2017-10-01

    Management of anal carcinoma began as abdominoperineal resection and has evolved to combined chemotherapy and radiation. Early randomized trials demonstrated superior clinical outcomes of combined modality therapy over radiotherapy alone. Subsequent trials investigated alterations in the standard backbone of radiotherapy concurrent with 5-fluorouracil and mitomycin C with intent to maintain clinical outcomes while reducing treatment-related morbidity. The addition of intensity-modulated radiotherapy to radiation planning and delivery has subsequently reduced acute toxicity and detrimental treatment breaks. Ongoing and future trials are aimed at reducing therapy in favorable patient populations to decrease morbidity while intensifying treatment in patients with negative prognostic factors. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Recruiting Participants for Randomized Controlled Trials

    ERIC Educational Resources Information Center

    Gallagher, H. Alix; Roschelle, Jeremy; Feng, Mingyu

    2014-01-01

    The objective of this study was to look across strategies used in a wide range of studies to build a framework for researchers to use in conceptualizing the recruitment process. This paper harvests lessons learned across 19 randomized controlled trials in K-12 school settings conducted by a leading research organization to identify strategies that…

  13. Reporting Randomized Controlled Trials in Education

    ERIC Educational Resources Information Center

    Mayo-Wilson, Evan; Grant, Sean; Montgomery, Paul

    2014-01-01

    Randomized controlled trials (RCTs) are increasingly used to evaluate programs and interventions in order to inform education policy and practice. High quality reports of these RCTs are needed for interested readers to understand the rigor of the study, the interventions tested, and the context in which the evaluation took place (Mayo-Wilson et…

  14. Neurosurgical Randomized Controlled Trials-Distance Travelled.

    PubMed

    Azad, Tej D; Veeravagu, Anand; Mittal, Vaishali; Esparza, Rogelio; Johnson, Eli; Ioannidis, John P A; Grant, Gerald A

    2017-06-21

    The evidence base for many neurosurgical procedures has been limited. We performed a comprehensive and systematic analysis of study design, quality of reporting, and trial results of neurosurgical randomized controlled trials (RCTs). To systematically assess the design and quality characteristics of neurosurgical RCTs. From January 1961 to June 2016, RCTs with >5 patients assessing any 1 neurosurgical procedure against another procedure, nonsurgical treatment, or no treatment were retrieved from MEDLINE, Scopus, and Cochrane Library. The median sample size in the 401 eligible RCTs was 73 patients with a mean patient age of 49.6. Only 111 trials (27.1%) described allocation concealment, 140 (34.6%) provided power calculations, and 117 (28.9%) were adequately powered. Significant efficacy or trend for efficacy was claimed in 226 reports (56.4%), no difference between the procedures was found in 166 trials (41.4%), and significant harm was reported in 9 trials (2.2%). Trials with a larger sample size were more likely to report randomization mode, specify allocation concealment, and power calculations (all P < .001). Government funding was associated with better specification of power calculations ( P = .008) and of allocation concealment ( P = .026), while industry funding was associated with reporting significant efficacy ( P = .02). Reporting of funding, specification of randomization mode and primary outcomes, and mention of power calculations improved significantly (all, P < .05) over time. Several aspects of the design and reporting of RCTs on neurosurgical procedures have improved over time. Better powered and accurately reported trials are needed in neurosurgery to deliver evidence-based care and achieve optimal outcomes.

  15. A pilot randomized controlled trial of deprescribing.

    PubMed

    Beer, Christopher; Loh, Poh-Kooi; Peng, Yan Gee; Potter, Kathleen; Millar, Alasdair

    2011-04-01

    Polypharmacy and adverse drug reactions are frequent and important among older people. Few clinical trials have evaluated systematic withdrawal of medications among older people. This small, open, study was conducted to determine the feasibility of a randomized controlled deprescribing trial. Ten volunteers living in the community (recruited by media advertising) and 25 volunteers living in residential aged-care facilities (RCFs) were randomized to intervention or control groups. The intervention was gradual withdrawal of one target medication. The primary outcome was the number of intervention participants in whom medication withdrawal could be achieved. Other outcomes measures were quality of life, medication adherence, sleep quality, and cognitive impairment. Participants were aged 80 ± 11 years and were taking 9 ± 2 medications. Fifteen participants commenced medication withdrawal and all ceased or reduced the dose of their target medication. Two subjects withdrew; one was referred for clinical review, and one participant declined further dose reductions. A randomized controlled trial of deprescribing was acceptable to participants. Recruitment in RCFs is feasible. Definitive trials of deprescribing are required.

  16. Bayesian Enrichment Strategies for Randomized Discontinuation Trials

    PubMed Central

    Trippa, Lorenzo; Rosner, Gary L.; Müller, Peter

    2013-01-01

    Summary We propose optimal choice of the design parameters for random discontinuation designs (RDD) using a Bayesian decision-theoretic approach. We consider applications of RDDs to oncology phase II studies evaluating activity of cytostatic agents. The design consists of two stages. The preliminary open-label stage treats all patients with the new agent and identifies a possibly sensitive subpopulation. The subsequent second stage randomizes, treats, follows, and compares outcomes among patients in the identified subgroup, with randomization to either the new or a control treatment. Several tuning parameters characterize the design: the number of patients in the trial, the duration of the preliminary stage, and the duration of follow-up after randomization. We define a probability model for tumor growth, specify a suitable utility function, and develop a computational procedure for selecting the optimal tuning parameters. PMID:21714780

  17. Randomized controlled trials - a matter of design.

    PubMed

    Spieth, Peter Markus; Kubasch, Anne Sophie; Penzlin, Ana Isabel; Illigens, Ben Min-Woo; Barlinn, Kristian; Siepmann, Timo

    2016-01-01

    Randomized controlled trials (RCTs) are the hallmark of evidence-based medicine and form the basis for translating research data into clinical practice. This review summarizes commonly applied designs and quality indicators of RCTs to provide guidance in interpreting and critically evaluating clinical research data. It further reflects on the principle of equipoise and its practical applicability to clinical science with an emphasis on critical care and neurological research. We performed a review of educational material, review articles, methodological studies, and published clinical trials using the databases MEDLINE, PubMed, and ClinicalTrials.gov. The most relevant recommendations regarding design, conduction, and reporting of RCTs may include the following: 1) clinically relevant end points should be defined a priori, and an unbiased analysis and report of the study results should be warranted, 2) both significant and nonsignificant results should be objectively reported and published, 3) structured study design and performance as indicated in the Consolidated Standards of Reporting Trials statement should be employed as well as registration in a public trial database, 4) potential conflicts of interest and funding sources should be disclaimed in study report or publication, and 5) in the comparison of experimental treatment with standard care, preplanned interim analyses during an ongoing RCT can aid in maintaining clinical equipoise by assessing benefit, harm, or futility, thus allowing decision on continuation or termination of the trial.

  18. Cluster randomized trials for pharmacy practice research.

    PubMed

    Gums, Tyler; Carter, Barry; Foster, Eric

    2016-06-01

    Introduction Cluster randomized trials (CRTs) are now the gold standard in health services research, including pharmacy-based interventions. Studies of behaviour, epidemiology, lifestyle modifications, educational programs, and health care models are utilizing the strengths of cluster randomized analyses. Methodology The key property of CRTs is the unit of randomization (clusters), which may be different from the unit of analysis (individual). Subject sample size and, ideally, the number of clusters is determined by the relationship of between-cluster and within-cluster variability. The correlation among participants recruited from the same cluster is known as the intraclass correlation coefficient (ICC). Generally, having more clusters with smaller ICC values will lead to smaller sample sizes. When selecting clusters, stratification before randomization may be useful in decreasing imbalances between study arms. Participant recruitment methods can differ from other types of randomized trials, as blinding a behavioural intervention cannot always be done. When to use CRTs can yield results that are relevant for making "real world" decisions. CRTs are often used in non-therapeutic intervention studies (e.g. change in practice guidelines). The advantages of CRT design in pharmacy research have been avoiding contamination and the generalizability of the results. A large CRT that studied physician-pharmacist collaborative management of hypertension is used in this manuscript as a CRT example. The trial, entitled Collaboration Among Pharmacists and physicians To Improve Outcomes Now (CAPTION), was implemented in primary care offices in the United States for hypertensive patients. Limitations CRT design limitations include the need for a large number of clusters, high costs, increased training, increased monitoring, and statistical complexity.

  19. Propensity score matching in randomized clinical trials.

    PubMed

    Xu, Zhenzhen; Kalbfleisch, John D

    2010-09-01

    Cluster randomization trials with relatively few clusters have been widely used in recent years for evaluation of health-care strategies. On average, randomized treatment assignment achieves balance in both known and unknown confounding factors between treatment groups, however, in practice investigators can only introduce a small amount of stratification and cannot balance on all the important variables simultaneously. The limitation arises especially when there are many confounding variables in small studies. Such is the case in the INSTINCT trial designed to investigate the effectiveness of an education program in enhancing the tPA use in stroke patients. In this article, we introduce a new randomization design, the balance match weighted (BMW) design, which applies the optimal matching with constraints technique to a prospective randomized design and aims to minimize the mean squared error (MSE) of the treatment effect estimator. A simulation study shows that, under various confounding scenarios, the BMW design can yield substantial reductions in the MSE for the treatment effect estimator compared to a completely randomized or matched-pair design. The BMW design is also compared with a model-based approach adjusting for the estimated propensity score and Robins-Mark-Newey E-estimation procedure in terms of efficiency and robustness of the treatment effect estimator. These investigations suggest that the BMW design is more robust and usually, although not always, more efficient than either of the approaches. The design is also seen to be robust against heterogeneous error. We illustrate these methods in proposing a design for the INSTINCT trial.

  20. Alternatives to the Randomized Controlled Trial

    PubMed Central

    West, Stephen G.; Duan, Naihua; Pequegnat, Willo; Gaist, Paul; Des Jarlais, Don C.; Holtgrave, David; Szapocznik, José; Fishbein, Martin; Rapkin, Bruce; Clatts, Michael; Mullen, Patricia Dolan

    2008-01-01

    Public health researchers are addressing new research questions (e.g., effects of environmental tobacco smoke, Hurricane Katrina) for which the randomized controlled trial (RCT) may not be a feasible option. Drawing on the potential outcomes framework (Rubin Causal Model) and Campbellian perspectives, we consider alternative research designs that permit relatively strong causal inferences. In randomized encouragement designs, participants are randomly invited to participate in one of the treatment conditions, but are allowed to decide whether to receive treatment. In quantitative assignment designs, treatment is assigned on the basis of a quantitative measure (e.g., need, merit, risk). In observational studies, treatment assignment is unknown and presumed to be nonrandom. Major threats to the validity of each design and statistical strategies for mitigating those threats are presented. PMID:18556609

  1. Randomization methods in emergency setting trials: a descriptive review

    PubMed Central

    Moe‐Byrne, Thirimon; Oddie, Sam; McGuire, William

    2015-01-01

    Background Quasi‐randomization might expedite recruitment into trials in emergency care settings but may also introduce selection bias. Methods We searched the Cochrane Library and other databases for systematic reviews of interventions in emergency medicine or urgent care settings. We assessed selection bias (baseline imbalances) in prognostic indicators between treatment groups in trials using true randomization versus trials using quasi‐randomization. Results Seven reviews contained 16 trials that used true randomization and 11 that used quasi‐randomization. Baseline group imbalance was identified in four trials using true randomization (25%) and in two quasi‐randomized trials (18%). Of the four truly randomized trials with imbalance, three concealed treatment allocation adequately. Clinical heterogeneity and poor reporting limited the assessment of trial recruitment outcomes. Conclusions We did not find strong or consistent evidence that quasi‐randomization is associated with selection bias more often than true randomization. High risk of bias judgements for quasi‐randomized emergency studies should therefore not be assumed in systematic reviews. Clinical heterogeneity across trials within reviews, coupled with limited availability of relevant trial accrual data, meant it was not possible to adequately explore the possibility that true randomization might result in slower trial recruitment rates, or the recruitment of less representative populations. © 2015 The Authors. Research Synthesis Methods published by John Wiley & Sons, Ltd. PMID:26333419

  2. Recent randomized controlled trials in otolaryngology.

    PubMed

    Banglawala, Sarfaraz M; Lawrence, Lauren A; Franko-Tobin, Emily; Soler, Zachary M; Schlosser, Rodney J; Ioannidis, John

    2015-03-01

    To assess recent trends in the prevalence and quality of reporting of randomized controlled trials (RCTs) in 4 otolaryngology journals. Methodology and reporting analysis. Randomized controlled trials in 4 otolaryngology journals. All RCTs published from 2011 to 2013 in 4 major otolaryngology journals were examined for characteristics of study design, quality of design and reporting, and funding. Of 5279 articles published in 4 leading otolaryngology journals from 2011 to 2013, 189 (3.3%) were RCTs. The majority of RCTs were clinical studies (86%), with the largest proportion consisting of sinonasal topics (31%). Most interventions were medical (46%), followed by surgical (38%) and mixed (16%). In terms of quality, randomization method was reported in 54% of RCTs, blinding in 33%, and adverse events in 65%. Intention-to-treat analysis was used in 32%; P values were reported in 87% and confidence intervals in 10%. Research funding was most often absent or not reported (55%), followed by not-for-profit (25%). Based on review of 4 otolaryngology journals, RCTs are still a small proportion of all published studies in the field of otolaryngology. There seem to be trends toward improvement in quality of design and reporting of RCTs, although many quality features remain suboptimal. Practitioners both designing and interpreting RCTs should critically evaluate RCTs for quality. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

  3. Conducting randomized trials in general practice: methodological and practical issues.

    PubMed Central

    Ward, E; King, M; Lloyd, M; Bower, P; Friedli, K

    1999-01-01

    The evaluation of the outcome of health services technologies is a requirement for their efficient provision in clinical practice. The most reliable evidence for treatment efficacy comes from randomized trials. Randomized trials in general practice pose particular methodological and practical difficulties. In this paper, we discuss how best to plan and manage a clinical trial in this setting. We base our discussion on our experience of conducting randomized trials to evaluate the effectiveness of brief psychotherapy in general practice. PMID:10818663

  4. Randomized Control Trial of Composite Cuspal Restorations

    PubMed Central

    Fennis, W.M.; Kuijs, R.H.; Roeters, F.J.; Creugers, N.H.; Kreulen, C.M.

    2014-01-01

    The objective of this randomized control trial was to compare the five-year clinical performance of direct and indirect resin composite restorations replacing cusps. In 157 patients, 176 restorations were made to restore maxillary premolars with Class II cavities and one missing cusp. Ninety-two direct and 84 indirect resin composite restorations were placed by two operators, following a strict protocol. Treatment technique and operator were assigned randomly. Follow-up period was at least 4.5 yrs. Survival rates were determined with time to reparable failure and complete failure as endpoints. Kaplan-Meier five-year survival rates were 86.6% (SE 0.27%) for reparable failure and 87.2% (SE 0.27%) for complete failure. Differences between survival rates of direct and indirect restorations [89.9% (SE 0.34%) vs. 83.2% (SE 0.42%) for reparable failure and 91.2% (SE 0.32%) vs. 83.2% (SE 0.42%) for complete failure] were not statistically significant (p = .23 for reparable failure; p = .15 for complete failure). Mode of failure was predominantly adhesive. The results suggest that direct and indirect techniques provide comparable results over the long term (trial registration number: ISRCTN29200848). PMID:24155264

  5. Sham Electroacupuncture Methods in Randomized Controlled Trials

    PubMed Central

    Chen, Zi-xian; Li, Yan; Zhang, Xiao-guang; Chen, Shuang; Yang, Wen-ting; Zheng, Xia-wei; Zheng, Guo-qing

    2017-01-01

    Sham electroacupuncture (EA) control is commonly used to evaluate the specific effects of EA in randomized-controlled trials (RCTs). However, establishing an inert and concealable sham EA control remains methodologically challenging. Here, we aimed to systematically investigate the sham EA methods. Eight electronic databases were searched from their inception to April 2015. Ten out of the 17 sham EA methods were identified from 94 RCTs involving 6134 participants according to three aspects: needle location, depth of needle insertion and electrical stimulation. The top three most frequently used types were sham EA type A, type L and type O ordinally. Only 24 out of the 94 trials reported credibility tests in six types of sham EA methods and the results were mainly as follows: sham EA type A (10/24), type B (5/24) and type Q (5/24). Compared with sham EA controls, EA therapy in 56.2% trials reported the specific effects, of which the highest positive rate was observed in type N (3/4), type F (5/7), type D (4/6) and type M (2/3). In conclusion, several sham EA types were identified as a promising candidate for further application in RCTs. Nonetheless, more evidence for inert and concealable sham EA control methods is needed. PMID:28106094

  6. Randomized clinical trials in breast cancer.

    PubMed

    Crago, Aimee M; Azu, Michelle; Tierney, Shannon; Morrow, Monica

    2010-01-01

    Breast cancer remains the most common cancer diagnosed in women and the second leading cause of cancer-related deaths in this group. Significant advances in the treatment of breast cancer and in the ability to screen for the disease mean that it is also one of the most curable forms of cancer. Long-term updates of the trials reviewed in the previous edition of this article have demonstrated that breast-conserving therapy remains a viable option for most patients, and that local control is related to overall survival. New chemotherapeutic options and endocrine therapies are available to select subsets of patients, and the use of endocrine therapy in breast cancer prevention has been shown to be of clear benefit. The sheer number of breast cancer-related randomized, controlled trials makes it impossible to review all level Ia evidence in this article but, where possible, extensive referencing and tabular review of related trials are used to provide the reader with a clear outline of the central data dictating current standard of care.

  7. 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

  8. Randomized clinical trial comparing two mastectomy techniques.

    PubMed

    Rodd, Caroline D; Velchuru, Vamsi R; Holly-Archer, Frances; Clark, Allan; Pereira, Jerome H

    2007-06-01

    The unit was considering the routine use of diathermy scissors for standard mastectomy surgery. We therefore aimed to assess scientifically the outcome of patients following the use of this instrument in their operation before accepting it as a routine procedure. A single blind randomized control trial compared the outcome of patients undergoing simple mastectomy using either the standard scalpel blade technique or the bipolar cutting scissors technique. Each arm of the trial contained 30 patients. The two primary outcome measures were blood loss intraoperatively and the operating time. There was a significant difference between the two groups, with a statistically significant benefit in the scissors group in terms of the secondary outcome measures of chest wall clearance and skin flap development as assessments of surgical completeness of mastectomy. There is no evidence of any other secondary outcome measures differing between the treatment groups. There is strong evidence that using electric scissors reduces intraoperative blood loss and operating time. There is some evidence that the scissors may provide better surgical completeness of mastectomy.

  9. Enhancing adoptive parenting: a randomized controlled trial.

    PubMed

    Rushton, Alan; Monck, Elizabeth; Leese, Morven; McCrone, Paul; Sharac, Jessica

    2010-10-01

    The aim was to conduct a pragmatic randomized controlled trial (RCT) to evaluate two parenting programmes designed for adopters of children late placed from care. Adoptive parents, with children between 3 and 8 years who were screened to have serious behavioural problems early in the placement, participated in home-based, manualized, parenting programmes delivered by trained and supervised family social workers. The adopters who agreed to join the study were randomly allocated to one of two parenting interventions or to a "services as usual" group. Baseline, immediate post-intervention and six-month follow-ups were assessed using questionnaires and adopter interviews. No cases were lost to follow-up at any point and satisfaction was high with both parenting interventions. At the six-month follow-up, a significant difference (p < 0.007) was found for "satisfaction with parenting" in favour of the intervention group (Effect Size d = 0.7). Negative parenting approaches were reduced in the intervention group. However, no significant differences in child problems were found between the intervention groups and control group, adjusting for baseline scores. Costs analysis showed that a relatively modest investment in post-adoption support would be well spent in improving adopters' satisfaction with parenting in the intervention group compared to the routine service group.

  10. Balancing multiple baseline characteristics in randomized clinical trials.

    PubMed

    Su, Zheng

    2011-07-01

    It is of vital importance to the success of a randomized clinical trial to maintain the balance of baseline characteristics (covariates) that could potentially confound the outcomes of the trial. Various randomization methods have been proposed to increase the likelihood of having balanced covariates at the end of a trial, most of which only apply to categorical covariates. An optimization approach to maintaining the balance of multiple covariates in randomized clinical trials is proposed, which is applicable to both continuous and categorical covariates and allows the covariates to be ranked according to their clinical importance as perceived by the clinical trial practitioners. Simulation results show that the proposed algorithm significantly outperforms the standard randomization approach via flipping an unbiased coin. The proposed randomization method can be easily implemented and generalized for cases where there are multiple treatment arms with equal or unequal randomization probabilities. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Randomized Trial of Thymectomy in Myasthenia Gravis.

    PubMed

    Wolfe, Gil I; Kaminski, Henry J; Aban, Inmaculada B; Minisman, Greg; Kuo, Hui-Chien; Marx, Alexander; Ströbel, Philipp; Mazia, Claudio; Oger, Joel; Cea, J Gabriel; Heckmann, Jeannine M; Evoli, Amelia; Nix, Wilfred; Ciafaloni, Emma; Antonini, Giovanni; Witoonpanich, Rawiphan; King, John O; Beydoun, Said R; Chalk, Colin H; Barboi, Alexandru C; Amato, Anthony A; Shaibani, Aziz I; Katirji, Bashar; Lecky, Bryan R F; Buckley, Camilla; Vincent, Angela; Dias-Tosta, Elza; Yoshikawa, Hiroaki; Waddington-Cruz, Márcia; Pulley, Michael T; Rivner, Michael H; Kostera-Pruszczyk, Anna; Pascuzzi, Robert M; Jackson, Carlayne E; Garcia Ramos, Guillermo S; Verschuuren, Jan J G M; Massey, Janice M; Kissel, John T; Werneck, Lineu C; Benatar, Michael; Barohn, Richard J; Tandan, Rup; Mozaffar, Tahseen; Conwit, Robin; Odenkirchen, Joanne; Sonett, Joshua R; Jaretzki, Alfred; Newsom-Davis, John; Cutter, Gary R

    2016-08-11

    Thymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. We conducted a multicenter, randomized trial comparing thymectomy plus prednisone with prednisone alone. We compared extended transsternal thymectomy plus alternate-day prednisone with alternate-day prednisone alone. Patients 18 to 65 years of age who had generalized nonthymomatous myasthenia gravis with a disease duration of less than 5 years were included if they had Myasthenia Gravis Foundation of America clinical class II to IV disease (on a scale from I to V, with higher classes indicating more severe disease) and elevated circulating concentrations of acetylcholine-receptor antibody. The primary outcomes were the time-weighted average Quantitative Myasthenia Gravis score (on a scale from 0 to 39, with higher scores indicating more severe disease) over a 3-year period, as assessed by means of blinded rating, and the time-weighted average required dose of prednisone over a 3-year period. A total of 126 patients underwent randomization between 2006 and 2012 at 36 sites. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a 3-year period than those who received prednisone alone (6.15 vs. 8.99, P<0.001); patients in the thymectomy group also had a lower average requirement for alternate-day prednisone (44 mg vs. 60 mg, P<0.001). Fewer patients in the thymectomy group than in the prednisone-only group required immunosuppression with azathioprine (17% vs. 48%, P<0.001) or were hospitalized for exacerbations (9% vs. 37%, P<0.001). The number of patients with treatment-associated complications did not differ significantly between groups (P=0.73), but patients in the thymectomy group had fewer treatment-associated symptoms related to immunosuppressive medications (P<0.001) and lower distress levels related to symptoms (P=0.003). Thymectomy improved clinical outcomes over a 3-year period in

  12. Randomized Trial of Thymectomy in Myasthenia Gravis

    PubMed Central

    Wolfe, G.I.; Kaminski, H.J.; Aban, I.B.; Minisman, G.; Kuo, H.-C.; Marx, A.; Ströbel, P.; Mazia, C.; Oger, J.; Cea, J.G.; Heckmann, J.M.; Evoli, A.; Nix, W.; Ciafaloni, E.; Antonini, G.; Witoonpanich, R.; King, J.O.; Beydoun, S.R.; Chalk, C.H.; Barboi, A.C.; Amato, A.A.; Shaibani, A.I.; Katirji, B.; Lecky, B.R.F.; Buckley, C.; Vincent, A.; Dias-Tosta, E.; Yoshikawa, H.; Waddington-Cruz, M.; Pulley, M.T.; Rivner, M.H.; Kostera-Pruszczyk, A.; Pascuzzi, R.M.; Jackson, C.E.; Ramos, G.S. Garcia; Verschuuren, J.J.G.M.; Massey, J.M.; Kissel, J.T.; Werneck, L.C.; Benatar, M.; Barohn, R.J.; Tandan, R.; Mozaffar, T.; Conwit, R.; Odenkirchen, J.; Sonett, J.R.; Jaretzki, A.; Newsom-Davis, J.; Cutter, G.R.

    2016-01-01

    BACKGROUND Thymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. We conducted a multicenter, randomized trial comparing thymectomy plus prednisone with prednisone alone. METHODS We compared extended transsternal thymectomy plus alternate-day prednisone with alternate-day prednisone alone. Patients 18 to 65 years of age who had generalized nonthymomatous myasthenia gravis with a disease duration of less than 5 years were included if they had Myasthenia Gravis Foundation of America clinical class II to IV disease (on a scale from I to V, with higher classes indicating more severe disease) and elevated circulating concentrations of acetylcholine-receptor antibody. The primary outcomes were the time-weighted average Quantitative Myasthenia Gravis score (on a scale from 0 to 39, with higher scores indicating more severe disease) over a 3-year period, as assessed by means of blinded rating, and the time-weighted average required dose of prednisone over a 3-year period. RESULTS A total of 126 patients underwent randomization between 2006 and 2012 at 36 sites. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a 3-year period than those who received prednisone alone (6.15 vs. 8.99, P<0.001); patients in the thymectomy group also had a lower average requirement for alternate-day prednisone (44 mg vs. 60 mg, P<0.001). Fewer patients in the thymectomy group than in the prednisone-only group required immunosuppression with azathioprine (17% vs. 48%, P<0.001) or were hospitalized for exacerbations (9% vs. 37%, P<0.001). The number of patients with treatment-associated complications did not differ significantly between groups (P=0.73), but patients in the thymectomy group had fewer treatment-associated symptoms related to immunosuppressive medications (P<0.001) and lower distress levels related to symptoms (P=0.003). CONCLUSIONS Thymectomy improved

  13. A Framework for Designing Cluster Randomized Trials with Binary Outcomes

    ERIC Educational Resources Information Center

    Spybrook, Jessaca; Martinez, Andres

    2011-01-01

    The purpose of this paper is to provide a frame work for approaching a power analysis for a CRT (cluster randomized trial) with a binary outcome. The authors suggest a framework in the context of a simple CRT and then extend it to a blocked design, or a multi-site cluster randomized trial (MSCRT). The framework is based on proportions, an…

  14. ADULTS: A RANDOMIZED CONTROLLED CLINICAL TRIAL

    PubMed Central

    Shah, Krupa N.; Majeed, Zahraa; Yoruk, Yilmaz B.; Yang, Hongmei; Hilton, Tiffany N.; McMahon, James M.; Hall, William J.; Walck, Donna; Luque, Amneris E.; Ryan, Richard M.

    2016-01-01

    Objective HIV-infected older adults (HOA) are at risk of functional decline. Interventions promoting physical activity that can attenuate functional decline and are easily translated into the HOA community are of high priority. We conducted a randomized, controlled clinical trial to evaluate whether a physical activity counseling intervention based on self-determination theory (SDT) improves physical function, autonomous motivation, depression and the quality of life (QOL) in HOA. Methods A total of 67 community-dwelling HOA with mild-to-moderate functional limitations were randomized to one of two groups: a physical activity counseling group or the usual care control group. We used SDT to guide the development of the experimental intervention. Outcome measures that were collected at baseline and final study visits included a battery of physical function tests, levels of physical activity, autonomous motivation, depression, and QOL. Results The study participants were similar in their demographic and clinical characteristics in both the treatment and control groups. Overall physical performance, gait speed, measures of endurance and strength, and levels of physical activity improved in the treatment group compared to the control group (p<0.05). Measures of autonomous regulation such as identified regulation, and measures of depression and QOL improved significantly in the treatment group compared to the control group (p<0.05). Across the groups, improvement in intrinsic regulation and QOL correlated with an improvement in physical function (p<0.05). Conclusion Our findings suggest that a physical activity counseling program grounded in SDT can improve physical function, autonomous motivation, depression, and QOL in HOA with functional limitations. PMID:26867045

  15. Family Maltreatment, Substance Problems, and Suicidality: Randomized Prevention Effectiveness Trial

    DTIC Science & Technology

    2008-02-01

    another institution? NO YES → Is it a multi-center clinical trial (e.g., Oncology Group, ACTG, Industry-initiated)? YES NO → Provide name(s...NO YES → You must comply with the clinical trial registration requirements detailed at http://www.stonybrook.edu/research/humans...and Suicidality: Randomized Prevention Effectiveness Trial PRINCIPAL INVESTIGATOR: Richard E. Heyman, Ph.D

  16. Pediatric Nephrologists’ Beliefs Regarding Randomized Controlled Trials

    PubMed Central

    Wightman, Aaron G; Oron, Assaf P; Symons, Jordan M; Flynn, Joseph T

    2014-01-01

    Background Pediatrics and pediatric nephrology lag behind adult medicine in producing randomized controlled trials (RCTs). Physician attitudes have been shown to play a significant role in RCT enrollment. Methods We surveyed members of the American Society of Pediatric Nephrology regarding beliefs about RCTs and factors influencing decisions to recommend RCT enrollment. Regression analyses were used to identify effects of variables on an aggregate score summarizing attitudes toward RCTs. Results 130 replies were received. 66% had enrolled patients in RCTs. Respondents in practice >15 years were more likely to have recruited a patient to a RCT than those in practice <5 years. Respondents were more willing to recommend RCT enrollment if the study was multicenter, patients were sicker or had a poorer prognosis, or if the parent or participant received a financial incentive versus the provider. In multiple regression analysis, history of enrolling patients in a RCT was the only significant predictor of higher aggregate RCT-friendly attitude. Conclusions Many pediatric nephrologists have never enrolled a patient in a RCT, particularly those in practice <5 years. Respondents who have not enrolled patients in RCTs have a less RCT-friendly attitude. Provision of improved training and resources might increase participation of junior providers in RCTs. PMID:24379023

  17. Randomized Trials in Emergency Medicine Journals, 2008-2011

    PubMed Central

    Jones, Christopher W.; Hunold, Katherine M.; Isaacs, Cameron G.; Platts-Mills, Timothy F.

    2012-01-01

    Study Objective Knowledge of current areas of activity in emergency medicine research may improve collaboration among investigators and may help inform decisions about future research priorities. Randomized controlled trials are a key component of research activity and an essential tool for improving care. We investigated the characteristics of randomized trials recently published in emergency medicine journals. Methods This was a retrospective analysis of randomized trials published in the five highest-impact emergency medicine journals. Pubmed was searched for reports of randomized trials involving human subjects indexed to MEDLINE between January 1, 2008 and December 31, 2011. Included trials were classified with respect to study topic, funding source, presence of age-related inclusion criteria, and country of origin. Results 163 published studies were included for analysis. Pain management was the most commonly studied topic (N=28, 17%) followed by orthopedics (N = 24, 15%), cardiovascular disease (N=13, 8%), and pre-hospital medicine (N=13, 8%). Less than half of studies received extramural funding support. Children were specifically examined in 22 (13%) of trials; only 5 trials (3%) specifically examined patients age 60 or older. Conclusions Emergency medicine journals publish randomized trials addressing a wide range of clinical topics. Randomized trials focusing on geriatric patients are not commonly published in these journals. PMID:22867836

  18. Nurses' unique roles in randomized clinical trials.

    PubMed

    Sadler, G R; Lantz, J M; Fullerton, J T; Dault, Y

    1999-01-01

    Nurses are in an ideal position to promote patients' awareness of the role played by clinical trials in the advancement of health science and the subsequent improvement of patient care. The history of clinical trials and the four phases of clinical trials are described. Nurses' professional roles in clinical trial participation, such as helping the patient to identify open clinical trials and acting as clinical interpreter and patient advocate during the patient's participation in a trial, are detailed. Professional considerations that must be addressed by the nurse are reviewed and include ensuring that the trial has received approval from an Institutional Review Board for the participation of human subjects; that the responsibilities of participation are congruent with the nurse's personal values and workplace obligations; and that once engaged, the nurse can make the commitment to sustain participation in the trial. Most important, the nurse must keep the patient's needs and values uppermost in mind during the evaluation of potential clinical trials. Nurses have a critical role to play in the promotion of clinical trials, the recruitment of patients for clinical trial participation, the education of the patient and family, and the clinical care and support of patients throughout their participation in clinical trials.

  19. 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

  20. Randomized controlled trials: still the backbone of vascular surgery?

    PubMed

    Naylor, A R

    Prior to the introduction of evidence-based medicine, decision-making was largely based upon 'intuitive reasoning', whereby senior clinicians dictated practice based upon personal dogma, personal experience and (often) biased observational studies. This era began to end (in vascular surgery) following completion of the landmark randomized trials in carotid disease, which recruited patients throughout the 1980s. Despite scepticism amongst some surgeons of the time these particular randomized trials have stood the test of time and remain the cornerstone of virtually every guideline of practice to this day. The carotid randomized trials became a beacon for using 'evidence' rather than 'intuitive reasoning' and randomized trials have now been used to determine optimal practice in a plethora of carotid surgery and stenting trials, lower limb revascularization and numerous aortic aneurysm based studies. The literature abounds with situations where practice (previously based on observational study data) was changed overnight following publication of a well-designed randomized trial. However, while observational studies are prone to selection bias, randomized trials bring their own unique limitations including problems with external validity, they take too long to complete, they are very expensive, they are notorious for problems with recruitment and they can frequently become obsolete. This has led to a (not unreasonable) call for more observational studies to be used in the development of practice guidelines. Unfortunately, the principle guideline bodies around the world, e.g. National Institute for Health and Care Excellence (NICE) and the American Heart Association (AHA), prioritize randomized trial evidence above all else. Until that changes, guideline makers will find it very difficult to deviate from using historical randomized trial evidence, even when high quality observational data suggest that 'real world' practice bears little comparison to that reported in the

  1. Registering Randomized Clinical Trials and the Case for CONSORT

    PubMed Central

    Elliott, Timothy R.

    2008-01-01

    Recent controversies in medical research and the increasing reliance on randomized clinical trials to inform evidence-based practice have prompted coordinated attempts to standardize reporting and register information about trials for consistency and transparency. The Consolidated Standards of Reporting Trials guidelines (D. G. Altman et al., 2001) and trial registry are described in this article, and the implications for clinical and experimental research in psychopharmacology are discussed. PMID:18179303

  2. A Randomized Trial of Motivational Interviewing

    PubMed Central

    Catley, Delwyn; Goggin, Kathy; Harris, Kari Jo; Richter, Kimber P.; Williams, Karen; Patten, Christi; Resnicow, Ken; Ellerbeck, Edward F.; Bradley-Ewing, Andrea; Lee, Hyoung S.; Moreno, Jose L.; Grobe, James E.

    2015-01-01

    Introduction Despite limitations in evidence, the current Clinical Practice Guideline advocates Motivational Interviewing for smokers not ready to quit. This study evaluated the efficacy of Motivational Interviewing (MI) for inducing cessation-related behaviors among smokers with low motivation to quit. Design Randomized clinical trial. Setting/participants Two-hundred fifty-five daily smokers reporting low desire to quit smoking were recruited from an urban community during 2010–2011 and randomly assigned to Motivational Interviewing, health education, or brief advice using a 2:2:1 allocation. Data were analyzed from 2012 to 2014. Intervention Four sessions of Motivational Interviewing utilized a patient-centered communication style that explored patients’ own reasons for change. Four sessions of health education provided education related to smoking cessation while excluding elements characteristic of Motivational Interviewing. A single session of brief advice consisted of brief, personalized advice to quit. Main outcomes measures Self-reported quit attempts, smoking abstinence (biochemically verified), use of cessation pharmacotherapies, motivation, and confidence to quit were assessed at baseline and 3- and 6-month follow-ups. Results Unexpectedly, no significant differences emerged between groups in the proportion who made a quit attempt by 6-month follow-up (Motivational Interviewing, 52.0%; health education, 60.8%; brief advice, 45.1%; p=0.157). Health education had significantly higher biochemically verified abstinence rates at 6 months (7.8%) than brief advice (0.0%) (8% difference, 95% CI=3%, 13%, p=0.003), with the Motivational Interviewing group falling in between (2.9% abstinent, 3% risk difference, 95% CI=0%, 6%, p=0.079). Both Motivational Interviewing and health education groups showed greater increases in cessation medication use, motivation, and confidence to quit relative to brief advice (all p<0.05), and health education showed greater

  3. Ethics of randomized clinical trials and the 'ALARA' approach.

    PubMed

    Zwitter, M

    1999-01-01

    A balanced discussion on the ethics of randomized clinical trials should not be based on a single ethical aspect such as respect for the patient's autonomy. Rather, the analysis should consider the four ethical principles--respect for autonomy, non-maleficence, beneficence, and justice--as applicable to all groups of persons concerned. We present the ethical benefits and costs of the present practice of randomized clinical trials for four groups: patients involved in clinical trials, patients not involved in trials, participating physicians and society. The ALARA (As Low As Reasonably Achievable) approach is then introduced and practical measures to achieve a positive balance between ethical benefits and costs of randomized trials are proposed.

  4. Analytic Methods for Individually Randomized Group Treatment Trials and Group-Randomized Trials When Subjects Belong to Multiple Groups

    PubMed Central

    Andridge, Rebecca. R.; Shoben, Abigail B.; Muller, Keith E.; Murray, David M.

    2014-01-01

    Participants in trials may be randomized either individually or in groups, and may receive their treatment either entirely individually, entirely in groups, or partially individually and partially in groups. This paper concerns cases in which participants receive their treatment either entirely or partially in groups, regardless of how they were randomized. Participants in Group-Randomized Trials (GRTs) are randomized in groups and participants in Individually Randomized Group Treatment (IRGT) trials are individually randomized, but participants in both types of trials receive part or all of their treatment in groups or through common change agents. Participants who receive part or all of their treatment in a group are expected to have positively correlated outcome measurements. This paper addresses a situation that occurs in GRTs and IRGT trials – participants receive treatment through more than one group. As motivation, we consider trials in The Childhood Obesity Prevention and Treatment Research Consortium (COPTR), in which each child participant receives treatment in at least two groups. In simulation studies we considered several possible analytic approaches over a variety of possible group structures. A mixed model with random effects for both groups provided the only consistent protection against inflated type I error rates and did so at the cost of only moderate loss of power when intraclass correlations were not large. We recommend constraining variance estimates to be positive and using the Kenward-Roger adjustment for degrees of freedom; this combination provided additional power but maintained type I error rates at the nominal level. PMID:24399701

  5. Quality assessment of randomized clinical trial in intensive care.

    PubMed

    Gonçalves, Giulliano Peixoto; Barbosa, Fabiano Timbó; Barbosa, Luciano Timbó; Duarte, José Lira

    2009-03-01

    A randomized clinical trial is a prospective study that compares the effect and value of interventions in human beings, of one or more groups vs. a control group. The objective of this study was to evaluate the quality of published randomized clinical trials in Intensive care in Brazil. All randomized clinical trials in intensive care found by manual search in Revista Brasileira de Terapia Intensiva from January 2001 to March 2008 were assessed to evaluate their description by the quality scale. Descriptive statistics and a 95 % confidence interval were used for the primary outcome. Our primary outcome was the randomized clinical trial quality. Our search found 185 original articles, of which 14 were randomized clinical trials. Only one original article (7.1%) showed good quality. There was no statistical significance between the collected data and the data shown in the hypothesis of this search. It can be concluded that in the sample of assessed articles 7% of the randomized clinical trials in intensive care published in a single intensive care journal in Brazil, present good methodological quality.

  6. Estimating the causal effect of randomization versus treatment preference in a doubly randomized preference trial.

    PubMed

    Marcus, Sue M; Stuart, Elizabeth A; Wang, Pei; Shadish, William R; Steiner, Peter M

    2012-06-01

    Although randomized studies have high internal validity, generalizability of the estimated causal effect from randomized clinical trials to real-world clinical or educational practice may be limited. We consider the implication of randomized assignment to treatment, as compared with choice of preferred treatment as it occurs in real-world conditions. Compliance, engagement, or motivation may be better with a preferred treatment, and this can complicate the generalizability of results from randomized trials. The doubly randomized preference trial (DRPT) is a hybrid randomized and nonrandomized design that allows for estimation of the causal effect of randomization versus treatment preference. In the DRPT, individuals are first randomized to either randomized assignment or choice assignment. Those in the randomized assignment group are then randomized to treatment or control, and those in the choice group receive their preference of treatment versus control. Using the potential outcomes framework, we apply the algebra of conditional independence to show how the DRPT can be used to derive an unbiased estimate of the causal effect of randomization versus preference for each of the treatment and comparison conditions. Also, we show how these results can be implemented using full matching on the propensity score. The methodology is illustrated with a DRPT of introductory psychology students who were randomized to randomized assignment or preference of mathematics versus vocabulary training. We found a small to moderate benefit of preference versus randomization with respect to the mathematics outcome for those who received mathematics training.

  7. European randomized lung cancer screening trials: Post NLST.

    PubMed

    Field, John K; van Klaveren, Rob; Pedersen, Jesper H; Pastorino, Ugo; Paci, Eugino; Becker, Nikolauss; Infante, Maurizo; Oudkerk, Matthijs; de Koning, Harry J

    2013-10-01

    Overview of the European randomized lung cancer CT screening trials (EUCT) is presented with regard to the implementation of CT screening in Europe; post NLST. All seven principal investigators completed a questionnaire on the epidemiological, radiological, and nodule management aspects of their trials at August 2010, which included 32,000 people, inclusion of UKLS pilot trial will reach 36,000. An interim analysis is planned, but the final mortality data testing is scheduled for 2015.

  8. Estimating the Causal Effect of Randomization versus Treatment Preference in a Doubly Randomized Preference Trial

    ERIC Educational Resources Information Center

    Marcus, Sue M.; Stuart, Elizabeth A.; Wang, Pei; Shadish, William R.; Steiner, Peter M.

    2012-01-01

    Although randomized studies have high internal validity, generalizability of the estimated causal effect from randomized clinical trials to real-world clinical or educational practice may be limited. We consider the implication of randomized assignment to treatment, as compared with choice of preferred treatment as it occurs in real-world…

  9. Stochastic inequality probabilities for adaptively randomized clinical trials.

    PubMed

    Cook, John D; Nadarajah, Saralees

    2006-06-01

    We examine stochastic inequality probabilities of the form P (X > Y) and P (X > max (Y, Z)) where X, Y, and Z are random variables with beta, gamma, or inverse gamma distributions. We discuss the applications of such inequality probabilities to adaptively randomized clinical trials as well as methods for calculating their values.

  10. Power Analysis of Cutoff-Based Randomized Clinical Trials.

    ERIC Educational Resources Information Center

    Cappelleri, Joseph C.; And Others

    1994-01-01

    A statistical power algorithm based on the Fisher Z method is developed for cutoff-based random clinical trials and the single cutoff-point (regression-discontinuity) design that has no randomization. This article quantifies power and sample size estimates for various levels of power and cutoff-based assignment. (Author/SLD)

  11. Summer School Effects in a Randomized Field Trial

    ERIC Educational Resources Information Center

    Zvoch, Keith; Stevens, Joseph J.

    2013-01-01

    This field-based randomized trial examined the effect of assignment to and participation in summer school for two moderately at-risk samples of struggling readers. Application of multiple regression models to difference scores capturing the change in summer reading fluency revealed that kindergarten students randomly assigned to summer school…

  12. Power Calculations for Binary Moderator in Cluster Randomized Trials

    ERIC Educational Resources Information Center

    Spybrook, Jessaca; Kelcey, Ben

    2014-01-01

    Cluster randomized trials (CRTs), or studies in which intact groups of individuals are randomly assigned to a condition, are becoming more common in the evaluation of educational programs, policies, and practices. The website for the National Center for Education Evaluation and Regional Assistance (NCEE) reveals they have launched over 30…

  13. The Changing Landscape of Randomized Clinical Trials in Cardiovascular Disease.

    PubMed

    Jones, W Schuyler; Roe, Matthew T; Antman, Elliott M; Pletcher, Mark J; Harrington, Robert A; Rothman, Russell L; Oetgen, William J; Rao, Sunil V; Krucoff, Mitchell W; Curtis, Lesley H; Hernandez, Adrian F; Masoudi, Frederick A

    2016-10-25

    Large randomized clinical trials in cardiovascular disease have proliferated over the past 3 decades, with results that have influenced every aspect of cardiology practice. Despite these advances, there remains a substantial need for more high-quality evidence to inform cardiovascular clinical practice, given the increasing prevalence of cardiovascular disease around the world. Traditional clinical trials are increasingly challenging due to rising costs, increasing complexity and length, and burdensome institutional and regulatory requirements. This review will examine the current landscape of cardiovascular clinical trials in the United States, highlight recently conducted registry-based clinical trials, and discuss the potential attributes of the recently launched pragmatic clinical trial by the Patient-Centered Outcomes Research Institute's National Patient-Centered Clinical Research Network, called the ADAPTABLE (Aspirin Dosing: A Patient-centric Trial Assessing the Benefits and Long-term Effectiveness) trial.

  14. Beyond HERS: some (not so) random thoughts on randomized clinical trials.

    PubMed

    Bush, T

    2001-01-01

    Science is the process of discovering truth, and "truth" is sampled each time we do a study. The results from all of our studies will be distributed around the truth, and different study designs give different amounts and different qualities of sampled material. Truth is ascertained only when sufficient numbers of appropriate studies are conducted, and no one study or one study design has a monopoly on truth. Currently, the randomized clinical trial is considered the penultimate study design and the ultimate test of the hypothesis, but only if it is double-blinded, placebo-controlled, and analyzed by an intention-to-treat protocol. The study design most similar to the randomized controlled trial is the prospective cohort study. In this observational approach, a cohort (group of individuals) is assembled and followed in real time while end points (e.g. breast cancers, heart attacks, fractures) accrue. This is contrasted to the randomized controlled trial, where a group of individuals is assembled, intervened upon, and followed in real time while end points accrue. The major advantage of the randomized controlled trial over an observational study is that the randomization process should eliminate any "bias" in the exposure of interest. However, the randomized controlled trial, like all study designs, has other limitations. Major limitations of the randomized controlled trial include significant financial and other costs, problems with external generalizability, the placebo effect, external monitoring, multi-center differences, and the (frequently problematic) intention-to-treat analysis rule. Many of these limitations do not occur in prospective cohort studies. For example, since a placebo is not administered in an observational study, there is no placebo effect, and since the study is not monitored by a data and safety monitoring board, abrupt truncation of the study duration is not usually seen in observational cohort studies. These limitations of randomized

  15. The Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial

    PubMed Central

    Eichhorn, Eric J; Bristow, Michael R

    2001-01-01

    Previous trials (Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure [MERIT-HF], Cardiac Insufficiency Bisoprolol Study [CIBIS] II) have demonstrated a mortality benefit of β-adrenergic blockade in patients with mild to moderate heart failure. The recent Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial has extended these results to a more advanced patient population. This trial did not, however, include patients who could not reach compensation, patients with far advanced heart failure symptoms, or a significant number of black patients. Future studies of β-blockade may focus on these patients or patients with asymptomatic left ventricular dysfunction. PMID:11806769

  16. The Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial.

    PubMed

    Eichhorn, Eric J; Bristow, Michael R

    2001-01-01

    Previous trials (Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure [MERIT-HF], Cardiac Insufficiency Bisoprolol Study [CIBIS] II) have demonstrated a mortality benefit of beta-adrenergic blockade in patients with mild to moderate heart failure. The recent Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial has extended these results to a more advanced patient population. This trial did not, however, include patients who could not reach compensation, patients with far advanced heart failure symptoms, or a significant number of black patients. Future studies of beta-blockade may focus on these patients or patients with asymptomatic left ventricular dysfunction.

  17. Methods for sample size determination in cluster randomized trials

    PubMed Central

    Rutterford, Clare; Copas, Andrew; Eldridge, Sandra

    2015-01-01

    Background: The use of cluster randomized trials (CRTs) is increasing, along with the variety in their design and analysis. The simplest approach for their sample size calculation is to calculate the sample size assuming individual randomization and inflate this by a design effect to account for randomization by cluster. The assumptions of a simple design effect may not always be met; alternative or more complicated approaches are required. Methods: We summarise a wide range of sample size methods available for cluster randomized trials. For those familiar with sample size calculations for individually randomized trials but with less experience in the clustered case, this manuscript provides formulae for a wide range of scenarios with associated explanation and recommendations. For those with more experience, comprehensive summaries are provided that allow quick identification of methods for a given design, outcome and analysis method. Results: We present first those methods applicable to the simplest two-arm, parallel group, completely randomized design followed by methods that incorporate deviations from this design such as: variability in cluster sizes; attrition; non-compliance; or the inclusion of baseline covariates or repeated measures. The paper concludes with methods for alternative designs. Conclusions: There is a large amount of methodology available for sample size calculations in CRTs. This paper gives the most comprehensive description of published methodology for sample size calculation and provides an important resource for those designing these trials. PMID:26174515

  18. Simple randomization did not protect against bias in smaller trials.

    PubMed

    Nguyen, Tri-Long; Collins, Gary S; Lamy, André; Devereaux, Philip J; Daurès, Jean-Pierre; Landais, Paul; Le Manach, Yannick

    2017-04-01

    By removing systematic differences across treatment groups, simple randomization is assumed to protect against bias. However, random differences may remain if the sample size is insufficiently large. We sought to determine the minimal sample size required to eliminate random differences, thereby allowing an unbiased estimation of the treatment effect. We reanalyzed two published multicenter, large, and simple trials: the International Stroke Trial (IST) and the Coronary Artery Bypass Grafting (CABG) Off- or On-Pump Revascularization Study (CORONARY). We reiterated 1,000 times the analysis originally reported by the investigators in random samples of varying size. We measured the covariates balance across the treatment arms. We estimated the effect of aspirin and heparin on death or dependency at 30 days after stroke (IST), and the effect of off-pump CABG on a composite primary outcome of death, nonfatal stroke, nonfatal myocardial infarction, or new renal failure requiring dialysis at 30 days (CORONARY). In addition, we conducted a series of Monte Carlo simulations of randomized trials to supplement these analyses. Randomization removes random differences between treatment groups when including at least 1,000 participants, thereby resulting in minimal bias in effects estimation. Later, substantial bias is observed. In a short review, we show such an enrollment is achieved in 41.5% of phase 3 trials published in the highest impact medical journals. Conclusions drawn from completely randomized trials enrolling a few participants may not be reliable. In these circumstances, alternatives such as minimization or blocking should be considered for allocating the treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Adaptive Designs for Randomized Trials in Public Health

    PubMed Central

    Brown, C. Hendricks; Have, Thomas R. Ten; Jo, Booil; Dagne, Getachew; Wyman, Peter A.; Muthén, Bengt; Gibbons, Robert D.

    2009-01-01

    In this article, we present a discussion of two general ways in which the traditional randomized trial can be modified or adapted in response to the data being collected. We use the term adaptive design to refer to a trial in which characteristics of the study itself, such as the proportion assigned to active intervention versus control, change during the trial in response to data being collected. The term adaptive sequence of trials refers to a decision-making process that fundamentally informs the conceptualization and conduct of each new trial with the results of previous trials. Our discussion below investigates the utility of these two types of adaptations for public health evaluations. Examples are provided to illustrate how adaptation can be used in practice. From these case studies, we discuss whether such evaluations can or should be analyzed as if they were formal randomized trials, and we discuss practical as well as ethical issues arising in the conduct of these new-generation trials. PMID:19296774

  20. Design and Validity of Randomized Controlled Dental Restorative Trials

    PubMed Central

    Göstemeyer, Gerd; Blunck, Uwe; Paris, Sebastian; Schwendicke, Falk

    2016-01-01

    Background: The evidence stemming from trials on restorative materials is shaped not only by trial findings, but also trial design and validity. We aimed to evaluate both aspects in randomized controlled dental restorative trials published from 2005–2015. Methods: Using systematic review methodology, we retrieved trials comparing restorative or adhesive dental materials. Two authors independently assessed design, risk of bias, registration status, and findings of trials. Descriptive and regression analyses were performed. Results: 114 studies on 15,321 restorations placed mainly in permanent teeth of 5232 patients were included. Per trial, the median number of patients was 37 (25th/75th percentiles: 30/51). Follow-up was 24 (20/48) months. Seventeen percent of trials reported on sample size calculations, 2% had been registered. Most trials (90%) used US Public Health Service (USPHS) criteria, and had a high risk of bias. More recent trials were more likely to have been registered, to have reported on sample size calculations, to be of low risk of bias, and to use other than USPHS-criteria. Twenty-three percent of trials yielded significant differences between groups. The likelihood of such differences was significantly increased in older studies, studies with potential reporting bias, published in journals with high impact factor (>2), longer follow-up periods, and not using USPHS-criteria. Conclusions: The majority of dental restorative trials published from 2005–2015 had limited validity. Risk of bias decreased in more recent trials. Future trials should aim for high validity, be registered, and use defined and appropriate sample sizes, follow-up periods, and outcome measures. PMID:28773493

  1. Initial Status in Growth Curve Modeling for Randomized Trials

    PubMed Central

    Chou, Chih-Ping; Chi, Felicia; Weisner, Constance; Pentz, MaryAnn; Hser, Yih-Ing

    2010-01-01

    The growth curve modeling (GCM) technique has been widely adopted in longitudinal studies to investigate progression over time. The simplest growth profile involves two growth factors, initial status (intercept) and growth trajectory (slope). Conventionally, all repeated measures of outcome are included as components of the growth profile, and the first measure is used to reflect the initial status. Selection of the initial status, however, can greatly influence study findings, especially for randomized trials. In this article, we propose an alternative GCM approach involving only post-intervention measures in the growth profile and treating the first wave after intervention as the initial status. We discuss and empirically illustrate how choices of initial status may influence study conclusions in addressing research questions in randomized trials using two longitudinal studies. Data from two randomized trials are used to illustrate that the alternative GCM approach proposed in this article offers better model fitting and more meaningful results. PMID:21572585

  2. Design of a cluster-randomized minority recruitment trial: RECRUIT.

    PubMed

    Tilley, Barbara C; Mainous, Arch G; Smith, Daniel W; McKee, M Diane; Amorrortu, Rossybelle P; Alvidrez, Jennifer; Diaz, Vanessa; Ford, Marvella E; Fernandez, Maria E; Hauser, Robert A; Singer, Carlos; Landa, Veronica; Trevino, Aron; DeSantis, Stacia M; Zhang, Yefei; Daniels, Elvan; Tabor, Derrick; Vernon, Sally W

    2017-06-01

    Racial/ethnic minority groups remain underrepresented in clinical trials. Many strategies to increase minority recruitment focus on minority communities and emphasize common diseases such as hypertension. Scant literature focuses on minority recruitment to trials of less common conditions, often conducted in specialty clinics and dependent on physician referrals. We identified trust/mistrust of specialist physician investigators and institutions conducting medical research and consequent participant reluctance to participate in clinical trials as key-shared barriers across racial/ethnic groups. We developed a trust-based continuous quality improvement intervention to build trust between specialist physician investigators and community minority-serving physicians and ultimately potential trial participants. To avoid the inherent biases of non-randomized studies, we evaluated the intervention in the national Randomized Recruitment Intervention Trial (RECRUIT). This report presents the design of RECRUIT. Specialty clinic follow-up continues through April 2017. We hypothesized that specialist physician investigators and coordinators trained in the trust-based continuous quality improvement intervention would enroll a greater proportion of minority participants in their specialty clinics than specialist physician investigators in control specialty clinics. Specialty clinic was the unit of randomization. Using continuous quality improvement, the specialist physician investigators and coordinators tailored recruitment approaches to their specialty clinic characteristics and populations. Primary analyses were adjusted for clustering by specialty clinic within parent trial and matching covariates. RECRUIT was implemented in four multi-site clinical trials (parent trials) supported by three National Institutes of Health institutes and included 50 associated specialty clinics from these parent trials. Using current data, we have 88% power or greater to detect a 0.15 or

  3. Random allocation in controlled clinical trials: a review.

    PubMed

    Egbewale, Bolaji Emmanuel

    2014-01-01

    An allocation strategy that allows for chance placement of participants to study groups is crucial to the experimental nature of randomised controlled trials. Following decades of the discovery of randomisation considerable erroneous opinion and misrepresentations of its concept both in principle and practice still exists. In some circles, opinions are also divided on the strength and weaknesses of each of the random allocation strategies. This review provides an update on various random allocation techniques so as to correct existing misconceptions on this all important procedure. This is a review of literatures published in the Pubmed database on concepts of common allocation techniques used in controlled clinical trials. Allocation methods that use; case record number, date of birth, date of presentation, haphazard or alternating assignment are non-random allocation techniques and should not be confused as random methods. Four main random allocation techniques were identified. Minimisation procedure though not fully a random technique, however, proffers solution to the limitations of stratification at balancing for multiple prognostic factors, as the procedure makes treatment groups similar in several important features even in small sample trials. Even though generation of allocation sequence by simple randomisation procedure is easily facilitated, a major drawback of the technique is that treatment groups can by chance end up being dissimilar both in size and composition of prognostic factors. More complex allocation techniques that yield more comparable treatment groups also have certain drawbacks. However, it is important that whichever allocation technique is employed, unpredictability of random assignment should not be compromised.

  4. Testing cardiovascular drug safety and efficacy in randomized trials.

    PubMed

    FitzGerald, Garret A

    2014-03-28

    Randomized trials provide the gold standard evidence on which rests the decision to approve novel therapeutics for clinical use. They are large and expensive and provide average but unbiased estimates of efficacy and risk. Concern has been expressed about how unrepresentative populations and conditions that pertain in randomized trials might be of the real world, including concerns about the homogeneity of the biomedical and adherence characteristics of volunteers entered into such trials, the dose and constancy of drug administration and the mixture of additional medications that are restricted in such trials but might influence outcome in practice. A distinction has been drawn between trials that establish efficacy and those that demonstrate effectiveness, drugs that patients actually consume in the real world for clinical benefit. However, randomized controlled trials remain the gold standard for establishing efficacy and the testing of effectiveness with less rigorous approaches is a secondary, albeit important consideration. Despite this, there is an appreciation that average results may conceal considerable interindividual variation in drug response, leading to a failure to appreciate clinical value or risk in subsets of patients. Thus, attempts are now being made to individualize risk estimates by modulating those derived from large randomized trials with the individual baseline risk estimates based on demographic and biological criteria-the individual Numbers Needed to Treat to obtain a benefit, such as a life saved. Here, I will consider some reasons why large phase 3 trials-by far the most expensive element of drug development-may fail to address the unmet medical needs, which should justify such effort and investment.

  5. What's in placebos: who knows? Analysis of randomized, controlled trials.

    PubMed

    Golomb, Beatrice A; Erickson, Laura C; Koperski, Sabrina; Sack, Deanna; Enkin, Murray; Howick, Jeremy

    2010-10-19

    No regulations govern placebo composition. The composition of placebos can influence trial outcomes and merits reporting. To assess how often investigators specify the composition of placebos in randomized, placebo-controlled trials. 4 English-language general and internal medicine journals with high impact factors. 3 reviewers screened titles and abstracts of the journals to identify randomized, placebo-controlled trials published from January 2008 to December 2009. Reviewers independently abstracted data from the introduction and methods sections of identified articles, recording treatment type (pill, injection, or other) and whether placebo composition was stated. Discrepancies were resolved by consensus. Most studies did not disclose the composition of the study placebo. Disclosure was less common for pills than for injections and other treatments (8.2% vs. 26.7%; P = 0.002). Journals with high impact factors may not be representative. Placebos were seldom described in randomized, controlled trials of pills or capsules. Because the nature of the placebo can influence trial outcomes, placebo formulation should be disclosed in reports of placebo-controlled trials.

  6. Antidepressants as analgesics: a review of randomized controlled trials.

    PubMed Central

    Lynch, M E

    2001-01-01

    This review provides an overview of 59 randomized placebo-controlled trials that examined the analgesic effect of antidepressants. To summarize, there is significant evidence that the tricyclic group of antidepressants is analgesic and that trazodone is not; the data regarding selective serotonin reuptake inhibitors are conflicting. To date, there are no randomized controlled trials examining the potential analgesic action of nefazodone or venlafaxine, but on the basis of initial clinical reports and its structural similarity to other analgesics, venlafaxine shows promise as an analgesic. PMID:11212591

  7. RANDOMIZED CONTROLLED CLINICAL TRIALS IN ORTHOPEDICS: DIFFICULTIES AND LIMITATIONS

    PubMed Central

    Malavolta, Eduardo Angeli; Demange, Marco Kawamura; Gobbi, Riccardo Gomes; Imamura, Marta; Fregni, Felipe

    2015-01-01

    Randomized controlled clinical trials (RCTs) are considered to be the gold standard for evidence-based medicine nowadays, and are important for directing medical practice through consistent scientific observations. Steps such as patient selection, randomization and blinding are fundamental for conducting a RCT, but some additional difficulties are presented in trials that involve surgical procedures, as is common in orthopedics. The aim of this article was to highlight and discuss some difficulties and possible limitations on RCTs within the field of surgery. PMID:27027037

  8. A multiple imputation strategy for sequential multiple assignment randomized trials

    PubMed Central

    Shortreed, Susan M.; Laber, Eric; Stroup, T. Scott; Pineau, Joelle; Murphy, Susan A.

    2014-01-01

    Sequential multiple assignment randomized trials (SMARTs) are increasingly being used to inform clinical and intervention science. In a SMART, each patient is repeatedly randomized over time. Each randomization occurs at a critical decision point in the treatment course. These critical decision points often correspond to milestones in the disease process or other changes in a patient’s health status. Thus, the timing and number of randomizations may vary across patients and depend on evolving patient-specific information. This presents unique challenges when analyzing data from a SMART in the presence of missing data. This paper presents the first comprehensive discussion of missing data issues typical of SMART studies: we describe five specific challenges, and propose a flexible imputation strategy to facilitate valid statistical estimation and inference using incomplete data from a SMART. To illustrate these contributions, we consider data from the Clinical Antipsychotic Trial of Intervention and Effectiveness (CATIE), one of the most well-known SMARTs to date. PMID:24919867

  9. The conduct and principles of randomized clinical trials.

    PubMed

    Klimt, C R

    1981-05-01

    Some of the guiding principles as well as the pitfall of long-term randomized clinical trials are presented. Examples have been chosen from trials in the cardiovascular field. A typical long-term clinical trial is divided into five phases: planning, preparation, recruitment, clinical follow-up and termination, and finally analysis. Administrative, legal, and ethical aspects of a trial are discussed, as well as the cost of clinical trials. Organization patterns are described and some prevalent ones are criticized. Further, practical matters such as recruitment techniques, obtaining informed consent from the patients, determining drug dosage and formulation as well as the problem of interaction with nonstudy drugs are referred to. Adherence testing remains a problem, because of our inability to test for placebo adherence.

  10. Impact of a cancer clinical trials web site on discussions about trial participation: a cluster randomized trial.

    PubMed

    Dear, R F; Barratt, A L; Askie, L M; Butow, P N; McGeechan, K; Crossing, S; Currow, D C; Tattersall, M H N

    2012-07-01

    Cancer patients want access to reliable information about currently recruiting clinical trials. Oncologists and their patients were randomly assigned to access a consumer-friendly cancer clinical trials web site [Australian Cancer Trials (ACT), www.australiancancertrials.gov.au] or to usual care in a cluster randomized controlled trial. The primary outcome, measured from audio recordings of oncologist-patient consultations, was the proportion of patients with whom participation in any clinical trial was discussed. Analysis was by intention-to-treat accounting for clustering and stratification. Thirty medical oncologists and 493 patients were recruited. Overall, 46% of consultations in the intervention group compared with 34% in the control group contained a discussion about clinical trials (P=0.08). The mean consultation length in both groups was 29 min (P=0.69). The proportion consenting to a trial was 10% in both groups (P=0.65). Patients' knowledge about randomized trials was lower in the intervention than the control group (mean score 3.0 versus 3.3, P=0.03) but decisional conflict scores were similar (mean score 42 versus 43, P=0.83). Good communication between patients and physicians is essential. Within this context, a web site such as Australian Cancer Trials may be an important tool to encourage discussion about clinical trial participation.

  11. IS “RESCUE” THERAPY ETHICAL IN RANDOMIZED CONTROLLED TRIALS?

    PubMed Central

    Holubkov, Richard; Michael Dean, J.; Berger, John; Anand, K. J. S.; Carcillo, Joseph; Meert, Kathleen; Zimmerman, Jerry; Newth, Christopher; Harrison, Rick; Willson, Douglas F.; Nicholson, Carol

    2011-01-01

    Objective There is a commonly held belief that randomized, placebo-controlled trials in pediatric critical care should incorporate “rescue” therapy (open-label administration of active drug) when a child’s condition is deteriorating. The ethical, conceptual and analytic challenges related to “rescue” therapy in randomized trials can be misrepresented. Design Narrative review. Methods The ethical basis of “rescue” therapy, the equipoise concept, and intention-to-treat analysis are examined in the setting of a hypothetical randomized trial comparing corticosteroids versus placebo in pediatric septic shock. Findings The perceived need for “rescue” therapy may be partly motivated by the moral imperative to save a child’s life. However, allowing “rescue” therapy in a trial is misconceived and inconsistent with equipoise regarding the efficacy of the study drug. If “rescue” therapy is permitted, intention-to-treat analysis can only compare immediate versus delayed use of the study drug. When “rescue” therapy is beneficial, the observed treatment effect is substantially diminished from true effect of the study drug, leading to increased sample size and thereby placing more children at risk (18 “excess” placebo-arm deaths occur in our hypothetical example). Analysis of a trial incorporating “rescue” therapy cannot definitively assess overall efficacy of the agent, or distinguish beneficial or harmful treatment effects related to timing of drug use. Conclusions While a “rescue” therapy component in a randomized trial may be perceived as ethically desirable, inconsistency of “rescue” therapy with full equipoise may itself raise significant ethical concerns. Increased sample sizes expose more children to the risks of study participation, including death. Researchers should be aware that clinical trials designed with “rescue” therapy cannot definitively determine the beneficial or harmful effects of a treatment per se, and

  12. A clinician's guide for conducting randomized trials in individual patients.

    PubMed Central

    Guyatt, G; Sackett, D; Adachi, J; Roberts, R; Chong, J; Rosenbloom, D; Keller, J

    1988-01-01

    In determining optimal treatment for a patient conventional trials of therapy are susceptible to bias. Large-scale randomized trials can provide only a partial guide and have not been or cannot be carried out for most clinical disorders. However, randomized controlled trials (RCTs) in individual patients (N of 1 RCTs) may in some circumstances provide a solution to this dilemma. In an N of 1 RCT a patient undergoes pairs of treatment periods (one period of each pair with the active drug and one with matched placebo, assigned at random); both the patient and the clinician are blind to allocation, and treatment targets are monitored. N of 1 RCTs are useful for chronic, stable conditions for which the proposed treatment, which has a rapid onset of action and ceases to act soon after it is discontinued, has shown promise in an open trial of therapy. The monitoring of treatment targets usually includes quantitative measurement of the patient's symptoms with the use of simple patient diaries or questionnaires. Pairs of treatment periods are continued until effectiveness is proved or refuted. The cooperation of a pharmacy is required for the preparation of matching placebos and conduct of the trial. Formal statistical analysis may be helpful for interpreting the results. The practical approach presented in this paper allows clinicians to conduct their own N of 1 RCTs. PMID:3409138

  13. Hypnotherapy in radiotherapy patients: A randomized trial

    SciTech Connect

    Stalpers, Lukas J.A. . E-mail: l.stalpers@amc.uva.nl; Costa, Hanna C. da; Merbis, Merijn A.E.; Fortuin, Andries A.; Muller, Martin J.; Dam, Frits van

    2005-02-01

    Purpose: To determine whether hypnotherapy reduces anxiety and improves the quality of life in cancer patients undergoing curative radiotherapy (RT). Methods and materials: After providing written informed consent, 69 patients were randomized between standard curative RT alone (36 controls) and RT plus hypnotherapy (33 patients). Patients in the hypnotherapy group received hypnotherapy at the intake, before RT simulation, before the first RT session, and halfway between the RT course. Anxiety was evaluated by the State-Trait Anxiety Inventory DY-1 form at six points. Quality of life was measured by the Rand Medical Outcomes Study 36-item Health Survey (SF-36) at five points. Additionally, patients answered a questionnaire to evaluate their experience and the possible benefits of this research project. Results: No statistically significant difference was found in anxiety or quality of life between the hypnotherapy and control groups. However, significantly more patients in the hypnotherapy group indicated an improvement in mental (p < 0.05) and overall (p < 0.05) well-being. Conclusion: Hypnotherapy did not reduce anxiety or improve the quality of life in cancer patients undergoing curative RT. The absence of statistically significant differences between the two groups contrasts with the hypnotherapy patients' own sense of mental and overall well-being, which was significantly greater after hypnotherapy. It cannot be excluded that the extra attention by the hypnotherapist was responsible for this beneficial effect in the hypnotherapy group. An attention-only control group would be necessary to control for this effect.

  14. Randomized trial of spacers in asthma.

    PubMed

    Dahiya, Baljit; Mathew, Joseph L; Singh, Meenu

    2007-07-01

    To compare the efficacy of all types of spacers commonly available to children in India. 150 children 5-14 yr of age with persistent asthma presenting with peak expiratory flow (PEF) < 70% of personal best were randomized to receive 200 mg salbutamol through one of five spacers: A) 750 ml spacer with valve, B) 165 ml spacer with valve, C) 250 ml spacer without valve, D) 1000 ml indigenously made spacer without valve and E) 500 ml indigenously made spacer without valve. PEF measurement was repeated 15 minutes later. Children> 8 yr old performed spirometry in addition to PEF. Absolute change and percentage improvement of PEF and FEV1 were compared among the groups. Subjects in all groups had comparable baseline demographic characteristics and PEF. All showed significant improvement in PEF and FEV1 over baseline values. The change in PEF and percentage improvement were comparable among all five groups (p=0.780 and p=0.955 respectively). Likewise change in FEV1 and percentage improvement were also comparable. The five groups showed no difference in efficacy, irrespective of severity of baseline airway obstruction. The five spacers were equally efficacious for the delivery of bronchodilator in children with moderate persistent asthma presenting with airway obstruction.

  15. A Randomized Controlled Trial of Two Online Mathematics Curricula

    ERIC Educational Resources Information Center

    Wang, Haiwen; Woodworth, Katrina

    2011-01-01

    This study applies a randomized controlled trial to examine the effects of supplemental instruction using two online mathematics curricula--DreamBox and Reasoning Mind. It is an independent evaluation intended to generate unbiased results that will help inform the ongoing development of a charter school network's hybrid instructional model, which…

  16. In School Settings, Are All RCTs (Randomized Control Trials) Exploratory?

    ERIC Educational Resources Information Center

    Newman, Denis; Jaciw, Andrew P.

    2012-01-01

    The motivation for this paper is the authors' recent work on several randomized control trials in which they found the primary result, which averaged across subgroups or sites, to be moderated by demographic or site characteristics. They are led to examine a distinction that the Institute of Education Sciences (IES) makes between "confirmatory"…

  17. Can the Randomized Controlled Trial Literature Generalize to Nonrandomized Patients?

    ERIC Educational Resources Information Center

    Stirman, Shannon Wiltsey; DeRubeis, Robert J.; Crits-Christoph, Paul; Rothman, Allison

    2005-01-01

    To determine the extent to which published randomized controlled trials (RCTs) of psychotherapy can be generalized to a sample of outpatients, the authors matched information obtained from charts of patients who had been screened out of RCTs to inclusion and exclusion criteria from published RCT studies. Most of the patients in the sample who had…

  18. Asthma Self-Management Model: Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Olivera, Carolina M. X.; Vianna, Elcio Oliveira; Bonizio, Roni C.; de Menezes, Marcelo B.; Ferraz, Erica; Cetlin, Andrea A.; Valdevite, Laura M.; Almeida, Gustavo A.; Araujo, Ana S.; Simoneti, Christian S.; de Freitas, Amanda; Lizzi, Elisangela A.; Borges, Marcos C.; de Freitas, Osvaldo

    2016-01-01

    Information for patients provided by the pharmacist is reflected in adhesion to treatment, clinical results and patient quality of life. The objective of this study was to assess an asthma self-management model for rational medicine use. This was a randomized controlled trial with 60 asthmatic patients assigned to attend five modules presented by…

  19. Randomization Methods in Emergency Setting Trials: A Descriptive Review

    ERIC Educational Resources Information Center

    Corbett, Mark Stephen; Moe-Byrne, Thirimon; Oddie, Sam; McGuire, William

    2016-01-01

    Background: Quasi-randomization might expedite recruitment into trials in emergency care settings but may also introduce selection bias. Methods: We searched the Cochrane Library and other databases for systematic reviews of interventions in emergency medicine or urgent care settings. We assessed selection bias (baseline imbalances) in prognostic…

  20. 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…

  1. Randomized Trial of Drug Abuse Treatment-Linkage Strategies

    ERIC Educational Resources Information Center

    Sorenson, James L.; Masson, Carmen L.; Delucchi, Kevin; Sporer, Karl; Barnett, Paul G.; Mitsuishi, Fumi; Lin, Christine; Song, Yong; Chen, TeChieh; Hall, Sharon M.

    2005-01-01

    A clinical trial contrasted 2 interventions designed to link opioid-dependent hospital patients to drug abuse treatment. The 126 out-of-treatment participants were randomly assigned to (a) case management, (b) voucher for free methadone maintenance treatment (MMT), (c) case management plus voucher, or (d) usual care. Services were provided for 6…

  2. Using Randomized Controlled Trials to Evaluate Interventions for Releasing Prisoners

    ERIC Educational Resources Information Center

    Pettus-Davis, Carrie; Howard, Matthew Owen; Dunnigan, Allison; Scheyett, Anna M.; Roberts-Lewis, Amelia

    2016-01-01

    Randomized controlled trials (RCTs) are rarely used to evaluate social and behavioral interventions designed for releasing prisoners. Objective: We use a pilot RCT of a social support intervention (Support Matters) as a case example to discuss obstacles and strategies for conducting RCT intervention evaluations that span prison and community…

  3. 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…

  4. Can the Randomized Controlled Trial Literature Generalize to Nonrandomized Patients?

    ERIC Educational Resources Information Center

    Stirman, Shannon Wiltsey; DeRubeis, Robert J.; Crits-Christoph, Paul; Rothman, Allison

    2005-01-01

    To determine the extent to which published randomized controlled trials (RCTs) of psychotherapy can be generalized to a sample of outpatients, the authors matched information obtained from charts of patients who had been screened out of RCTs to inclusion and exclusion criteria from published RCT studies. Most of the patients in the sample who had…

  5. In School Settings, Are All RCTs (Randomized Control Trials) Exploratory?

    ERIC Educational Resources Information Center

    Newman, Denis; Jaciw, Andrew P.

    2012-01-01

    The motivation for this paper is the authors' recent work on several randomized control trials in which they found the primary result, which averaged across subgroups or sites, to be moderated by demographic or site characteristics. They are led to examine a distinction that the Institute of Education Sciences (IES) makes between "confirmatory"…

  6. Asthma Self-Management Model: Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Olivera, Carolina M. X.; Vianna, Elcio Oliveira; Bonizio, Roni C.; de Menezes, Marcelo B.; Ferraz, Erica; Cetlin, Andrea A.; Valdevite, Laura M.; Almeida, Gustavo A.; Araujo, Ana S.; Simoneti, Christian S.; de Freitas, Amanda; Lizzi, Elisangela A.; Borges, Marcos C.; de Freitas, Osvaldo

    2016-01-01

    Information for patients provided by the pharmacist is reflected in adhesion to treatment, clinical results and patient quality of life. The objective of this study was to assess an asthma self-management model for rational medicine use. This was a randomized controlled trial with 60 asthmatic patients assigned to attend five modules presented by…

  7. Affectionate Writing Reduces Total Cholesterol: Two Randomized, Controlled Trials

    ERIC Educational Resources Information Center

    Floyd, Kory; Mikkelson, Alan C.; Hesse, Colin; Pauley, Perry M.

    2007-01-01

    In two 5-week trials, healthy college students were randomly assigned either to experimental or control groups. Participants in the experimental groups wrote about their affection for significant friends, relatives, and/or romantic partners for 20 minutes on three separate occasions; on the same schedule, those in the control groups wrote about…

  8. Randomization Methods in Emergency Setting Trials: A Descriptive Review

    ERIC Educational Resources Information Center

    Corbett, Mark Stephen; Moe-Byrne, Thirimon; Oddie, Sam; McGuire, William

    2016-01-01

    Background: Quasi-randomization might expedite recruitment into trials in emergency care settings but may also introduce selection bias. Methods: We searched the Cochrane Library and other databases for systematic reviews of interventions in emergency medicine or urgent care settings. We assessed selection bias (baseline imbalances) in prognostic…

  9. A Multisite Cluster Randomized Field Trial of Open Court Reading

    ERIC Educational Resources Information Center

    Borman, Geoffrey D.; Dowling, N. Maritza; Schneck, Carrie

    2008-01-01

    In this article, the authors report achievement outcomes of a multisite cluster randomized field trial of Open Court Reading 2005 (OCR), a K-6 literacy curriculum published by SRA/McGraw-Hill. The participants are 49 first-grade through fifth-grade classrooms from predominantly minority and poor contexts across the nation. Blocking by grade level…

  10. Using Randomized Controlled Trials to Evaluate Interventions for Releasing Prisoners

    ERIC Educational Resources Information Center

    Pettus-Davis, Carrie; Howard, Matthew Owen; Dunnigan, Allison; Scheyett, Anna M.; Roberts-Lewis, Amelia

    2016-01-01

    Randomized controlled trials (RCTs) are rarely used to evaluate social and behavioral interventions designed for releasing prisoners. Objective: We use a pilot RCT of a social support intervention (Support Matters) as a case example to discuss obstacles and strategies for conducting RCT intervention evaluations that span prison and community…

  11. Randomized Trial of Drug Abuse Treatment-Linkage Strategies

    ERIC Educational Resources Information Center

    Sorenson, James L.; Masson, Carmen L.; Delucchi, Kevin; Sporer, Karl; Barnett, Paul G.; Mitsuishi, Fumi; Lin, Christine; Song, Yong; Chen, TeChieh; Hall, Sharon M.

    2005-01-01

    A clinical trial contrasted 2 interventions designed to link opioid-dependent hospital patients to drug abuse treatment. The 126 out-of-treatment participants were randomly assigned to (a) case management, (b) voucher for free methadone maintenance treatment (MMT), (c) case management plus voucher, or (d) usual care. Services were provided for 6…

  12. Randomized, Controlled Trial of CBT Training for PTSD Providers

    DTIC Science & Technology

    2015-10-01

    902-909. Shapiro, F. (2001). Eye movement desensitization and reprocessing (EMDR): Basic principles, protocols, and procedures (2nd ed.) (2nd ed...A randomized clinical trial of eye movement desensitization and reprocessing (EMDR), fluoxetine, and pill placebo in the treatment of

  13. Affectionate Writing Reduces Total Cholesterol: Two Randomized, Controlled Trials

    ERIC Educational Resources Information Center

    Floyd, Kory; Mikkelson, Alan C.; Hesse, Colin; Pauley, Perry M.

    2007-01-01

    In two 5-week trials, healthy college students were randomly assigned either to experimental or control groups. Participants in the experimental groups wrote about their affection for significant friends, relatives, and/or romantic partners for 20 minutes on three separate occasions; on the same schedule, those in the control groups wrote about…

  14. Promoting Healthy Weight with "Stability Skills First": A Randomized Trial

    ERIC Educational Resources Information Center

    Kiernan, Michaela; Brown, Susan D.; Schoffman, Danielle E.; Lee, Katherine; King, Abby C.; Taylor, C. Barr; Schleicher, Nina C.; Perri, Michael G.

    2013-01-01

    Objective: Although behavioral weight-loss interventions produce short-term weight loss, long-term maintenance remains elusive. This randomized trial examined whether learning a novel set of "stability skills" before losing weight improved long-term weight management. Stability skills were designed to optimize individuals' current…

  15. Randomized, Controlled Trial of CBT Training for PTSD Providers

    DTIC Science & Technology

    2013-10-01

    and Therapy, 47, 902-909. Shapiro, F. (2001). Eye movement desensitization and reprocessing ( EMDR ): Basic principles...Hopper, E. K., Korn, D. L., & Simpson, W. B. (2007). A randomized clinical trial of eye movement desensitization and reprocessing ( EMDR ), fluoxetine...Josef Ruzek, Ph.D. CONTRACTING ORGANIZATION: Palo Alto Institute for Research and Education Palo Alto, CA 94304 REPORT

  16. Randomized, Controlled Trial of CBT Training for PTSD Providers

    DTIC Science & Technology

    2013-10-01

    and Therapy, 47, 902-909. Shapiro, F. (2001). Eye movement desensitization and reprocessing ( EMDR ): Basic principles, protocols, and procedures...Simpson, W. B. (2007). A randomized clinical trial of eye movement desensitization and reprocessing ( EMDR ), fluoxetine, and pill placebo in the...21702 DISTRIBUTION STATEMENT: Approved for Public Release; Distribution Unlimited The views, opinions

  17. Promoting Healthy Weight with "Stability Skills First": A Randomized Trial

    ERIC Educational Resources Information Center

    Kiernan, Michaela; Brown, Susan D.; Schoffman, Danielle E.; Lee, Katherine; King, Abby C.; Taylor, C. Barr; Schleicher, Nina C.; Perri, Michael G.

    2013-01-01

    Objective: Although behavioral weight-loss interventions produce short-term weight loss, long-term maintenance remains elusive. This randomized trial examined whether learning a novel set of "stability skills" before losing weight improved long-term weight management. Stability skills were designed to optimize individuals' current…

  18. Review of Randomized Controlled Trials of Massage in Preterm Infants.

    PubMed

    Niemi, Anna-Kaisa

    2017-04-03

    Preterm birth affects about 10% of infants born in the United States. Massage therapy is being used in some neonatal intensive care units for its potential beneficial effects on preterm infants. This article reviews published randomized controlled trials on the effects of massage in preterm infants. Most studies evaluating the effect of massage in weight gain in premature infants suggest a positive effect on weight gain. Increase in vagal tone has been reported in infants who receive massage and has been suggested as a possible mechanism for improved weight gain. More studies are needed on the underlying mechanisms of the effects of massage therapy on weight gain in preterm infants. While some trials suggest improvements in developmental scores, decreased stress behavior, positive effects on immune system, improved pain tolerance and earlier discharge from the hospital, the number of such studies is small and further evidence is needed. Further studies, including randomized controlled trials, are needed on the effects of massage in preterm infants.

  19. A Randomized Trial of Text2Quit

    PubMed Central

    Abroms, Lorien C.; Boal, Ashley L.; Simmens, Samuel J.; Mendel, Judith A.; Windsor, Richard A.

    2014-01-01

    Background Text messaging programs on mobile phones have shown some promise in helping people quit smoking. Text2Quit is an automated, personalized, interactive mobile health program that sends text messages to offer advice, support, and reminders about quitting smoking. Purpose To evaluate the effect of Text2Quit on biochemically confirmed repeated point prevalence abstinence in the context of an RCT conducted in the U.S. Methods Participants (n=503) were recruited on the Internet and randomized to receive Text2Quit or self-help material. Between 2011 and 2013, participants were surveyed at baseline and at 1, 3, and 6 months post-enrollment to assess smoking status. Saliva was collected from participants who reported not smoking in the past 7 days at the 6-month follow-up. An intent to treat analysis was used, and those lost to follow-up were categorized as smokers. All analyses were completed in 2013. Results Biochemically confirmed repeated point prevalence abstinence favored the intervention group, with 11.1% abstinent compared to 5.0% of the control group (relative risk [RR]=2.22, CI=1.16, 4.26, p<0.05). Similarly, self reported repeated point prevalence abstinence was higher in the intervention group (19.9%) than in the control group (10.0%) (p<0.01). Effects were found to be uniform across the analyzed demographic subgroups, although suggestive of a larger effect for non-whites than whites. Conclusions These results provide initial support for the relative efficacy of the Text2Quit program. PMID:24913220

  20. Multilevel analysis of group-randomized trials with binary outcomes.

    PubMed

    Kim, Hae-Young; Preisser, John S; Rozier, R Gary; Valiyaparambil, Jayasanker V

    2006-08-01

    Many dental studies have assessed the effectiveness of community- or group-based interventions such as community water fluoridation. These cluster trials, of which group-randomized trials (GRTs) are one type, have design and analysis considerations not found in studies with randomization of treatments to individuals (randomized controlled trials, RCTs). The purpose of this paper is to review analytic methods used for the analysis of binary outcomes from cluster trials and to illustrate these concepts and analytical methods using a school-based GRT. We examine characteristics of GRTs including intra-class correlation (ICC), their most distinctive feature, and review analytical methods for GRTs including group-level analysis, adjusted chi-square test and multivariable analysis (mixed effect models and generalized estimating equations) for correlated binary data. We consider two- and three-level modeling of data from a cross-sectional cluster design. We apply the concepts reviewed using a GRT designed to determine the effect of incentives on response rates in a school-based dental study. We compare the results of analyses using methods for correlated binary data with those from traditional methods that do not account for ICC. Application of traditional analytic methods to the dental GRT used as an example for this paper led to a substantial overstatement of the effectiveness of the intervention. Ignoring the ICC among members of the same group in the analysis of public health intervention studies can lead to erroneous conclusions where groups are the unit of assignment. Special consideration is needed in the analysis of data from these cluster trials. Randomization of treatments to groups also should receive more consideration in the design of cluster trials in dental public health.

  1. Reporting of statistically significant results at ClinicalTrials.gov for completed superiority randomized controlled trials.

    PubMed

    Dechartres, Agnes; Bond, Elizabeth G; Scheer, Jordan; Riveros, Carolina; Atal, Ignacio; Ravaud, Philippe

    2016-11-30

    Publication bias and other reporting bias have been well documented for journal articles, but no study has evaluated the nature of results posted at ClinicalTrials.gov. We aimed to assess how many randomized controlled trials (RCTs) with results posted at ClinicalTrials.gov report statistically significant results and whether the proportion of trials with significant results differs when no treatment effect estimate or p-value is posted. We searched ClinicalTrials.gov in June 2015 for all studies with results posted. We included completed RCTs with a superiority hypothesis and considered results for the first primary outcome with results posted. For each trial, we assessed whether a treatment effect estimate and/or p-value was reported at ClinicalTrials.gov and if yes, whether results were statistically significant. If no treatment effect estimate or p-value was reported, we calculated the treatment effect and corresponding p-value using results per arm posted at ClinicalTrials.gov when sufficient data were reported. From the 17,536 studies with results posted at ClinicalTrials.gov, we identified 2823 completed phase 3 or 4 randomized trials with a superiority hypothesis. Of these, 1400 (50%) reported a treatment effect estimate and/or p-value. Results were statistically significant for 844 trials (60%), with a median p-value of 0.01 (Q1-Q3: 0.001-0.26). For the 1423 trials with no treatment effect estimate or p-value posted, we could calculate the treatment effect and corresponding p-value using results reported per arm for 929 (65%). For 494 trials (35%), p-values could not be calculated mainly because of insufficient reporting, censored data, or repeated measurements over time. For the 929 trials we could calculate p-values, we found statistically significant results for 342 (37%), with a median p-value of 0.19 (Q1-Q3: 0.005-0.59). Half of the trials with results posted at ClinicalTrials.gov reported a treatment effect estimate and/or p-value, with significant

  2. Project Management of Randomized Clinical Trials: A Narrative Review

    PubMed Central

    Goodarzynejad, Hamidreza; Babamahmoodi, Abdolreza

    2015-01-01

    Context: A well-structured protocol for a clinical trial may be able to answer clinical questions, but it cannot be deemed enough to ensure success in the face of incompetent management of time as well as human and economic resources. To address this problem, in this article, we present our literature review on evidence as to how a good knowledge of proper management among researchers can enhance the likelihood of the success of clinical trial projects. Evidence Acquisition: Using multiple search strategies, we conducted a literature review on published studies in the English language from 2002 to 2012 by searching the Cochrane Database of Systematic Reviews, MEDLINE, Google Scholar, and EMBASE. Results: Our review suggests that a successful trial requires a work plan or work scope as well as a timeline. The trial manager should subsequently manage the study in accordance with the plan and the timeline. Many research units have called for a clinical project manager with scientific background and regulatory skills to effect coordination among various aspects of a clinical trial. Conclusions: Project management may benefit both the managerial and scientific aspects of medical projects and reduce fund waste. However, little has been written to date on project management in the context of clinical research. The suggestions represent the views of the individual authors. To provide a high level of evidence in this regard, we recommend that a randomized controlled trial be performed to compare trial projects progressed with and without the use of project management. PMID:26430517

  3. Global randomized trials: the promise of India and China.

    PubMed

    Perkovic, Vlado; Patil, Vinodvenkatesh; Wei, Liu; Lv, Jicheng; Petersen, Marisa; Patel, Anushka

    2012-07-18

    Although modern clinical trials are traditionally conducted in Western countries, currently there is a shift to involve developing countries, particularly China and India. For these trials, the large population size of India and China means that substantial numbers of individuals affected by rare diseases may be found, increasing the likelihood of successfully completing enrollment in a clinical trial. Furthermore, the increasing involvement of Asian countries in global clinical trials is likely to lead to greater appreciation of the value of evidence-based treatment decisions in the region. These sites are more cost-effective, although this advantage is being eroded over time. Asian participants in clinical trials are also typically more likely to complete study follow-up and procedures, and to adhere to their randomized treatment allocation than individuals from Western countries. Challenges include relevance of the proposed trial to the region, capacity limitations because of undeveloped training, and ensuring research implementation quality and different intellectual property practices. There are specific challenges to conducting clinical trials in India, such as the status of ethics committees, health insurance and coverage for participants, and variability in languages and record-keeping. Challenges in both countries are substantial but are able to be managed with appropriate planning.

  4. A method of extracting the number of trial participants from abstracts describing randomized controlled trials.

    PubMed

    Hansen, Marie J; Rasmussen, Nana Ø; Chung, Grace

    2008-01-01

    We have developed a method for extracting the number of trial participants from abstracts describing randomized controlled trials (RCTs); the number of trial participants may be an indication of the reliability of the trial. The method depends on statistical natural language processing. The number of interest was determined by a binary supervised classification based on a support vector machine algorithm. The method was trialled on 223 abstracts in which the number of trial participants was identified manually to act as a gold standard. Automatic extraction resulted in 2 false-positive and 19 false-negative classifications. The algorithm was capable of extracting the number of trial participants with an accuracy of 97% and an F-measure of 0.84. The algorithm may improve the selection of relevant articles in regard to question-answering, and hence may assist in decision-making.

  5. An Overview of Randomization and Minimization Programs for Randomized Clinical Trials

    PubMed Central

    Saghaei, Mahmoud

    2011-01-01

    Randomization is an essential component of sound clinical trials, which prevents selection biases and helps in blinding the allocations. Randomization is a process by which subsequent subjects are enrolled into trial groups only by chance, which essentially eliminates selection biases. A serious consequence of randomization is severe imbalance among the treatment groups with respect to some prognostic factors, which invalidate the trial results or necessitate complex and usually unreliable secondary analysis to eradicate the source of imbalances. Minimization on the other hand tends to allocate in such a way as to minimize the differences among groups, with respect to prognostic factors. Pure minimization is therefore completely deterministic, that is, one can predict the allocation of the next subject by knowing the factor levels of a previously enrolled subject and having the properties of the next subject. To eliminate the predictability of randomization, it is necessary to include some elements of randomness in the minimization algorithms. In this article brief descriptions of randomization and minimization are presented followed by introducing selected randomization and minimization programs. PMID:22606659

  6. Central Retinal Enrichment Supplementation Trials (CREST): Design and Methodology of the CREST Randomized Controlled Trials

    PubMed Central

    Beatty, Stephen; Stack, Jim; Dennison, Jessica; O’Regan, Sarah; Meagher, Katherine A.; Peto, Tunde; Nolan, John

    2014-01-01

    Purpose The Central Retinal Enrichment Supplementation Trials (CREST) aim to investigate the potential impact of macular pigment (MP) enrichment, following supplementation with a formulation containing 10 mg lutein (L), 2 mg zeaxanthin (Z) and 10 mg meso-zeaxanthin (MZ), on visual function in normal subjects (Trial 1) and in subjects with early age-related macular degeneration (AMD; Trial 2). Methods CREST is a single center, double-blind, randomized clinical trial. Trial 1 (12-month follow-up) subjects are randomly assigned to a formulation containing 10 mg L, 10 mg MZ and 2 mg Z (n = 60) or placebo (n = 60). Trial 2 (24-month follow-up) subjects are randomly assigned to a formulation containing 10 mg L, 10 mg MZ, 2 mg Z plus 500 mg vitamin C, 400 IU vitamin E, 25 mg zinc and 2 mg copper (Intervention A; n = 75) or 10 mg L and 2 mg Z plus 500 mg vitamin C, 400 IU vitamin E, 25 mg zinc and 2 mg copper (Intervention B; n = 75). Contrast sensitivity (CS) at 6 cycles per degree represents the primary outcome measure in each trial. Secondary outcomes include: CS at other spatial frequencies, MP, best-corrected visual acuity, glare disability, photostress recovery, light scatter, cognitive function, foveal architecture, serum carotenoid concentrations, and subjective visual function. For Trial 2, AMD morphology, reading speed and reading acuity are also being recorded. Conclusions CREST is the first study to investigate the impact of supplementation with all three macular carotenoids in the context of a large, double-blind, randomized clinical trial. PMID:24621122

  7. Randomized controlled trials of malaria intervention trials in Africa, 1948 to 2007: a descriptive analysis.

    PubMed

    Lutje, Vittoria; Gerritsen, Annette; Siegfried, Nandi

    2011-03-15

    Nine out of ten deaths from malaria occur in sub-Saharan Africa. Various control measures have achieved some progress in the control of the disease, but malaria is still a major public health problem in Africa. Randomized controlled trials (RCTs) are universally considered the best study type to rigorously assess whether an intervention is effective. The study reported here provides a descriptive analysis of RCTs reporting interventions for the prevention and treatment of malaria conducted in Africa, with the aim of providing detailed information on their main clinical and methodological characteristics, that could be used by researchers and policy makers to help plan future research. Systematic searches for malaria RCTs were conducted using electronic databases (Medline, Embase, the Cochrane Library), and an African geographic search filter to identify RCTs conducted in Africa was applied. Results were exported to the statistical package STATA 8 to obtain a random sample from the overall data set. Final analysis of trial characteristics was done in a double blinded fashion by two authors using a standardized data extraction form. A random sample of 92 confirmed RCTs (from a total of 943 reports obtained between 1948 and 2007) was prepared. Most trials investigated drug treatment in children with uncomplicated malaria. Few trials reported on treatment of severe malaria or on interventions in pregnant women. Most trials were of medium size (100-500 participants), individually randomized and based in a single centre. Reporting of trial quality was variable. Although three-quarter of trials provided information on participants' informed consent and ethics approval, more details are needed. The majority of malaria RCT conducted in Africa report on drug treatment and prevention in children; there is need for more research done in pregnant women. Sources of funding, informed consent and trial quality were often poorly reported. Overall, clearer reporting of trials is

  8. Randomized controlled trials of malaria intervention trials in Africa, 1948 to 2007: a descriptive analysis

    PubMed Central

    2011-01-01

    Background Nine out of ten deaths from malaria occur in sub-Saharan Africa. Various control measures have achieved some progress in the control of the disease, but malaria is still a major public health problem in Africa. Randomized controlled trials (RCTs) are universally considered the best study type to rigorously assess whether an intervention is effective. The study reported here provides a descriptive analysis of RCTs reporting interventions for the prevention and treatment of malaria conducted in Africa, with the aim of providing detailed information on their main clinical and methodological characteristics, that could be used by researchers and policy makers to help plan future research. Methods Systematic searches for malaria RCTs were conducted using electronic databases (Medline, Embase, the Cochrane Library), and an African geographic search filter to identify RCTs conducted in Africa was applied. Results were exported to the statistical package STATA 8 to obtain a random sample from the overall data set. Final analysis of trial characteristics was done in a double blinded fashion by two authors using a standardized data extraction form. Results A random sample of 92 confirmed RCTs (from a total of 943 reports obtained between 1948 and 2007) was prepared. Most trials investigated drug treatment in children with uncomplicated malaria. Few trials reported on treatment of severe malaria or on interventions in pregnant women. Most trials were of medium size (100-500 participants), individually randomized and based in a single centre. Reporting of trial quality was variable. Although three-quarter of trials provided information on participants' informed consent and ethics approval, more details are needed. Conclusions The majority of malaria RCT conducted in Africa report on drug treatment and prevention in children; there is need for more research done in pregnant women. Sources of funding, informed consent and trial quality were often poorly reported

  9. Central Retinal Enrichment Supplementation Trials (CREST): design and methodology of the CREST randomized controlled trials.

    PubMed

    Akuffo, Kwadwo Owusu; Beatty, Stephen; Stack, Jim; Dennison, Jessica; O'Regan, Sarah; Meagher, Katherine A; Peto, Tunde; Nolan, John

    2014-04-01

    The Central Retinal Enrichment Supplementation Trials (CREST) aim to investigate the potential impact of macular pigment (MP) enrichment, following supplementation with a formulation containing 10 mg lutein (L), 2 mg zeaxanthin (Z) and 10 mg meso-zeaxanthin (MZ), on visual function in normal subjects (Trial 1) and in subjects with early age-related macular degeneration (AMD; Trial 2). CREST is a single center, double-blind, randomized clinical trial. Trial 1 (12-month follow-up) subjects are randomly assigned to a formulation containing 10 mg L, 10 mg MZ and 2 mg Z (n = 60) or placebo (n = 60). Trial 2 (24-month follow-up) subjects are randomly assigned to a formulation containing 10 mg L, 10 mg MZ, 2 mg Z plus 500 mg vitamin C, 400 IU vitamin E, 25 mg zinc and 2 mg copper (Intervention A; n = 75) or 10 mg L and 2 mg Z plus 500 mg vitamin C, 400 IU vitamin E, 25 mg zinc and 2 mg copper (Intervention B; n = 75). Contrast sensitivity (CS) at 6 cycles per degree represents the primary outcome measure in each trial. Secondary outcomes include: CS at other spatial frequencies, MP, best-corrected visual acuity, glare disability, photostress recovery, light scatter, cognitive function, foveal architecture, serum carotenoid concentrations, and subjective visual function. For Trial 2, AMD morphology, reading speed and reading acuity are also being recorded. CREST is the first study to investigate the impact of supplementation with all three macular carotenoids in the context of a large, double-blind, randomized clinical trial.

  10. Leveraging prognostic baseline variables to gain precision in randomized trials.

    PubMed

    Colantuoni, Elizabeth; Rosenblum, Michael

    2015-08-15

    We focus on estimating the average treatment effect in a randomized trial. If baseline variables are correlated with the outcome, then appropriately adjusting for these variables can improve precision. An example is the analysis of covariance (ANCOVA) estimator, which applies when the outcome is continuous, the quantity of interest is the difference in mean outcomes comparing treatment versus control, and a linear model with only main effects is used. ANCOVA is guaranteed to be at least as precise as the standard unadjusted estimator, asymptotically, under no parametric model assumptions and also is locally semiparametric efficient. Recently, several estimators have been developed that extend these desirable properties to more general settings that allow any real-valued outcome (e.g., binary or count), contrasts other than the difference in mean outcomes (such as the relative risk), and estimators based on a large class of generalized linear models (including logistic regression). To the best of our knowledge, we give the first simulation study in the context of randomized trials that compares these estimators. Furthermore, our simulations are not based on parametric models; instead, our simulations are based on resampling data from completed randomized trials in stroke and HIV in order to assess estimator performance in realistic scenarios. We provide practical guidance on when these estimators are likely to provide substantial precision gains and describe a quick assessment method that allows clinical investigators to determine whether these estimators could be useful in their specific trial contexts.

  11. Leveraging prognostic baseline variables to gain precision in randomized trials

    PubMed Central

    Colantuoni, Elizabeth; Rosenblum, Michael

    2015-01-01

    We focus on estimating the average treatment effect in a randomized trial. If baseline variables are correlated with the outcome, then appropriately adjusting for these variables can improve precision. An example is the analysis of covariance (ANCOVA) estimator, which applies when the outcome is continuous, the quantity of interest is the difference in mean outcomes comparing treatment versus control, and a linear model with only main effects is used. ANCOVA is guaranteed to be at least as precise as the standard unadjusted estimator, asymptotically, under no parametric model assumptions and also is locally semiparametric efficient. Recently, several estimators have been developed that extend these desirable properties to more general settings that allow any real-valued outcome (e.g., binary or count), contrasts other than the difference in mean outcomes (such as the relative risk), and estimators based on a large class of generalized linear models (including logistic regression). To the best of our knowledge, we give the first simulation study in the context of randomized trials that compares these estimators. Furthermore, our simulations are not based on parametric models; instead, our simulations are based on resampling data from completed randomized trials in stroke and HIV in order to assess estimator performance in realistic scenarios. We provide practical guidance on when these estimators are likely to provide substantial precision gains and describe a quick assessment method that allows clinical investigators to determine whether these estimators could be useful in their specific trial contexts. PMID:25872751

  12. 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.

  13. Randomization in clinical trials in orthodontics: its significance in research design and methods to achieve it.

    PubMed

    Pandis, Nikolaos; Polychronopoulou, Argy; Eliades, Theodore

    2011-12-01

    Randomization is a key step in reducing selection bias during the treatment allocation phase in randomized clinical trials. The process of randomization follows specific steps, which include generation of the randomization list, allocation concealment, and implementation of randomization. The phenomenon in the dental and orthodontic literature of characterizing treatment allocation as random is frequent; however, often the randomization procedures followed are not appropriate. Randomization methods assign, at random, treatment to the trial arms without foreknowledge of allocation by either the participants or the investigators thus reducing selection bias. Randomization entails generation of random allocation, allocation concealment, and the actual methodology of implementing treatment allocation randomly and unpredictably. Most popular randomization methods include some form of restricted and/or stratified randomization. This article introduces the reasons, which make randomization an integral part of solid clinical trial methodology, and presents the main randomization schemes applicable to clinical trials in orthodontics.

  14. Randomized Phase II Trial of Sulindac for Lung Cancer Chemoprevention

    PubMed Central

    Limburg, Paul J.; Mandrekar, Sumithra J.; Aubry, Marie Christine; Ziegler, Katie L. Allen; Zhang, Jun; Yi, Joanne E.; Henry, Michael; Tazelaar, Henry D.; Lam, Stephen; McWilliams, Annette; Midthun, David E.; Edell, Eric S.; Rickman, Otis B.; Mazzone, Peter; Tockman, Melvyn; Beamis, John F.; Lamb, Carla; Simoff, Michael; Loprinzi, Charles; Szabo, Eva; Jett, James

    2012-01-01

    Introduction Sulindac represents a promising candidate agent for lung cancer chemoprevention, but clinical trial data have not been previously reported. We conducted a randomized, phase II chemoprevention trial involving current or former cigarette smokers (≥ 30 pack-years) utilizing the multi-center, inter-disciplinary infrastructure of the Cancer Prevention Network (CPN). Methods At least 1 bronchial dysplastic lesion identified by fluorescence bronchoscopy was required for randomization. Intervention assignments were sulindac 150 mg bid or an identical placebo bid for six months. Trial endpoints included changes in histologic grade of dysplasia (per-participant as primary endpoint and per lesion as secondary endpoint), number of dysplastic lesions (per-participant), and Ki67 labeling index. Results Slower than anticipated recruitment led to trial closure after randomizing participants (n = 31 and n = 30 in the sulindac and placebo arms, respectively). Pre- and post-intervention fluorescence bronchoscopy data were available for 53/61 (87%) randomized, eligible participants. The median (range) of dysplastic lesions at baseline was 2 (1-12) in the sulindac arm and 2 (1-7) in the placebo arm. Change in dysplasia was categorized as regression:stable:progression for 15:3:8 (58%:12%:31%) subjects in the sulindac arm and 15:2:10 (56%:7%:37%) subjects in the placebo arm; these distributions were not statistically different (p=0.85). Median Ki67 expression (% cells stained positive) was significantly reduced in both the placebo (30 versus 5; p = 0.0005) and sulindac (30 versus 10; p = 0.0003) arms, but the difference between arms was not statistically significant (p = 0.92). Conclusions Data from this multi-center, phase II squamous cell lung cancer chemoprevention trial do not demonstrate sufficient benefits from sulindac 150 mg bid for 6 months to warrant additional phase III testing. Investigation of pathway-focused agents is necessary for lung cancer chemoprevention

  15. Randomized Controlled Trials of Add-On Antidepressants in Schizophrenia.

    PubMed

    Terevnikov, Viacheslav; Joffe, Grigori; Stenberg, Jan-Henry

    2015-05-19

    Despite adequate treatment with antipsychotics, a substantial number of patients with schizophrenia demonstrate only suboptimal clinical outcome. To overcome this challenge, various psychopharmacological combination strategies have been used, including antidepressants added to antipsychotics. To analyze the efficacy of add-on antidepressants for the treatment of negative, positive, cognitive, depressive, and antipsychotic-induced extrapyramidal symptoms in schizophrenia, published randomized controlled trials assessing the efficacy of adjunctive antidepressants in schizophrenia were reviewed using the following parameters: baseline clinical characteristics and number of patients, their on-going antipsychotic treatment, dosage of the add-on antidepressants, duration of the trial, efficacy measures, and outcomes. There were 36 randomized controlled trials reported in 41 journal publications (n=1582). The antidepressants used were the selective serotonin reuptake inhibitors, duloxetine, imipramine, mianserin, mirtazapine, nefazodone, reboxetin, trazodone, and bupropion. Mirtazapine and mianserin showed somewhat consistent efficacy for negative symptoms and both seemed to enhance neurocognition. Trazodone and nefazodone appeared to improve the antipsychotics-induced extrapyramidal symptoms. Imipramine and duloxetine tended to improve depressive symptoms. No clear evidence supporting selective serotonin reuptake inhibitors' efficacy on any clinical domain of schizophrenia was found. Add-on antidepressants did not worsen psychosis. Despite a substantial number of randomized controlled trials, the overall efficacy of add-on antidepressants in schizophrenia remains uncertain mainly due to methodological issues. Some differences in efficacy on several schizophrenia domains seem, however, to exist and to vary by the antidepressant subgroups--plausibly due to differences in the mechanisms of action. Antidepressants may not worsen the course of psychosis. Better designed

  16. Randomized Controlled Trials of Add-On Antidepressants in Schizophrenia

    PubMed Central

    Joffe, Grigori; Stenberg, Jan-Henry

    2015-01-01

    Background: Despite adequate treatment with antipsychotics, a substantial number of patients with schizophrenia demonstrate only suboptimal clinical outcome. To overcome this challenge, various psychopharmacological combination strategies have been used, including antidepressants added to antipsychotics. Methods: To analyze the efficacy of add-on antidepressants for the treatment of negative, positive, cognitive, depressive, and antipsychotic-induced extrapyramidal symptoms in schizophrenia, published randomized controlled trials assessing the efficacy of adjunctive antidepressants in schizophrenia were reviewed using the following parameters: baseline clinical characteristics and number of patients, their on-going antipsychotic treatment, dosage of the add-on antidepressants, duration of the trial, efficacy measures, and outcomes. Results: There were 36 randomized controlled trials reported in 41 journal publications (n=1582). The antidepressants used were the selective serotonin reuptake inhibitors, duloxetine, imipramine, mianserin, mirtazapine, nefazodone, reboxetin, trazodone, and bupropion. Mirtazapine and mianserin showed somewhat consistent efficacy for negative symptoms and both seemed to enhance neurocognition. Trazodone and nefazodone appeared to improve the antipsychotics-induced extrapyramidal symptoms. Imipramine and duloxetine tended to improve depressive symptoms. No clear evidence supporting selective serotonin reuptake inhibitors’ efficacy on any clinical domain of schizophrenia was found. Add-on antidepressants did not worsen psychosis. Conclusions: Despite a substantial number of randomized controlled trials, the overall efficacy of add-on antidepressants in schizophrenia remains uncertain mainly due to methodological issues. Some differences in efficacy on several schizophrenia domains seem, however, to exist and to vary by the antidepressant subgroups—plausibly due to differences in the mechanisms of action. Antidepressants may not worsen

  17. Randomized phase II trial of sulindac for lung cancer chemoprevention.

    PubMed

    Limburg, Paul J; Mandrekar, Sumithra J; Aubry, Marie Christine; Ziegler, Katie L Allen; Zhang, Jun; Yi, Joanne E; Henry, Michael; Tazelaar, Henry D; Lam, Stephen; McWilliams, Annette; Midthun, David E; Edell, Eric S; Rickman, Otis B; Mazzone, Peter; Tockman, Melvyn; Beamis, John F; Lamb, Carla; Simoff, Michael; Loprinzi, Charles; Szabo, Eva; Jett, James

    2013-03-01

    Sulindac represents a promising candidate agent for lung cancer chemoprevention, but clinical trial data have not been previously reported. We conducted a randomized, phase II chemoprevention trial involving current or former cigarette smokers (≥30 pack-years) utilizing the multi-center, inter-disciplinary infrastructure of the Cancer Prevention Network (CPN). At least 1 bronchial dysplastic lesion identified by fluorescence bronchoscopy was required for randomization. Intervention assignments were sulindac 150mg bid or an identical placebo bid for 6 months. Trial endpoints included changes in histologic grade of dysplasia (per-participant as primary endpoint and per lesion as secondary endpoint), number of dysplastic lesions (per-participant), and Ki67 labeling index. Slower than anticipated recruitment led to trial closure after randomizing participants (n=31 and n=30 in the sulindac and placebo arms, respectively). Pre- and post-intervention fluorescence bronchoscopy data were available for 53/61 (87%) randomized, eligible participants. The median (range) of dysplastic lesions at baseline was 2 (1-12) in the sulindac arm and 2 (1-7) in the placebo arm. Change in dysplasia was categorized as regression:stable:progression for 15:3:8 (58%:12%:31%) subjects in the sulindac arm and 15:2:10 (56%:7%:37%) subjects in the placebo arm; these distributions were not statistically different (p=0.85). Median Ki67 expression (% cells stained positive) was significantly reduced in both the placebo (30 versus 5; p=0.0005) and sulindac (30 versus 10; p=0.0003) arms, but the difference between arms was not statistically significant (p=0.92). Data from this multi-center, phase II squamous cell lung cancer chemoprevention trial do not demonstrate sufficient benefits from sulindac 150mg bid for 6 months to warrant additional phase III testing. Investigation of pathway-focused agents is necessary for lung cancer chemoprevention. Copyright © 2012 Elsevier Ireland Ltd. All rights

  18. [Methodological reflections on 20 randomized clinical hydrotherapy trials in rheumatology].

    PubMed

    Queneau, P; Françon, A; Graber-Duvernay, B

    2001-01-01

    The aim of this study was to estimate the level of scientific evidence contributed by randomized clinical trials in rheumatologic indication of spa therapy. A literature search was made of computer data banks, with analysis of 20 randomized hydrotherapy trials. On the 20 identified randomized hydrotherapy trials, four were carried out double-blind; nine included a comparison of inter-groups evolution. The indications assessed are chronic low back pain, osteoarthritis of the knee and hip joints, osteoarthritis of fingers, fibromyalgia, rheumatoid arthritis and psoriasis arthritis. The results suggest durable, persisting improvement several months after balneological care, in accordance with the following evaluation criteria: pain, handicap, quality of life, consumption of analgesics and of nonsteroidal anti-inflammatory drugs (NSAIDs). It was concluded that randomized evaluations, demonstrating a beneficial and prolonged clinical effect of balneologic treatments, exist in respect of the main indications for rheumatologic hydrotherapy. These results acknowledge the medical help given by hydrotherapy within the aforesaid parameters, to which may be added a reduction of the adverse gastrointestinal events of NSAIDs. Evaluation needs to be continued to clarify the medical benefit offered by rheumatologic hydrotherapy.

  19. Randomized controlled trial design in rheumatoid arthritis: the past decade

    PubMed Central

    Strand, Vibeke; Sokolove, Jeremy

    2009-01-01

    Much progress has occurred over the past decade in rheumatoid arthritis trial design. Recognized challenges have led to the establishment of a clear regulatory pathway to demonstrate efficacy of a new therapeutic. The use of pure placebo beyond 12 to 16 weeks has been demonstrated to be unethical and thus background therapy and/or early rescue has become regular practice. Goals of remission and 'treating to targets' may prove more relevant to identify real-world use of new and existing therapeutics. Identification of rare adverse events associated with new therapies has resulted in intensive safety evaluation during randomized controlled trials and emphasis on postmarketing surveillance and use of registries. PMID:19232061

  20. Final Technical Report, DOE Grant DE-FG02-98ER54496, Physics of High-Energy-Density X Pinch Plasmas

    SciTech Connect

    David Hammer

    2008-12-03

    Abstract for the Final Technical Report, DOE Grant DE-FG02-98ER54496 An X-pinch plasma is produced by driving a high current (100-500 kiloamperes) through two or more fine wires that cross and touch at a point, forming an X in the case of two wires. The wires explode because of the high current, and then the resulting plasma is imploded radially inward by the magnetic field from the current. When the imploding material briefly stagnates at very small radius and high density, an intense burst of x-rays is produced and the plasma disassembles as rapidly as it imploded. When this project began, we could confidently state that at its minimum radius, X pinch plasmas made from such materials as titanium and molybdenum might be as hot as 10,000,000 K and had densities almost as high as the solid wire density, but their X-ray pulse durations were below one billionth of a second. We could also say that the X pinch was useful for point-projection imaging of rapidly changing objects, such as exploding wires, with high resolution, indicative of a very small X-ray source spot size. We can now confidently say that X-pinch plasma temperatures at the moment of the X-ray burst are 10-25 million K in titanium, molybdenum and several other wire X-pinches based upon the spectrum of emitted X-rays in the radiation burst. By the same means, as well as from the penetration of X-rays through the dense plasma, we know that ion densities are close to or higher than one-tenth of the density of the original (solid) wire material in molybdenum and a few other X-pinch plasmas. Furthermore, using the diffraction of X-rays radiated by the X-pinch when it reaches minimum radius, we have determined that the x-ray source size is about 1 thousandth of a millimeter for such wire materials as molybdenum and niobium, while it is 2-10 times larger for tungsten, titanium and aluminum wires. Finally, using a very high speed X-ray imaging “streak camera,” we have determined that X pinch X-ray pulses can

  1. Internet-based randomized controlled trials: a systematic review

    PubMed Central

    Mathieu, Erin; McGeechan, Kevin; Barratt, Alexandra; Herbert, Robert

    2013-01-01

    Background The internet is increasingly being used to conduct randomized controlled trials (RCTs). Knowledge of the types of interventions evaluated and the methodological quality of these trials could inform decisions about whether to conduct future trials using conventional methods, fully online or a mixture of the two. Objective To identify and describe the scope of internet-based RCTs for human health condition interventions and evaluate their methodological quality. Methods A systematic review of RCTs of any health intervention conducted fully or primarily on the internet was carried out. Results 23 fully and 27 primarily internet-based RCTs were identified. The first was conducted in 2000. The majority of trials evaluated interventions that involved providing health information to participants, but a few evaluated self-administered interventions (eg, valerian, stretching). Methodological quality was variable and the methods were generally poorly reported. The risk of bias was low in only a small number of trials; most had substantial methodological shortcomings. Only one trial was identified as meeting all criteria for adequate methodological quality. A particular problem was high rates of loss to follow-up (fully online: mean 47%; primarily online: mean 36%). Conclusions It is theoretically possible but perhaps difficult to test the effectiveness of health interventions rigorously with RCTs conducted fully or primarily over the internet. The use of the internet to conduct trials is more suited to pragmatic rather than explanatory trials. The main limitation of these trials is that they typically experience high rates of loss to follow-up. Methodological standards now accepted for traditional RCTs needs to be evident for online RCTs as well, especially in reporting of their methods. PMID:23065196

  2. Randomized trials are frequently fragmented in multiple secondary publications.

    PubMed

    Ebrahim, Shanil; Montoya, Luis; Kamal El Din, Mostafa; Sohani, Zahra N; Agarwal, Arnav; Bance, Sheena; Saquib, Juliann; Saquib, Nazmus; Ioannidis, John P A

    2016-11-01

    To assess the frequency and features of secondary publications of randomized controlled trials (RCTs). For 191 RCTs published in high-impact journals in 2009, we searched for secondary publications coauthored by at least one same author of the primary trial publication. We evaluated the probability of having secondary publications, characteristics of the primary trial publication that predict having secondary publications, types of secondary analyses conducted, and statistical significance of those analyses. Of 191 primary trials, 88 (46%) had a total of 475 secondary publications by 2/2014. Eight trials had >10 (up to 51) secondary publications each. In multivariable modeling, the risk of having subsequent secondary publications increased 1.32-fold (95% CI 1.05-1.68) per 10-fold increase in sample size, and 1.71-fold (95% CI 1.19-2.45) in the presence of a design article. In a sample of 197 secondary publications examined in depth, 193 tested different hypotheses than the primary publication. Of the 193, 43 tested differences between subgroups, 85 assessed predictive factors associated with an outcome of interest, 118 evaluated different outcomes than the original article, 71 had differences in eligibility criteria, and 21 assessed different durations of follow-up; 176 (91%) presented at least one analysis with statistically significant results. Approximately half of randomized trials in high-impact journals have secondary publications published with a few trials followed by numerous secondary publications. Almost all of these publications report some statistically significant results. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Antibiotics for human toxoplasmosis: a systematic review of randomized trials.

    PubMed

    Rajapakse, Senaka; Chrishan Shivanthan, Mitrakrishnan; Samaranayake, Nilakshi; Rodrigo, Chaturaka; Deepika Fernando, Sumadhya

    2013-06-01

    The efficacy of different treatment regimens in clinical syndromes of toxoplasmosis were assessed by conducting a systematic review of published randomized clinical trials through extensive searches in MEDLINE, EMBASE, and SCOPUS with no date limits, as well as manual review of journals. Outcome measures varied depending on the clinical entity of toxoplasmosis. Risk of bias was evaluated and quality of evidence was graded. Fourteen randomized trials were included of which one was a non-comparative study. One well-designed trial showed that trimethoprim-sulphamethoxazole was more effective than placebo for clinical recovery of toxoplasmic lymphadenopathy in immunocompetent hosts. For toxoplasmic encephalopathy, efficacy of pyrimethamine+sulphadiazine and trimethoprim+sulphamethoxazole were similar, whereas pyrimethamine+sulphadiazine versus pyrimathamine+clindamycin showed no difference, irrespective of the outcome. Intravitreal clindamycin+dexamethasone and conventional treatment with oral pyrimethamine+sulphadiazine had similar efficacy with regard to all outcome measures in ocular toxoplasmosis, and intravitreal therapy was found to be safe. Adverse effects seemed more common with pyrimethamine+sulphadiazine. Most trials for encephalitis and ocular manifestations had a high risk of bias and were of poor methodological quality. There were no trials evaluating drugs for toxoplasmosis in pregnancy, or for congenital toxoplasmosis. Pyrimethamine+sulphadiazine is an effective therapy for treatment of toxoplasmic encephalitis; trimethoprim+sulphamethoxazole and pyrimethamine+clindamycin are possible alternatives. Treatment with either oral or intravitreal antibiotics seems reasonable for ocular toxoplasmosis. Overall, trial evidence for the efficacy of these drugs for toxoplasmosis is poor, and further well-designed trials are needed.

  4. Randomized controlled trials – a matter of design

    PubMed Central

    Spieth, Peter Markus; Kubasch, Anne Sophie; Penzlin, Ana Isabel; Illigens, Ben Min-Woo; Barlinn, Kristian; Siepmann, Timo

    2016-01-01

    Randomized controlled trials (RCTs) are the hallmark of evidence-based medicine and form the basis for translating research data into clinical practice. This review summarizes commonly applied designs and quality indicators of RCTs to provide guidance in interpreting and critically evaluating clinical research data. It further reflects on the principle of equipoise and its practical applicability to clinical science with an emphasis on critical care and neurological research. We performed a review of educational material, review articles, methodological studies, and published clinical trials using the databases MEDLINE, PubMed, and ClinicalTrials.gov. The most relevant recommendations regarding design, conduction, and reporting of RCTs may include the following: 1) clinically relevant end points should be defined a priori, and an unbiased analysis and report of the study results should be warranted, 2) both significant and nonsignificant results should be objectively reported and published, 3) structured study design and performance as indicated in the Consolidated Standards of Reporting Trials statement should be employed as well as registration in a public trial database, 4) potential conflicts of interest and funding sources should be disclaimed in study report or publication, and 5) in the comparison of experimental treatment with standard care, preplanned interim analyses during an ongoing RCT can aid in maintaining clinical equipoise by assessing benefit, harm, or futility, thus allowing decision on continuation or termination of the trial. PMID:27354804

  5. Randomized Trial of a Web-Based Intervention to Address Barriers to Clinical Trials

    PubMed Central

    Wong, Yu-Ning; Albrecht, Terrance; Manne, Sharon; Miller, Suzanne M.; Flamm, Anne Lederman; Benson, Al Bowen; Buzaglo, Joanne; Collins, Michael; Egleston, Brian; Fleisher, Linda; Katz, Michael; Kinzy, Tyler G.; Liu, Tasnuva M.; Margevicius, Seunghee; Miller, Dawn M.; Poole, David; Roach, Nancy; Ross, Eric; Schluchter, Mark D.

    2016-01-01

    Purpose Lack of knowledge and negative attitudes have been identified as barriers to participation in clinical trials by patients with cancer. We developed Preparatory Education About Clinical Trials (PRE-ACT), a theory-guided, Web-based, interactive computer program, to deliver tailored video educational content to patients in an effort to overcome barriers to considering clinical trials as a treatment option. Patients and Methods A prospective, randomized clinical trial compared PRE-ACT with a control condition that provided general clinical trials information produced by the National Cancer Institute (NCI) in text format. One thousand two hundred fifty-five patients with cancer were randomly allocated before their initial visit with an oncologist to PRE-ACT (n = 623) or control (n = 632). PRE-ACT had three main components: assessment of clinical trials knowledge and attitudinal barriers, values assessment with clarification back to patients, and provision of a video library tailored to address each patient’s barriers. Outcomes included knowledge and attitudes and preparation for decision making about clinical trials. Results Both PRE-ACT and control interventions improved knowledge and attitudes (all P < .001) compared with baseline. Patients randomly allocated to PRE-ACT showed a significantly greater increase in knowledge (P < .001) and a significantly greater decrease in attitudinal barriers (P < .001) than did their control (text-only) counterparts. Participants in both arms significantly increased their preparedness to consider clinical trials (P < .001), and there was a trend favoring the PRE-ACT group (P < .09). PRE-ACT was also associated with greater patient satisfaction than was NCI text alone. Conclusion These data show that patient education before the first oncologist visit improves knowledge, attitudes, and preparation for decision making about clinical trials. Both text and tailored video were effective. The PRE-ACT interactive video program was

  6. Randomized Trial of a Web-Based Intervention to Address Barriers to Clinical Trials.

    PubMed

    Meropol, Neal J; Wong, Yu-Ning; Albrecht, Terrance; Manne, Sharon; Miller, Suzanne M; Flamm, Anne Lederman; Benson, Al Bowen; Buzaglo, Joanne; Collins, Michael; Egleston, Brian; Fleisher, Linda; Katz, Michael; Kinzy, Tyler G; Liu, Tasnuva M; Margevicius, Seunghee; Miller, Dawn M; Poole, David; Roach, Nancy; Ross, Eric; Schluchter, Mark D

    2016-02-10

    Lack of knowledge and negative attitudes have been identified as barriers to participation in clinical trials by patients with cancer. We developed Preparatory Education About Clinical Trials (PRE-ACT), a theory-guided, Web-based, interactive computer program, to deliver tailored video educational content to patients in an effort to overcome barriers to considering clinical trials as a treatment option. A prospective, randomized clinical trial compared PRE-ACT with a control condition that provided general clinical trials information produced by the National Cancer Institute (NCI) in text format. One thousand two hundred fifty-five patients with cancer were randomly allocated before their initial visit with an oncologist to PRE-ACT (n = 623) or control (n = 632). PRE-ACT had three main components: assessment of clinical trials knowledge and attitudinal barriers, values assessment with clarification back to patients, and provision of a video library tailored to address each patient's barriers. Outcomes included knowledge and attitudes and preparation for decision making about clinical trials. Both PRE-ACT and control interventions improved knowledge and attitudes (all P < .001) compared with baseline. Patients randomly allocated to PRE-ACT showed a significantly greater increase in knowledge (P < .001) and a significantly greater decrease in attitudinal barriers (P < .001) than did their control (text-only) counterparts. Participants in both arms significantly increased their preparedness to consider clinical trials (P < .001), and there was a trend favoring the PRE-ACT group (P < .09). PRE-ACT was also associated with greater patient satisfaction than was NCI text alone. These data show that patient education before the first oncologist visit improves knowledge, attitudes, and preparation for decision making about clinical trials. Both text and tailored video were effective. The PRE-ACT interactive video program was more effective than NCI text in improving

  7. Impact and Costs of Incentives to Reduce Attrition in Online Trials: Two Randomized Controlled Trials

    PubMed Central

    Murray, Elizabeth; Kalaitzaki, Eleftheria; White, Ian R; McCambridge, Jim; Thompson, Simon G; Wallace, Paul; Godfrey, Christine

    2011-01-01

    Background Attrition from follow-up is a major methodological challenge in randomized trials. Incentives are known to improve response rates in cross-sectional postal and online surveys, yet few studies have investigated whether they can reduce attrition from follow-up in online trials, which are particularly vulnerable to low follow-up rates. Objectives Our objective was to determine the impact of incentives on follow-up rates in an online trial. Methods Two randomized controlled trials were embedded in a large online trial of a Web-based intervention to reduce alcohol consumption (the Down Your Drink randomized controlled trial, DYD-RCT). Participants were those in the DYD pilot trial eligible for 3-month follow-up (study 1) and those eligible for 12-month follow-up in the DYD main trial (study 2). Participants in both studies were randomly allocated to receive an offer of an incentive or to receive no offer of an incentive. In study 1, participants in the incentive arm were randomly offered a £5 Amazon.co.uk gift voucher, a £5 charity donation to Cancer Research UK, or entry in a prize draw for £250. In study 2, participants in the incentive arm were offered a £10 Amazon.co.uk gift voucher. The primary outcome was the proportion of participants who completed follow-up questionnaires in the incentive arm(s) compared with the no incentive arm. Results In study 1 (n = 1226), there was no significant difference in response rates between those participants offered an incentive (175/615, 29%) and those with no offer (162/611, 27%) (difference = 2%, 95% confidence interval [CI] –3% to 7%). There was no significant difference in response rates among the three different incentives offered. In study 2 (n = 2591), response rates were 9% higher in the group offered an incentive (476/1296, 37%) than in the group not offered an incentive (364/1295, 28%) (difference = 9%, 95% CI 5% to 12%, P < .001). The incremental cost per extra successful follow-up in the incentive

  8. Bayesian population finding with biomarkers in a randomized clinical trial.

    PubMed

    Morita, Satoshi; Müller, Peter

    2017-03-03

    The identification of good predictive biomarkers allows investigators to optimize the target population for a new treatment. We propose a novel utility-based Bayesian population finding (BaPoFi) method to analyze data from a randomized clinical trial with the aim of finding a sensitive patient population. Our approach is based on casting the population finding process as a formal decision problem together with a flexible probability model, Bayesian additive regression trees (BART), to summarize observed data. The proposed method evaluates enhanced treatment effects in patient subpopulations based on counter-factual modeling of responses to new treatment and control for each patient. In extensive simulation studies, we examine the operating characteristics of the proposed method. We compare with a Bayesian regression-based method that implements shrinkage estimates of subgroup-specific treatment effects. For illustration, we apply the proposed method to data from a randomized clinical trial.

  9. Epicatechin, procyanidins, cocoa, and appetite: a randomized controlled trial.

    PubMed

    Greenberg, James A; O'Donnell, Ryan; Shurpin, Miriam; Kordunova, Dorina

    2016-09-01

    In 2 randomized controlled trials, it was reported that dark chocolate acutely decreased appetite in human subjects, but the authors did not assess the types or concentrations of cocoa compounds that are needed. Other studies have suggested that the cocoa compounds epicatechin and procyanidins may be involved. We sought to test the hypotheses that, compared with placebo (an alkalized cocoa mixture containing essentially no epicatechin or procyanidins), the following beverages cause a decrease in appetite: 1) a nonalkalized cocoa mixture; 2) epicatechin plus placebo; and 3) procyanidins plus placebo. We measured the concentrations of cocoa compounds in all beverages. We used a 4-way randomized, crossover, placebo-controlled trial that was balanced for period and carryover effects in 28 healthy, young-adult men. We also conducted a smaller (n = 14), parallel, secondary randomized trial in which we explored the effects of higher doses of epicatechin and procyanidins. Our primary measure of appetite was ad libitum pizza intake 150 min after beverage ingestion. We used a linear mixed-model analysis. Intakes of beverages with the nonalkalized cocoa mixture that contained 0.6 mg epicatechin, 0.2 mg catechin, and 2.9 mg monomer-decamer procyanidins/kg body weight did not decrease pizza intake significantly (P = 0.29) compared with intake of the placebo. In the smaller secondary trial, a combination of epicatechin and the nonalkalized cocoa mixture that contained 1.6 mg epicatechin/kg body weight significantly decreased pizza intake by 18.7% (P = 0.04). Our nonalkalized cocoa mixture was associated with an acute decrease in food intake only after being supplemented with epicatechin. It is possible that epicatechin at a dose of >1.6 mg/kg body weight, alone or in concert with appropriate catalytic cocoa compounds, may be useful for helping people control their food intakes. This trial was registered at clinicaltrials.gov as NCT02408289. © 2016 American Society for Nutrition.

  10. Statistical comparison of random allocation methods in cancer clinical trials.

    PubMed

    Hagino, Atsushi; Hamada, Chikuma; Yoshimura, Isao; Ohashi, Yasuo; Sakamoto, Junichi; Nakazato, Hiroaki

    2004-12-01

    The selection of a trial design is an important issue in the planning of clinical trials. One of the most important considerations in trial design is the method of treatment allocation and appropriate analysis plan corresponding to the design. In this article, we conducted computer simulations using the actual data from 2158 rectal cancer patients enrolled in the surgery-alone group from seven randomized controlled trials in Japan to compare the performance of allocation methods, simple randomization, stratified randomization and minimization in relatively small-scale trials (total number of two groups are 50, 100, 150 or 200 patients). The degree of imbalance in prognostic factors between groups was evaluated by changing the allocation probability of minimization from 1.00 to 0.70 by 0.05. The simulation demonstrated that minimization provides the best performance to ensure balance in the number of patients between groups and prognostic factors. Moreover, to achieve the 1 percentile for the p-value of chi-square test around 0.50 with respect to balance in prognostic factors, the allocation probability of minimization was required to be set to 0.95 for 50, 0.80 for 100, 0.75 for 150 and 0.70 for 200 patients. When the sample size was larger, sufficient balance could be achieved even if reducing allocation probability. The simulation using actual data demonstrated that unadjusted tests for the allocation factors resulted in conservative type I errors when dynamic allocation, such as minimization, was used. In contrast, adjusted tests for allocation factors as covariates improved type I errors closer to the nominal significance level and they provided slightly higher power. In conclusion, both the statistical and clinical validity of minimization was demonstrated in our study.

  11. Preconception maternal nutrition: a multi-site randomized controlled trial

    PubMed Central

    2014-01-01

    Background Research directed to optimizing maternal nutrition commencing prior to conception remains very limited, despite suggestive evidence of its importance in addition to ensuring an optimal nutrition environment in the periconceptional period and throughout the first trimester of pregnancy. Methods/Study design This is an individually randomized controlled trial of the impact on birth length (primary outcome) of the time at which a maternal nutrition intervention is commenced: Arm 1: ≥ 3 mo preconception vs. Arm 2: 12-14 wk gestation vs. Arm 3: none. 192 (derived from 480) randomized mothers and living offspring in each arm in each of four research sites (Guatemala, India, Pakistan, Democratic Republic of the Congo). The intervention is a daily 20 g lipid-based (118 kcal) multi-micronutient (MMN) supplement. Women randomized to receive this intervention with body mass index (BMI) <20 or whose gestational weight gain is low will receive an additional 300 kcal/d as a balanced energy-protein supplement. Researchers will visit homes biweekly to deliver intervention and monitor compliance, pregnancy status and morbidity; ensure prenatal and delivery care; and promote breast feeding. The primary outcome is birth length. Secondary outcomes include: fetal length at 12 and 34 wk; incidence of low birth weight (LBW); neonatal/infant anthropometry 0-6 mo of age; infectious disease morbidity; maternal, fetal, newborn, and infant epigenetics; maternal and infant nutritional status; maternal and infant microbiome; gut inflammatory biomarkers and bioactive and nutritive compounds in breast milk. The primary analysis will compare birth Length-for-Age Z-score (LAZ) among trial arms (independently for each site, estimated effect size: 0.35). Additional statistical analyses will examine the secondary outcomes and a pooled analysis of data from all sites. Discussion Positive results of this trial will support a paradigm shift in attention to nutrition of all females of

  12. Ear Acupuncture for Acute Sore Throat: A Randomized Controlled Trial

    DTIC Science & Technology

    2014-09-26

    SEP 2014 2. REPORT TYPE Final 3. DATES COVERED 4. TITLE AND SUBTITLE Ear acupuncture for acute sore throat. A randomized controlled trial...Auncular Acupuncture is a low risk option for acute pain control •Battlefield acupuncture (BFA) IS a specific auncular acupuncture technique •BFA IS...Strengths: Prospect1ve RCT •Weaknesses Small sample stze. no sham acupuncture performed, patients not blinded to treatment •Th1s study represents an

  13. Randomized trial of hyperthermia and radiation for superficial tumors.

    PubMed

    Jones, Ellen L; Oleson, James R; Prosnitz, Leonard R; Samulski, Thaddeus V; Vujaskovic, Zeljko; Yu, Daohai; Sanders, Linda L; Dewhirst, Mark W

    2005-05-01

    Randomized clinical trials have demonstrated hyperthermia (HT) enhances radiation response. These trials, however, generally lacked rigorous thermal dose prescription and administration. We report the final results of a prospective randomized trial of superficial tumors (trial was designed to test whether a thermal dose of more than 10 CEM 43 degrees C T(90) results in improved complete response and duration of local control compared with a thermal dose of randomly assigned to additional HT versus no additional HT. HT was given using microwave spiral strip applicators operating at 433 MHz. One hundred twenty-two patients were enrolled; 109 (89%) were deemed heatable and were randomly assigned. The complete response rate was 66.1% in the HT arm and 42.3% in the no-HT arm. The odds ratio for complete response was 2.7 (95% CI, 1.2 to 5.8; P = .02). Previously irradiated patients had the greatest incremental gain in complete response: 23.5% in the no-HT arm versus 68.2% in the HT arm. No overall survival benefit was seen. Adjuvant hyperthermia with a thermal dose more than 10 CEM 43 degrees C T(90) confers a significant local control benefit in patients with superficial tumors receiving radiation therapy.

  14. [Randomized controlled trials terminated prematurely: beneficial therapy effects].

    PubMed

    Kluth, L A; Rink, M; Ahyai, S A; Fisch, M; Shariat, S F; Dahm, P

    2013-08-01

    Randomized controlled trials (RCTs) stopped prematurely for beneficial therapy effects are becoming increasingly more prevalent in the urological literature and often receive great attention in the public and medical media. Urologists who practice evidence-based medicine should be aware of the potential bias and the different reasons why and how early termination of RCTs can and will affect the results. This review provides insights into the challenges clinical urologists face by interpreting the results of prematurely terminated RCTs.

  15. Reintegration the Role of Spouse Telephone Battlemind Randomized Clinical Trial

    DTIC Science & Technology

    2010-10-01

    Award Number: W81XWH-09-1-0242 TITLE: Reintegration The Role Of Spouse Telephone Battlemind Randomized Clinical Trial PRINCIPAL INVESTIGATOR...Iraq and Afghanistan service members. The goal is to build spouses’ resilience to cope with reintegration challenges, help them serve as a support...and family may have changed during deployment; negotiation; strategies to reduce or eliminate reintegration difficulties; strategies to support the

  16. Randomized clinical trials in orthodontics: reality, dream, or nightmare?

    PubMed

    Zuccati, Giliana; Clauser, Carlo; Giorgetti, Roberto

    2009-11-01

    Randomized controlled trials (RCTs) are considered the highest level in the hierarchy of evidence for treatment effectiveness. However, RCTs have also been criticized for various shortcomings. The purpose of this article was to review the most common criticisms against RCTs and answer them based on the principles of scientific inquiry, so that orthodontists can build their evidence-based practice on the best scientific research. In the era of evidence-based medicine, designing RCTs is the challenge for researchers in orthodontics.

  17. Automatic Generation of Randomized Trial Sequences for Priming Experiments

    PubMed Central

    Ihrke, Matthias; Behrendt, Jörg

    2011-01-01

    In most psychological experiments, a randomized presentation of successive displays is crucial for the validity of the results. For some paradigms, this is not a trivial issue because trials are interdependent, e.g., priming paradigms. We present a software that automatically generates optimized trial sequences for (negative-) priming experiments. Our implementation is based on an optimization heuristic known as genetic algorithms that allows for an intuitive interpretation due to its similarity to natural evolution. The program features a graphical user interface that allows the user to generate trial sequences and to interactively improve them. The software is based on freely available software and is released under the GNU General Public License. PMID:22007178

  18. Methodological survey of designed uneven randomization trials (DU-RANDOM): a protocol.

    PubMed

    Wu, Darong; Akl, Elie A; Guyatt, Gordon H; Devereaux, Philip J; Brignardello-Petersen, Romina; Prediger, Barbara; Patel, Krupesh; Patel, Namrata; Lu, Taoying; Zhang, Yuan; Falavigna, Maicon; Santesso, Nancy; Mustafa, Reem A; Zhou, Qi; Briel, Matthias; Schünemann, Holger J

    2014-01-23

    Although even randomization (that is, approximately 1:1 randomization ratio in study arms) provides the greatest statistical power, designed uneven randomization (DUR), (for example, 1:2 or 1:3) is used to increase participation rates. Until now, no convincing data exists addressing the impact of DUR on participation rates in trials. The objective of this study is to evaluate the epidemiology and to explore factors associated with DUR. We will search for reports of RCTs published within two years in 25 general medical journals with the highest impact factor according to the Journal Citation Report (JCR)-2010. Teams of two reviewers will determine eligibility and extract relevant information from eligible RCTs in duplicate and using standardized forms. We will report the prevalence of DUR trials, the reported reasons for using DUR, and perform a linear regression analysis to estimate the association between the randomization ratio and the associated factors, including participation rate, type of informed consent, clinical area, and so on. A clearer understanding of RCTs with DUR and its association with factors in trials, for example, participation rate, can optimize trial design and may have important implications for both researchers and users of the medical literature.

  19. Repeated randomization and matching in multi-arm trials.

    PubMed

    Xu, Zhenzhen; Kalbfleisch, John D

    2013-12-01

    Cluster randomized trials with relatively few clusters have been widely used in recent years for evaluation of health-care strategies. The balance match weighted (BMW) design, introduced in Xu and Kalbfleisch (2010, Biometrics 66, 813-823), applies the optimal full matching with constraints technique to a prospective randomized design with the aim of minimizing the mean squared error (MSE) of the treatment effect estimator. This is accomplished through consideration of M independent randomizations of the experimental units and then selecting the one which provides the most balance evaluated by matching on the estimated propensity scores. Often in practice, clinical trials may involve more than two treatment arms and multiple treatment options need to be evaluated. Therefore, we consider extensions of the BMW propensity score matching method to allow for studies with three or more arms. In this article, we propose three approaches to extend the BMW design to clinical trials with more than two arms and evaluate the property of the extended design in simulation studies.

  20. Reporting Methods of Blinding in Randomized Trials Assessing Nonpharmacological Treatments

    PubMed Central

    Boutron, Isabelle; Guittet, Lydia; Estellat, Candice; Moher, David; Hróbjartsson, Asbjørn; Ravaud, Philippe

    2007-01-01

    Background Blinding is a cornerstone of treatment evaluation. Blinding is more difficult to obtain in trials assessing nonpharmacological treatment and frequently relies on “creative” (nonstandard) methods. The purpose of this study was to systematically describe the strategies used to obtain blinding in a sample of randomized controlled trials of nonpharmacological treatment. Methods and Findings We systematically searched in Medline and the Cochrane Methodology Register for randomized controlled trials (RCTs) assessing nonpharmacological treatment with blinding, published during 2004 in high-impact-factor journals. Data were extracted using a standardized extraction form. We identified 145 articles, with the method of blinding described in 123 of the reports. Methods of blinding of participants and/or health care providers and/or other caregivers concerned mainly use of sham procedures such as simulation of surgical procedures, similar attention-control interventions, or a placebo with a different mode of administration for rehabilitation or psychotherapy. Trials assessing devices reported various placebo interventions such as use of sham prosthesis, identical apparatus (e.g., identical but inactivated machine or use of activated machine with a barrier to block the treatment), or simulation of using a device. Blinding participants to the study hypothesis was also an important method of blinding. The methods reported for blinding outcome assessors relied mainly on centralized assessment of paraclinical examinations, clinical examinations (i.e., use of video, audiotape, photography), or adjudications of clinical events. Conclusions This study classifies blinding methods and provides a detailed description of methods that could overcome some barriers of blinding in clinical trials assessing nonpharmacological treatment, and provides information for readers assessing the quality of results of such trials. PMID:17311468

  1. Preventing diabetes in primary care: a feasibility cluster randomized trial.

    PubMed

    Dawes, Diana; Ashe, Maureen; Campbell, Kristin; Cave, Douglas; Elley, C Raina; Kaczorowski, Janusz; Sohal, Parmjit; Ur, Ehud; Dawes, Martin

    2015-04-01

    To determine the feasibility of implementing a large-scale primary care-based diabetes prevention trial. A feasibility cluster randomized controlled trial was conducted in British Columbia, Canada, amongst adults with prediabetes using the Facilitated Lifestyle Intervention Prescription (FLIP) vs. usual care. FLIP included lifestyle advice, a pedometer, and telephone support from a lifestyle facilitator for 6 months. Indicators of feasibility included recruitment rates of family practices, participants and facilitators, as well as feasibility and retention rates in the FLIP program and study protocols. Six family practices participated; 59 patients were enrolled between October 2012 and March 2013. The trial protocol was acceptable to practices and participants and had a 95% participant retention rate over the 6 months (56/59). Adherence to the intervention was high (97%), with 34 of 35 patients continuing to receive telephone calls from the facilitator for 6 months. The mean cost of the intervention was C$144 per person. Compared with control, intervention participants significantly reduced weight by 3.2 kg (95% CI, 1.7 to 4.6); body mass index by 1.2 (95% CI, 0.7 to 1.7) and waist circumference by 3 cm (95% CI, 0.3 to 5.7). It is feasible to implement FLIP and to conduct a trial to assess effectiveness. A larger trial with longer follow up to assess progression to diabetes is warranted. Copyright © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  2. A RANDOMIZED TRIAL OF BIRTHING WITH AND WITHOUT STIRRUPS

    PubMed Central

    CORTON, Marlene M.; LANKFORD, Janice C.; AMES, Rebecca; MCINTIRE, Donald D.; ALEXANDER, James M.; LEVENO, Kenneth J.

    2012-01-01

    OBJECTIVE To determine if bed delivery without stirrups reduces the incidence of perineal lacerations compared to delivery in stirrups. STUDY DESIGN In this randomized trial we compared bed delivery without stirrups to delivery in stirrups in nulliparous women. The primary outcome was any perineal laceration (first- through fourth-degree). RESULTS 108 women were randomized to delivery without stirrups and 106 to stirrups. A total of 82 (76%) women randomized to no stirrups sustained perineal lacerations compared to 83 (78%) in women allocated to stirrups, p = .8. There was no significant difference in the severity of lacerations or in obstetric outcomes such as prolonged second stage of labor, forceps delivery, or cesarean birth. Similarly, infant outcomes were unaffected. CONCLUSION Our results do not incriminate stirrups as a cause of perineal lacerations. Alternatively, our findings of no difference in perineal lacerations suggest that delivering in bed without stirrups confers no advantages nor disadvantages. PMID:22840725

  3. A randomized controlled trial of an electronic informed consent process.

    PubMed

    Rothwell, Erin; Wong, Bob; Rose, Nancy C; Anderson, Rebecca; Fedor, Beth; Stark, Louisa A; Botkin, Jeffrey R

    2014-12-01

    A pilot study assessed an electronic informed consent model within a randomized controlled trial (RCT). Participants who were recruited for the parent RCT project were randomly selected and randomized to either an electronic consent group (n = 32) or a simplified paper-based consent group (n = 30). Results from the electronic consent group reported significantly higher understanding of the purpose of the study, alternatives to participation, and who to contact if they had questions or concerns about the study. However, participants in the paper-based control group reported higher mean scores on some survey items. This research suggests that an electronic informed consent presentation may improve participant understanding for some aspects of a research study. © The Author(s) 2014.

  4. The HONEYPOT randomized controlled trial statistical analysis plan.

    PubMed

    Pascoe, Elaine Mary; Lo, Serigne; Scaria, Anish; Badve, Sunil V; Beller, Elaine Mary; Cass, Alan; Hawley, Carmel Mary; Johnson, David W

    2013-01-01

    The HONEYPOT study is a multicenter, open-label, blinded-outcome, randomized controlled trial designed to determine whether, compared with standard topical application of mupirocin for nasal staphylococcal carriage, exit-site application of antibacterial honey reduces the rate of catheter-associated infections in peritoneal dialysis patients. To make public the pre-specified statistical analysis principles to be adhered to and the procedures to be performed by statisticians who will analyze the data for the HONEYPOT trial. Statisticians and clinical investigators who were blinded to treatment allocation and treatment-related study results and who will remain blinded until the central database is locked for final data extraction and analysis determined the statistical methods and procedures to be used for analysis and wrote the statistical analysis plan. The plan describes basic analysis principles, methods for dealing with a range of commonly encountered data analysis issues, and the specific statistical procedures for analyzing the primary, secondary, and safety outcomes. A statistical analysis plan containing the pre-specified principles, methods, and procedures to be adhered to in the analysis of the data from the HONEYPOT trial was developed in accordance with international guidelines. The structure and content of the plan provide sufficient detail to meet the guidelines on statistical principles for clinical trials produced by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. Making public the pre-specified statistical analysis plan for the HONEYPOT trial minimizes the potential for bias in the analysis of trial data and the interpretation and reporting of trial results.

  5. The HONEYPOT Randomized Controlled Trial Statistical Analysis Plan

    PubMed Central

    Pascoe, Elaine Mary; Lo, Serigne; Scaria, Anish; Badve, Sunil V.; Beller, Elaine Mary; Cass, Alan; Hawley, Carmel Mary; Johnson, David W.

    2013-01-01

    ♦ Background: The HONEYPOT study is a multicenter, open-label, blinded-outcome, randomized controlled trial designed to determine whether, compared with standard topical application of mupirocin for nasal staphylococcal carriage, exit-site application of antibacterial honey reduces the rate of catheter-associated infections in peritoneal dialysis patients. ♦ Objective: To make public the pre-specified statistical analysis principles to be adhered to and the procedures to be performed by statisticians who will analyze the data for the HONEYPOT trial. ♦ Methods: Statisticians and clinical investigators who were blinded to treatment allocation and treatment-related study results and who will remain blinded until the central database is locked for final data extraction and analysis determined the statistical methods and procedures to be used for analysis and wrote the statistical analysis plan. The plan describes basic analysis principles, methods for dealing with a range of commonly encountered data analysis issues, and the specific statistical procedures for analyzing the primary, secondary, and safety outcomes. ♦ Results: A statistical analysis plan containing the pre-specified principles, methods, and procedures to be adhered to in the analysis of the data from the HONEYPOT trial was developed in accordance with international guidelines. The structure and content of the plan provide sufficient detail to meet the guidelines on statistical principles for clinical trials produced by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. ♦ Conclusions: Making public the pre-specified statistical analysis plan for the HONEYPOT trial minimizes the potential for bias in the analysis of trial data and the interpretation and reporting of trial results. PMID:23843589

  6. Beyond the Randomized Controlled Trial: A Review of Alternatives in mHealth Clinical Trial Methods

    PubMed Central

    Wiljer, David; Cafazzo, Joseph A

    2016-01-01

    Background Randomized controlled trials (RCTs) have long been considered the primary research study design capable of eliciting causal relationships between health interventions and consequent outcomes. However, with a prolonged duration from recruitment to publication, high-cost trial implementation, and a rigid trial protocol, RCTs are perceived as an impractical evaluation methodology for most mHealth apps. Objective Given the recent development of alternative evaluation methodologies and tools to automate mHealth research, we sought to determine the breadth of these methods and the extent that they were being used in clinical trials. Methods We conducted a review of the ClinicalTrials.gov registry to identify and examine current clinical trials involving mHealth apps and retrieved relevant trials registered between November 2014 and November 2015. Results Of the 137 trials identified, 71 were found to meet inclusion criteria. The majority used a randomized controlled trial design (80%, 57/71). Study designs included 36 two-group pretest-posttest control group comparisons (51%, 36/71), 16 posttest-only control group comparisons (23%, 16/71), 7 one-group pretest-posttest designs (10%, 7/71), 2 one-shot case study designs (3%, 2/71), and 2 static-group comparisons (3%, 2/71). A total of 17 trials included a qualitative component to their methodology (24%, 17/71). Complete trial data collection required 20 months on average to complete (mean 21, SD 12). For trials with a total duration of 2 years or more (31%, 22/71), the average time from recruitment to complete data collection (mean 35 months, SD 10) was 2 years longer than the average time required to collect primary data (mean 11, SD 8). Trials had a moderate sample size of 112 participants. Two trials were conducted online (3%, 2/71) and 7 trials collected data continuously (10%, 7/68). Onsite study implementation was heavily favored (97%, 69/71). Trials with four data collection points had a longer study

  7. 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

  8. Electronic prompts significantly increase response rates to postal questionnaires: a randomized trial within a randomized trial and meta-analysis.

    PubMed

    Clark, Laura; Ronaldson, Sarah; Dyson, Lisa; Hewitt, Catherine; Torgerson, David; Adamson, Joy

    2015-12-01

    To assess the effectiveness of sending electronic prompts to randomized controlled trial participants to return study questionnaires. A "trial within a trial" embedded within a study determining the effectiveness of chronic obstructive pulmonary disease (DOC) screening on smoking cessation. Those participants taking part in DOC who provided a mobile phone number and/or an electronic mail address were randomized to either receive an electronic prompt or no electronic prompt to return a study questionnaire. The results were combined with two previous studies in a meta-analysis. A total of 437 participants were randomized: 226 to the electronic prompt group and 211 to the control group. A total of 285 (65.2%) participants returned the follow-up questionnaire: 157 (69.5%) in the electronic prompt group and 128 (60.7%) in the control group [difference 8.8%; 95% confidence interval (CI): -0.11%, 17.7%; P = 0.05]. The mean time to response was 23 days in the electronic prompt group and 33 days in the control group (hazard ratio = 1.27; 95% CI: 1.105, 1.47). The meta-analysis of all three studies showed an increase in response rate of 7.1% (95% CI: 0.8%, 13.3%). The use of electronic prompts increased response rates and reduces the time to response. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Financial management of a large multisite randomized clinical trial.

    PubMed

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

    2014-08-01

    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 2500 randomized participants at 40 sites. 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. 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. 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 2500 targeted sample size, 138 (5·5%) were randomized during the first five years and 1387 (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. 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. © 2014 The Authors. International Journal of Stroke © 2014 World Stroke Organization.

  10. Fertility after ectopic pregnancy: the DEMETER randomized trial.

    PubMed

    Fernandez, Hervé; Capmas, Perrine; Lucot, Jean Philippe; Resch, Benoit; Panel, Pierre; Bouyer, Jean

    2013-05-01

    Does treatment for the resolution of ectopic pregnancy (EP) affect subsequent spontaneous fertility [occurrence of an intrauterine pregnancy (IUP)]? There is no significant difference in 2 years subsequent fertility neither between methotrexate and conservative surgery for less active EP nor between conservative and radical surgery for the most active EP. No randomized trial has compared radical and conservative surgery treatments. A recent review of the Cochrane database did not conclude about fertility due to insufficient data. Prospective studies from EP registries in two regions of France (Auvergne and Greater Lille) have suggested that fertility is similar after medical treatment and conservative surgery and lower after radical surgery. This randomized controlled trial included all women with an ultrasound-confirmed EP. Women were divided into two arms according to the activity of the EP (defined by Fernandez's score). In arm 1 (less active ectopic pregnancies, i.e. Fernandez's score <13 and no haemodynamic failure), medical treatment was considered practicable, and women were randomly allocated to conservative surgery with a systematic post-operative i.m. methotrexate injection within 24 h or to an i.m. methotrexate injection alone. In arm 2 (active ectopic pregnancies), medical treatment was considered impracticable, and, thus, all women had to undergo surgery; they were randomly allocated to either a radical or conservative procedure, the latter including a post-operative methotrexate injection. Sample sizes (n = 210 in arm 1 and n = 230 in arm 2) were computed to provide a statistical power of 80% to detect a 20% difference in subsequent cumulative fertility rates between treatments in each arm. The total duration of the trial was 5 years. The trial took place in 17 centres in France from 2005 to 2009. Two hundred and seven women were included in arm 1 and 199 in arm 2. Cumulative fertility curves were drawn with the Kaplan-Meier method and compared with

  11. Lowering of glucose in critical care: a randomized pilot trial.

    PubMed

    McMullin, Joseph; Brozek, Jan; McDonald, Ellen; Clarke, France; Jaeschke, Roman; Heels-Ansdell, Diane; Leppert, Ryan; Foss, Anders; Cook, Deborah

    2007-06-01

    Similar to cardiac surgery patients, medical-surgical critically ill patients may benefit from intensive insulin therapy. The objectives of this pilot trial were to evaluate the feasibility of a randomized trial of intensive insulin therapy with respect to (a) achieving target glucose values in the 2 ranges of 5 to 7 and 8 to 10 mmol/L and (b) uncovering problems with the protocol in anticipation of a larger trial. The trial was conducted in a 15-bed medical-surgical university-affiliated intensive care unit (ICU). We included patients older than 18 years, expected to be in ICU for more than 72 hours, with a glucose value of more than 10 mmol/L within 48 hours of ICU admission. Exclusion criteria were diabetic ketoacidosis, severe hepatic failure or hepatic resection, pancreatitis, glucose of less than 2.2 mmol/L on admission to hospital, insulin infusion on admission to ICU, planned withdrawal of life support, and inability to obtain informed consent. Patients underwent concealed random allocation to a target glucose range of 5 to 7 or 8 to 10 mmol/L using pretested algorithms of insulin infusions. Dedicated glucometer measurement of arterial glucose values was calibrated daily to values measured in the laboratory. We enrolled 20 patients with a mean (SD) Acute Physiology and Chronic Health Evaluation (APACHE) II score of 32 (10.2); 14 were insulin-dependent pre-ICU, and all were medical admissions. Mean glucose values were different in the 2 groups (7.1 +/- 2.6 vs 9.4 +/- 2.1 mmol/L, P < .001). Although the intensive insulin therapy group had more glucose measurements performed than the control group, a similar proportion of values were within the target range (682 [42.4%] of 1607 values in the 5- to 7-mmol/L range; 250 [38.7%] of 660 values in the 8- to 10-mmol/L range, P = .35). Glucose values of less than 2.5 mmol/L developed 7 times in 5 patients, 4 of whom were in the intensive insulin therapy group; however, no adverse consequences were documented. As

  12. Power Calculations for Moderators in Multi-Site Cluster Randomized Trials

    ERIC Educational Resources Information Center

    Spybrook, Jessaca; Kelcey, Ben; Dong, Nianbo

    2016-01-01

    Cluster randomized trials (CRTs), or studies in which intact groups of individuals are randomly assigned to a condition, are becoming more common in evaluation studies of educational programs. A specific type of CRT in which clusters are randomly assigned to treatment within blocks or sites, known as multisite cluster randomized trials (MSCRTs),…

  13. Standardization for subgroup analysis in randomized controlled trials.

    PubMed

    Varadhan, Ravi; Wang, Sue-Jane

    2014-01-01

    Randomized controlled trials (RCTs) emphasize the average or overall effect of a treatment (ATE) on the primary endpoint. Even though the ATE provides the best summary of treatment efficacy, it is of critical importance to know whether the treatment is similarly efficacious in important, predefined subgroups. This is why the RCTs, in addition to the ATE, also present the results of subgroup analysis for preestablished subgroups. Typically, these are marginal subgroup analysis in the sense that treatment effects are estimated in mutually exclusive subgroups defined by only one baseline characteristic at a time (e.g., men versus women, young versus old). Forest plot is a popular graphical approach for displaying the results of subgroup analysis. These plots were originally used in meta-analysis for displaying the treatment effects from independent studies. Treatment effect estimates of different marginal subgroups are, however, not independent. Correlation between the subgrouping variables should be addressed for proper interpretation of forest plots, especially in large effectiveness trials where one of the goals is to address concerns about the generalizability of findings to various populations. Failure to account for the correlation between the subgrouping variables can result in misleading (confounded) interpretations of subgroup effects. Here we present an approach called standardization, a commonly used technique in epidemiology, that allows for valid comparison of subgroup effects depicted in a forest plot. We present simulations results and a subgroup analysis from parallel-group, placebo-controlled randomized trials of antibiotics for acute otitis media.

  14. Randomized clinical trial of interceptive and comprehensive orthodontics.

    PubMed

    King, G J; Spiekerman, C F; Greenlee, G M; Huang, G J

    2012-07-01

    Focusing public insurance programs on interceptive orthodontics (IO) may increase access for low-income children. This report presents outcomes from a randomized clinical trial (RCT) comparing IO with comprehensive orthodontics (CO) in Medicaid patients. One hundred seventy pre-adolescents with Medicaid-eligible malocclusions were randomized to IO (n = 86) followed by observation (OBS) or OBS followed by CO (n = 84). One hundred thirty-four completed the trial. Models at pre-treatment (baseline) and following ≤ 2 years of intervention and 2 years of OBS (48 mos) were scored by calibrated examiners using the Peer Assessment Rating (PAR) and Index of Complexity, Outcome and Need (ICON). Overall outcomes and clinically meaningful categorical ICON data on need/acceptability, complexity, and improvement were compared. At baseline, groups were balanced by age, gender, ethnicity, and PAR/ICON scores. Most were minorities. Most (77%) were rated as difficult-to-very difficult. Scores improved significantly for both groups, but CO more than IO (PAR, 18.6 [95%CI 15.1, 22.1] vs.10.1 [95%CI 6.7, 13.4]; ICON, 44.8 [95% CI 39.7, 49.9] vs. 35.2 [95%CI 29.7, 40.6], respectively). On average, IO is effective at reducing malocclusions in Medicaid patients, but less than CO. (ClinicalTrials.gov number CT00067379).

  15. Randomized Clinical Trial of Interceptive and Comprehensive Orthodontics

    PubMed Central

    King, G.J.; Spiekerman, C.F.; Greenlee, G.M.; Huang, G.J.

    2012-01-01

    Focusing public insurance programs on interceptive orthodontics (IO) may increase access for low-income children. This report presents outcomes from a randomized clinical trial (RCT) comparing IO with comprehensive orthodontics (CO) in Medicaid patients. One hundred seventy pre-adolescents with Medicaid-eligible malocclusions were randomized to IO (n = 86) followed by observation (OBS) or OBS followed by CO (n = 84). One hundred thirty-four completed the trial. Models at pre-treatment (baseline) and following ≤ 2 years of intervention and 2 years of OBS (48 mos) were scored by calibrated examiners using the Peer Assessment Rating (PAR) and Index of Complexity, Outcome and Need (ICON). Overall outcomes and clinically meaningful categorical ICON data on need/acceptability, complexity, and improvement were compared. At baseline, groups were balanced by age, gender, ethnicity, and PAR/ICON scores. Most were minorities. Most (77%) were rated as difficult-to-very difficult. Scores improved significantly for both groups, but CO more than IO (PAR, 18.6 [95%CI 15.1, 22.1] vs.10.1 [95%CI 6.7, 13.4]; ICON, 44.8 [95% CI 39.7, 49.9] vs. 35.2 [95%CI 29.7, 40.6], respectively). On average, IO is effective at reducing malocclusions in Medicaid patients, but less than CO. (ClinicalTrials.gov number CT00067379) PMID:22699670

  16. The Sexunzipped trial: optimizing the design of online randomized controlled trials.

    PubMed

    Bailey, Julia V; Pavlou, Menelaos; Copas, Andrew; McCarthy, Ona; Carswell, Ken; Rait, Greta; Hart, Graham; Nazareth, Irwin; Free, Caroline; French, Rebecca; Murray, Elizabeth

    2013-12-11

    Sexual health problems such as unwanted pregnancy and sexually transmitted infection are important public health concerns and there is huge potential for health promotion using digital interventions. Evaluations of digital interventions are increasingly conducted online. Trial administration and data collection online offers many advantages, but concerns remain over fraudulent registration to obtain compensation, the quality of self-reported data, and high attrition. This study addresses the feasibility of several dimensions of online trial design-recruitment, online consent, participant identity verification, randomization and concealment of allocation, online data collection, data quality, and retention at 3-month follow-up. Young people aged 16 to 20 years and resident in the United Kingdom were recruited to the "Sexunzipped" online trial between November 2010 and March 2011 (n=2036). Participants filled in baseline demographic and sexual health questionnaires online and were randomized to the Sexunzipped interactive intervention website or to an information-only control website. Participants were also randomly allocated to a postal request (or no request) for a urine sample for genital chlamydia testing and receipt of a lower (£10/US$16) or higher (£20/US$32) value shopping voucher compensation for 3-month outcome data. The majority of the 2006 valid participants (90.98%, 1825/2006) were aged between 18 and 20 years at enrolment, from all four countries in the United Kingdom. Most were white (89.98%, 1805/2006), most were in school or training (77.48%, 1545/1994), and 62.81% (1260/2006) of the sample were female. In total, 3.88% (79/2036) of registrations appeared to be invalid and another 4.00% (81/2006) of participants gave inconsistent responses within the questionnaire. The higher value compensation (£20/US$32) increased response rates by 6-10%, boosting retention at 3 months to 77.2% (166/215) for submission of online self-reported sexual health

  17. Validation of Placebo in a Manual Therapy Randomized Controlled Trial

    PubMed Central

    Chaibi, Aleksander; Šaltytė Benth, Jūratė; Bjørn Russell, Michael

    2015-01-01

    At present, no consensus exists among clinical and academic experts regarding an appropriate placebo for randomized controlled trials (RCTs) of spinal manipulative therapy (SMT). Therefore, we investigated whether it was possible to conduct a chiropractic manual-therapy RCT with placebo. Seventy migraineurs were randomized to a single-blinded placebo-controlled clinical trial that consisted of 12 treatment sessions over 3 months. The participants were randomized to chiropractic SMT or placebo (sham manipulation). After each session, the participants were surveyed on whether they thought they had undergone active treatment (“yes” or “no”) and how strongly they believed that active treatment was received (numeric rating scale 0–10). The outcome measures included the rate of successful blinding and the certitude of the participants’ beliefs in both treatment groups. At each treatment session, more than 80% of the participants believed that they had undergone active treatment, regardless of group allocation. The odds ratio for believing that active treatment was received was >10 for all treatment sessions in both groups (all p < 0.001). The blinding was maintained throughout the RCT. Our results strongly demonstrate that it is possible to conduct a single-blinded manual-therapy RCT with placebo and to maintain the blinding throughout 12 treatment sessions given over 3 months. PMID:26145718

  18. Validation of Placebo in a Manual Therapy Randomized Controlled Trial.

    PubMed

    Chaibi, Aleksander; Šaltytė Benth, Jūratė; Bjørn Russell, Michael

    2015-07-06

    At present, no consensus exists among clinical and academic experts regarding an appropriate placebo for randomized controlled trials (RCTs) of spinal manipulative therapy (SMT). Therefore, we investigated whether it was possible to conduct a chiropractic manual-therapy RCT with placebo. Seventy migraineurs were randomized to a single-blinded placebo-controlled clinical trial that consisted of 12 treatment sessions over 3 months. The participants were randomized to chiropractic SMT or placebo (sham manipulation). After each session, the participants were surveyed on whether they thought they had undergone active treatment ("yes" or "no") and how strongly they believed that active treatment was received (numeric rating scale 0-10). The outcome measures included the rate of successful blinding and the certitude of the participants' beliefs in both treatment groups. At each treatment session, more than 80% of the participants believed that they had undergone active treatment, regardless of group allocation. The odds ratio for believing that active treatment was received was >10 for all treatment sessions in both groups (all p < 0.001). The blinding was maintained throughout the RCT. Our results strongly demonstrate that it is possible to conduct a single-blinded manual-therapy RCT with placebo and to maintain the blinding throughout 12 treatment sessions given over 3 months.

  19. Prospective randomized trial of ketorolac after congenital heart surgery.

    PubMed

    Gupta, Anuja; Daggett, Casey; Drant, Stacey; Rivero, Niurka; Lewis, Alan

    2004-08-01

    Ketorolac is a potent nonsteroidal analgesic agent used to treat postoperative pain. It produces excellent analgesia without the sedating side effects of opioid analgesics. Routine use of ketorolac after cardiac surgery is limited by concerns of bleeding complications. The purpose of this study was to evaluate the risk of bleeding complications of ketorolac for treatment of pain after congenital heart surgery in infants and children. Prospective randomized, controlled trial. Pediatric cardiac intensive care unit in tertiary teaching hospital. Seventy infants and children, median age 10 months (range 2.5-174), who underwent congenital heart surgery requiring cardiopulmonary bypass were randomized in the trial. Pain control was performed with ketorolac and opioid analgesics in one arm of the study and opioid analgesics alone in the other arm. The main outcome evaluated was bleeding complications measured by chest-tube drainage and wound and gastrointestinal bleeding. Thirty-five patients were randomized to each treatment arm. In the ketorolac group, the median chest-tube drainage was 13.3 (range 4-22) mL/kg/d, no patient had significant wound bleeding, and 1 (0.03%) patient had gastrointestinal bleeding. In the control group, the median chest-tube drainage was 16.5 (range 3-24) mL/kg/d, 1 (0.03%) patient had wound bleeding, and no patient had gastrointestinal bleeding. Ketorolac can be used to treat pain after congenital heart surgery without an increased risk of bleeding complications.

  20. Randomized controlled trials to assess therapies for multiple sclerosis.

    PubMed

    Wingerchuk, Dean M; Noseworthy, John H

    2002-04-23

    MS poses formidable challenges to clinical investigators. Obstacles to the study of MS therapies include disease chronicity, an unpredictable clinical course, radiologic and pathologic heterogeneity, and limited understanding of the underlying pathophysiology. Randomized controlled trials (RCTs) provide a means to assess therapeutic efficacy while reducing the risks of study bias and confounding factors that influence interpretation of results. RCTs have demonstrated that type 1 interferons and glatiramer acetate alter the short-term natural history of MS and have served as the basis of approval for the marketing of these treatments. Improvements and optimization of trial methodology may hasten the discovery of effective therapies and facilitate better comparisons of the results of individual drug trials. The most urgent need is for improved surrogate end points for clinical outcome with predictive validity for long-term disability. Even if RCT methodology is optimal, however, several limitations inherent to MS trials threaten to impede further progress, including obstacles to long-term studies (e.g., costs), patient withdrawal, and escalating sample size requirements to detect partial therapeutic benefit. There is a crucial need to develop alternative investigative methods, possibly through enhanced collaboration across centers and with industry, and by exploring innovative techniques to use existing RCT and natural history databases to greater advantage.

  1. Randomized controlled trials for Alzheimer disease and Parkinson disease.

    PubMed

    Lauretani, Fulvio; Ticinesi, Andrea; Meschi, Tiziana; Teresi, Giulio; Ceda, Gian Paolo; Maggio, Marcello

    2016-06-01

    The continuous increase in elderly and oldest-old population, and subsequent rise in prevalence of chronic neurological diseases like Alzheimer's disease (AD) and Parkinson's disease (PD), are a major challenge for healthcare systems. These two conditions are the most prevalent neurodegenerative diseases in older persons and physicians should engage treatment for these patients. In this field, Randomized Clinical Trials (RCTs) specifically focused on elderly populations are still lacking. The aim of this study was to identify RCTs conducted among AD and PD and to examine the difference between mean age of enrollment and incidence of these two neurodegenerative diseases. We found that the scenario is different between PD and AD. In particular, the enrollment for PD trials seems to include younger persons than AD, although the incidence of both diseases is similar and highest after 80 years old. The consequence of these results could influence conclusive guidelines of treatment in older parkinsonian patients.

  2. 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

  3. Individual placement and support in Sweden - a randomized controlled trial.

    PubMed

    Bejerholm, Ulrika; Areberg, Cecilia; Hofgren, Caisa; Sandlund, Mikael; Rinaldi, Miles

    2015-01-01

    Currently there is no evidence on the effectiveness of Individual Placement and Support (IPS) in Sweden. To determine the effectiveness of IPS on vocational outcomes among people with severe mental illness (SMI) in a Swedish context. A secondary aim was to evaluate a community integration effect. A randomized controlled trial with a parallel design was used. Mental health outpatients with SMI were randomized to IPS or traditional vocational rehabilitation (TVR) services. The allocation status was assessor-blinded. The primary outcome was competitive employment. All vocational outcomes were collected continuously, and socio-demographic and clinical variables at baseline, 6 and 18 months. The trial is registered with ClinicalTrials.gov: NCT00960024. One hundred and twenty participants were randomized. Eighty seven per cent were assessed after 6 months, and 73% after 18 months. IPS was more effective than TVR in terms of gaining employment at 18-month follow-up (46% vs. 11%; difference 36%, 95% CI 18-54), along with the amount of working hours and weeks, longer job tenure periods and income. Cox regression analysis showed that IPS participants gained employment five times quicker than those in TVR. Ninety per cent of the IPS participants became involved in work, internships or education, i.e. activities integrated in mainstream community settings, while 24% in the TVR group achieved this. IPS is effective in a Swedish context in terms of gaining employment and becoming integrated within the local community. The welfare system presented obstacles for gaining competitive employment directly and it was indicated that internships delayed time to first competitive employment.

  4. A Randomized trial of an Asthma Internet Self-management Intervention (RAISIN): study protocol for a randomized controlled trial.

    PubMed

    Morrison, Deborah; Wyke, Sally; Thomson, Neil C; McConnachie, Alex; Agur, Karolina; Saunderson, Kathryn; Chaudhuri, Rekha; Mair, Frances S

    2014-05-24

    The financial costs associated with asthma care continue to increase while care remains suboptimal. Promoting optimal self-management, including the use of asthma action plans, along with regular health professional review has been shown to be an effective strategy and is recommended in asthma guidelines internationally. Despite evidence of benefit, guided self-management remains underused, however the potential for online resources to promote self-management behaviors is gaining increasing recognition. The aim of this paper is to describe the protocol for a pilot evaluation of a website 'Living well with asthma' which has been developed with the aim of promoting self-management behaviors shown to improve outcomes. The study is a parallel randomized controlled trial, where adults with asthma are randomly assigned to either access to the website for 12 weeks, or usual asthma care for 12 weeks (followed by access to the website if desired). Individuals are included if they are over 16-years-old, have a diagnosis of asthma with an Asthma Control Questionnaire (ACQ) score of greater than, or equal to 1, and have access to the internet. Primary outcomes for this evaluation include recruitment and retention rates, changes at 12 weeks from baseline for both ACQ and Asthma Quality of Life Questionnaire (AQLQ) scores, and quantitative data describing website usage (number of times logged on, length of time logged on, number of times individual pages looked at, and for how long). Secondary outcomes include clinical outcomes (medication use, health services use, lung function) and patient reported outcomes (including adherence, patient activation measures, and health status). Piloting of complex interventions is considered best practice and will maximise the potential of any future large-scale randomized controlled trial to successfully recruit and be able to report on necessary outcomes. Here we will provide results across a range of outcomes which will provide estimates of

  5. An Update on Randomized Clinical Trials in Metastatic Colorectal Carcinoma.

    PubMed

    Ikoma, Naruhiko; Raghav, Kanwal; Chang, George

    2017-10-01

    There have been remarkable advances in the treatment of metastatic colorectal cancer over the past 20 years, chiefly achieved by development of new active drugs and establishment of effective systemic therapy regimens. Multidisciplinary care of resectable liver disease with use of perioperative systemic therapy and superior liver resection has resulted in prolonged survival of select patients. Median overall survival has significantly improved with the modern multiagent regimens. This article reviews recent high-quality randomized clinical trials that were conducted to address optimal treatment of advanced and metastatic colorectal carcinoma, mainly focused on initially inoperable metastatic disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Neighborhood Effects in a Behavioral Randomized Controlled Trial

    PubMed Central

    Pruitt, Sandi L.; Leonard, Tammy; Murdoch, James; Hughes, Amy; McQueen, Amy; Gupta, Samir

    2015-01-01

    Randomized controlled trials (RCTs) of interventions intended to modify health behaviors may be influenced by neighborhood effects which can impede unbiased estimation of intervention effects. Examining a RCT designed to increase colorectal cancer (CRC) screening (N=5,628), we found statistically significant neighborhood effects: average CRC test use among neighboring study participants was significantly and positively associated with individual patient’s CRC test use. This potentially important spatially-varying covariate has not previously been considered in a RCT. Our results suggest that future RCTs of health behavior interventions should assess potential social interactions between participants, which may cause intervention arm contamination and may bias effect size estimation. PMID:25456014

  7. Decision Aids Can Support Cancer Clinical Trials Decisions: Results of a Randomized Trial.

    PubMed

    Politi, Mary C; Kuzemchak, Marie D; Kaphingst, Kimberly A; Perkins, Hannah; Liu, Jingxia; Byrne, Margaret M

    2016-12-01

    Cancer patients often do not make informed decisions regarding clinical trial participation. This study evaluated whether a web-based decision aid (DA) could support trial decisions compared with our cancer center's website. Adults diagnosed with cancer in the past 6 months who had not previously participated in a cancer clinical trial were eligible. Participants were randomized to view the DA or our cancer center's website (enhanced usual care [UC]). Controlling for whether participants had heard of cancer clinical trials and educational attainment, multivariable linear regression examined group on knowledge, self-efficacy for finding trial information, decisional conflict (values clarity and uncertainty), intent to participate, decision readiness, and trial perceptions. Two hundred patients (86%) consented between May 2014 and April 2015. One hundred were randomized to each group. Surveys were completed by 87 in the DA group and 90 in the UC group. DA group participants reported clearer values regarding trial participation than UC group participants reported (least squares [LS] mean = 15.8 vs. 32, p < .0001) and less uncertainty (LS mean = 24.3 vs. 36.4, p = .025). The DA group had higher objective knowledge than the UC group's (LS mean = 69.8 vs. 55.8, p < .0001). There were no differences between groups in intent to participate. Improvements on key decision outcomes including knowledge, self-efficacy, certainty about choice, and values clarity among participants who viewed the DA suggest web-based DAs can support informed decisions about trial participation among cancer patients facing this preference-sensitive choice. Although better informing patients before trial participation could improve retention, more work is needed to examine DA impact on enrollment and retention. This paper describes evidence regarding a decision tool to support patients' decisions about trial participation. By improving knowledge, helping patients clarify preferences for

  8. Aromatherapy and behaviour disturbances in dementia: a randomized controlled trial.

    PubMed

    Smallwood, J; Brown, R; Coulter, F; Irvine, E; Copland, C

    2001-10-01

    A random controlled trial of the relaxing effects of an aromatherapy massage on disordered behaviour in dementia was conducted. Twenty-one patients were randomly allocated into one of three conditions, aromatherapy and massage (AM), conversation and aromatherapy (CA) and massage only (M). AM showed the greatest reduction in the frequency of excessive motor behaviour of all three conditions. This reached statistical significance between the hours of three and four pm (p < 0.05). Post hoc analysis suggested that at this time of day the AM consistently reduced motor behaviour when compared with CA (p = 0.05). This provides preliminary evidence of a measurable sedative effect of aromatherapy massage on dementia within a robust scientific paradigm. Further research is recommended with an expanded sample size. Copyright 2001 John Wiley & Sons, Ltd.

  9. Drug versus placebo randomized controlled trials in neonates: A review of ClinicalTrials.gov registry

    PubMed Central

    Desselas, Emilie; Pansieri, Claudia; Leroux, Stephanie; Bonati, Maurizio; Jacqz-Aigrain, Evelyne

    2017-01-01

    Background Despite specific initiatives and identified needs, most neonatal drugs are still used off-label, with variable dosage administrations and schedules. In high risk preterm and term neonates, drug evaluation is challenging and randomized controlled trials (RCT) are difficult to conduct and even more is the use of a placebo, required in the absence of a reference validated drug to be used as comparator. Methods We analyzed the complete ClinicalTrials.gov registry 1) to describe neonatal RCT involving a placebo, 2) to report on the medical context and ethical aspects of placebo use. Results Placebo versus drug RCT (n = 146), either prevention trials (n = 57, 39%) or therapeutic interventions (n = 89, 61%), represent more than a third of neonatal trials registered in the National Institute of Health clinical trial database (USA) since 1999. They mainly concerned preterm infants, evaluating complications of prematurity. Most trials were conducted in the USA, were single centered, and funded by non-profit organizations. For the three top drug trials evaluating steroids (n = 13, 9.6%), erythropoietin (EPO, n = 10, 6.8%) and nitric oxide (NO, n = 9, 6.2%), the objectives of the trial and follow-up were analyzed in more details. Conclusion Although a matter of debate, the use of placebo should be promoted in neonates to evaluate a potential new treatment, in the absence of reference drug. Analysis of the trials evaluating steroids showed that long-term follow-up of exposed patients, although required by international guidelines, is frequently missing and should be planned to collect additional information and optimize drug evaluation in these high-risk patients. PMID:28192509

  10. Drug versus placebo randomized controlled trials in neonates: A review of ClinicalTrials.gov registry.

    PubMed

    Desselas, Emilie; Pansieri, Claudia; Leroux, Stephanie; Bonati, Maurizio; Jacqz-Aigrain, Evelyne

    2017-01-01

    Despite specific initiatives and identified needs, most neonatal drugs are still used off-label, with variable dosage administrations and schedules. In high risk preterm and term neonates, drug evaluation is challenging and randomized controlled trials (RCT) are difficult to conduct and even more is the use of a placebo, required in the absence of a reference validated drug to be used as comparator. We analyzed the complete ClinicalTrials.gov registry 1) to describe neonatal RCT involving a placebo, 2) to report on the medical context and ethical aspects of placebo use. Placebo versus drug RCT (n = 146), either prevention trials (n = 57, 39%) or therapeutic interventions (n = 89, 61%), represent more than a third of neonatal trials registered in the National Institute of Health clinical trial database (USA) since 1999. They mainly concerned preterm infants, evaluating complications of prematurity. Most trials were conducted in the USA, were single centered, and funded by non-profit organizations. For the three top drug trials evaluating steroids (n = 13, 9.6%), erythropoietin (EPO, n = 10, 6.8%) and nitric oxide (NO, n = 9, 6.2%), the objectives of the trial and follow-up were analyzed in more details. Although a matter of debate, the use of placebo should be promoted in neonates to evaluate a potential new treatment, in the absence of reference drug. Analysis of the trials evaluating steroids showed that long-term follow-up of exposed patients, although required by international guidelines, is frequently missing and should be planned to collect additional information and optimize drug evaluation in these high-risk patients.

  11. Randomized controlled trials in schizophrenia: opportunities, limitations, and trial design alternatives

    PubMed Central

    Correll, Christoph U.; Kishimoto, Taishiro; Kane, John M.

    2011-01-01

    State-of-the art clinical trial design and methodology are enormously important for the advancement of the field. In contrast, the critical relevance of trial conduct and implementation have only more recently been the focus of discussion and research. Although randomized controlled trials are generally considered the gold standard for the assessment of pharmacologic and nonpharmacologic interventions in medicine, trials are vulnerable to complications and influences that can seriously compromise their success, Like interventions, trial design and conduct are also contextual. They need to be individualized and adapted to a number of relevant variables, such as setting, population, illness phase, interventions, patient and rater expectations and biases, and the overall aims of the investigation. While this means that there is no unified approach possible, certain general principles and guidelines require careful consideration. Knowledge of basic solutions and alternatives, and the recognition of the complex challenges that need to be addressed proactively can help to minimize unwanted outcomes, including trial failure and uninformative or falsely negative outcomes. Moreover, novel design alternatives need to be explored that target sample enrichment according to the study question and enhancement of precision in the measurement of relevant outcomes. We propose two novel design strategies that take advantage of the recently validated early antipsychotic response paradigm (that has also been observed with antidepressants and mood stabilizers). In the “early responder randomized discontinuation design” all patients are assigned to the active drug, and only those who had at least a minimal response at 2 weeks are enrolled in a double-blind, placebo-controlled discontinuation trial, enriching the placebo controlled trial portion with true drug responders. In the mirror image “early nonresponder randomized dose increase or augmentation design,” early nonresponders

  12. Sample size in orthodontic randomized controlled trials: are numbers justified?

    PubMed

    Koletsi, Despina; Pandis, Nikolaos; Fleming, Padhraig S

    2014-02-01

    Sample size calculations are advocated by the Consolidated Standards of Reporting Trials (CONSORT) group to justify sample sizes in randomized controlled trials (RCTs). This study aimed to analyse the reporting of sample size calculations in trials published as RCTs in orthodontic speciality journals. The performance of sample size calculations was assessed and calculations verified where possible. Related aspects, including number of authors; parallel, split-mouth, or other design; single- or multi-centre study; region of publication; type of data analysis (intention-to-treat or per-protocol basis); and number of participants recruited and lost to follow-up, were considered. Of 139 RCTs identified, complete sample size calculations were reported in 41 studies (29.5 per cent). Parallel designs were typically adopted (n = 113; 81 per cent), with 80 per cent (n = 111) involving two arms and 16 per cent having three arms. Data analysis was conducted on an intention-to-treat (ITT) basis in a small minority of studies (n = 18; 13 per cent). According to the calculations presented, overall, a median of 46 participants were required to demonstrate sufficient power to highlight meaningful differences (typically at a power of 80 per cent). The median number of participants recruited was 60, with a median of 4 participants being lost to follow-up. Our finding indicates good agreement between projected numbers required and those verified (median discrepancy: 5.3 per cent), although only a minority of trials (29.5 per cent) could be examined. Although sample size calculations are often reported in trials published as RCTs in orthodontic speciality journals, presentation is suboptimal and in need of significant improvement.

  13. Subcuticular closure versus Dermabond: a prospective randomized trial.

    PubMed

    Switzer, Erin F; Dinsmore, Robert C; North, James H

    2003-05-01

    2-Octylcyanoacrylate tissue adhesive (Dermabond, Ethicon, Inc, Somerville, NJ) is being used successfully for closure of minor lacerations. To date, however, there have been no studies evaluating its use in the operating room for surgical incisions. We conducted a prospective randomized trial to compare the closure of inguinal herniorrhaphy incisions using 2-octylcyanoacrylate tissue adhesive (Dermabond) with closures using 4-0 Monocryl (Ethicon, Inc) in a running subcuticular closure. A total of 46 incisions were randomized at the time of closure. Of these incisions 24 were randomized to Dermabond closure (TA) and 22 were randomized to subcuticular closure (SC). Performance measures included: time for closure, wound complications, and cosmesis. Cosmesis was evaluated by blinded evaluation of photographs of the incisions taken 4 weeks after surgery. Closure times for the TA group were faster than in the SC group (mean of 155 vs 286 seconds; P < 0.001). Wound complications were higher in the TA group (P = 0.045). Cosmesis was also felt to be better in the SC group with a score of 4.2 versus 3.88, but this did not reach statistical significance. Although the use of Dermabond did result in faster wound cultures it also resulted in an increase in wound complications. The difference in mean cosmetic score for each group was not statistically significant but trended toward better scores in the SC group. Based on these findings we do not feel Dermabond is an acceptable alternative to subcuticular suture closure in inguinal herniorrhaphy incisions.

  14. Morning compared with evening induction of labor: a nested randomized controlled trial. A nested randomized controlled trial.

    PubMed

    Dodd, Jodie M; Crowther, Caroline A; Robinson, Jeffrey S

    2006-08-01

    To test the hypothesis that commencing induction of labor in the morning more closely reflects the physiologic timing of onset of labor and is associated with fewer women who remain undelivered 24 hours after cervical ripening and induction begins. This was a nested randomized clinical trial, conducted between April 2001 and December 2004. Pregnant women at more than 36+6 weeks gestation with a cephalic presentation who were scheduled for prostaglandin induction of labor were eligible to participate. Women were randomly assigned to either admission in the morning (0800 hours) or admission in the evening (2,000 hours). The primary outcome measures were vaginal birth not achieved in 24 hours, uterine hyperstimulation with associated fetal heart rate changes, and cesarean delivery. A total of 620 women were entered in the trial, with 280 women in the morning admission group and 340 women in the evening admission group. There were no statistically significant differences between the timing of admission for induction and the primary trial outcomes. However, women admitted in the morning were less likely to require oxytocin infusion (morning admission 126 of 280 [45.0%] compared with evening admission 184 of 340 [54.1%]; relative risk 0.83, 95% confidence interval 0.70-0.97; P=.022). Nulliparous women admitted in the morning were less likely to require operative vaginal birth (morning admission 10 of 62 [16.1%] compared with evening admission 28 of 82 [34.2%]; relative risk 0.47, 95% confidence interval 0.25-0.90; P=.015). For women who require induction of labor, consideration should be given to admission in the morning rather than admission in the evening. Australian Clinical Trials Registry, www.actr.org.au, 12606000156583.

  15. Impact of Length or Relevance of Questionnaires on Attrition in Online Trials: Randomized Controlled Trial

    PubMed Central

    Kalaitzaki, Eleftheria; White, Ian R; Khadjesari, Zarnie; Murray, Elizabeth; Linke, Stuart; Thompson, Simon G; Godfrey, Christine; Wallace, Paul

    2011-01-01

    Background There has been limited study of factors influencing response rates and attrition in online research. Online experiments were nested within the pilot (study 1, n = 3780) and main trial (study 2, n = 2667) phases of an evaluation of a Web-based intervention for hazardous drinkers: the Down Your Drink randomized controlled trial (DYD-RCT). Objectives The objective was to determine whether differences in the length and relevance of questionnaires can impact upon loss to follow-up in online trials. Methods A randomized controlled trial design was used. All participants who consented to enter DYD-RCT and completed the primary outcome questionnaires were randomized to complete one of four secondary outcome questionnaires at baseline and at follow-up. These questionnaires varied in length (additional 23 or 34 versus 10 items) and relevance (alcohol problems versus mental health). The outcome measure was the proportion of participants who completed follow-up at each of two follow-up intervals: study 1 after 1 and 3 months and study 2 after 3 and 12 months. Results At all four follow-up intervals there were no significant effects of additional questionnaire length on follow-up. Randomization to the less relevant questionnaire resulted in significantly lower rates of follow-up in two of the four assessments made (absolute difference of 4%, 95% confidence interval [CI] 0%-8%, in both study 1 after 1 month and in study 2 after 12 months). A post hoc pooled analysis across all four follow-up intervals found this effect of marginal statistical significance (unadjusted difference, 3%, range 1%-5%, P = .01; difference adjusted for prespecified covariates, 3%, range 0%-5%, P = .05). Conclusions Apparently minor differences in study design decisions may have a measurable impact on attrition in trials. Further investigation is warranted of the impact of the relevance of outcome measures on follow-up rates and, more broadly, of the consequences of what we ask participants to

  16. The Ethics of Randomized Controlled Trials in Social Settings: Can Social Trials Be Scientifically Promising and Must There Be Equipoise?

    ERIC Educational Resources Information Center

    Fives, Allyn; Russell, Daniel W.; Canavan, John; Lyons, Rena; Eaton, Patricia; Devaney, Carmel; Kearns, Norean; O'Brien, Aoife

    2015-01-01

    In a randomized controlled trial (RCT), treatments are assigned randomly and treatments are withheld from participants. Is it ethically permissible to conduct an RCT in a social setting? This paper addresses two conditions for justifying RCTs: that there should be a state of equipoise and that the trial should be scientifically promising.…

  17. The Ethics of Randomized Controlled Trials in Social Settings: Can Social Trials Be Scientifically Promising and Must There Be Equipoise?

    ERIC Educational Resources Information Center

    Fives, Allyn; Russell, Daniel W.; Canavan, John; Lyons, Rena; Eaton, Patricia; Devaney, Carmel; Kearns, Norean; O'Brien, Aoife

    2015-01-01

    In a randomized controlled trial (RCT), treatments are assigned randomly and treatments are withheld from participants. Is it ethically permissible to conduct an RCT in a social setting? This paper addresses two conditions for justifying RCTs: that there should be a state of equipoise and that the trial should be scientifically promising.…

  18. Fluoride concentration from dental sealants: a randomized clinical trial.

    PubMed

    Campus, G; Carta, G; Cagetti, M G; Bossù, M; Sale, S; Cocco, F; Conti, G; Nardone, M; Sanna, G; Strohmenger, L; Lingström, P

    2013-07-01

    A randomized clinical trial was performed in schoolchildren (6-7 yrs) to evaluate fluoride concentration in interproximal fluid after the placement of 3 different sealants. The sample consisted of 2,776 children randomly divided: 926 in the high-viscosity Glass-ionomer Cement group (GIC group), 923 in the fluoride Resin-based group (fluoride-RB group), and 927 in the no-fluoride Resin-based group (RB group). In total, 2,640 children completed the trial. Sealants were applied following manufacturer's instructions. Interproximal fluid samples were collected at baseline and 2, 7, and 21 days after application of sealants, by insertion of a standardized paperpoint into the interproximal mesial space of the sealed tooth for 15 seconds. Fluoride concentration was evaluated by means of a fluoride ion-selective electrode. At 2 days after sealant application, fluoride concentration was significantly higher in GIC and fluoride-RB groups compared with that in the RB group (p < .01). Mean fluoride concentrations after 7 days were 2.54 (SE 0.68) ppm, 0.85 (SE 0.26) ppm, and 0.53 (SE 0.11) ppm for the three groups, respectively. After 21 days, fluoride concentration in the GIC group remained higher than that in the other two groups. High-viscosity GIC sealants increased the fluoride concentrations in interproximal fluid more than did a Resin-based sealant containing fluoride.

  19. Reiki for the Treatment of Fibromyalgia: A Randomized Controlled Trial

    PubMed Central

    Assefi, Nassim; Bogart, Andy; Goldberg, Jack

    2008-01-01

    Abstract Objective Fibromyalgia is a common, chronic pain condition for which patients frequently use complementary and alternative medicine, including Reiki. Our objective was to determine whether Reiki is beneficial as an adjunctive fibromyalgia treatment. Design This was a factorial designed, randomized, sham-controlled trial in which participants, data collection staff, and data analysts were blinded to treatment group. Setting/location The study setting was private medical offices in the Seattle, Washington metropolitan area. Subjects The subjects were comprised 100 adults with fibromyalgia. Intervention Four (4) groups received twice-weekly treatment for 8 weeks by either a Reiki master or actor randomized to use direct touch or no touch (distant therapy). Outcome measures The primary outcome was subjective pain as measured by visual analog scale at weeks 4, 8, and 20 (3 months following end of treatment). Secondary outcomes were physical and mental functioning, medication use, and health provider visits. Participant blinding and adverse effects were ascertained by selfreport. Improvement between groups was examined in an intention-to-treat analysis. Results Neither Reiki nor touch had any effect on pain or any of the secondary outcomes. All outcome measures were nearly identical among the 4 treatment groups during the course of the trial. Conclusion Neither Reiki nor touch improved the symptoms of fibromyalgia. Energy medicine modalities such as Reiki should be rigorously studied before being recommended to patients with chronic pain symptoms. PMID:18991519

  20. Reiki for the treatment of fibromyalgia: a randomized controlled trial.

    PubMed

    Assefi, Nassim; Bogart, Andy; Goldberg, Jack; Buchwald, Dedra

    2008-11-01

    Fibromyalgia is a common, chronic pain condition for which patients frequently use complementary and alternative medicine, including Reiki. Our objective was to determine whether Reiki is beneficial as an adjunctive fibromyalgia treatment. This was a factorial designed, randomized, sham-controlled trial in which participants, data collection staff, and data analysts were blinded to treatment group. The study setting was private medical offices in the Seattle, Washington metropolitan area. The subjects were comprised 100 adults with fibromyalgia. Four (4) groups received twice-weekly treatment for 8 weeks by either a Reiki master or actor randomized to use direct touch or no touch (distant therapy). The primary outcome was subjective pain as measured by visual analog scale at weeks 4, 8, and 20 (3 months following end of treatment). Secondary outcomes were physical and mental functioning, medication use, and health provider visits. Participant blinding and adverse effects were ascertained by self-report. Improvement between groups was examined in an intention-to-treat analysis. Neither Reiki nor touch had any effect on pain or any of the secondary outcomes. All outcome measures were nearly identical among the 4 treatment groups during the course of the trial. Neither Reiki nor touch improved the symptoms of fibromyalgia. Energy medicine modalities such as Reiki should be rigorously studied before being recommended to patients with chronic pain symptoms.

  1. Antenatal hypnosis training and childbirth experience: a randomized controlled trial.

    PubMed

    Werner, Anette; Uldbjerg, Niels; Zachariae, Robert; Wu, Chun Sen; Nohr, Ellen A

    2013-12-01

    Childbirth is a demanding event in a woman's life. The aim of this study was to explore whether a brief intervention in the form of an antenatal course in self-hypnosis to ease childbirth could improve the childbirth experience. In a randomized, controlled, single-blinded trial, 1,222 healthy nulliparous women were allocated to one of three groups during pregnancy: A hypnosis group participating in three 1-hour sessions teaching self-hypnosis to ease childbirth, a relaxation group receiving three 1-hour lessons in various relaxation methods and Mindfulness, and a usual care group receiving ordinary antenatal care only. Wijmas Delivery Expectancy/Experience Questionnaire (W-DEQ) was used to measure the childbirth experience 6 weeks postpartum. The intention-to-treat analysis indicated that women in the hypnosis group experienced their childbirth as better compared with the other two groups (mean W-DEQ score of 42.9 in the Hypnosis group, 47.2 in the Relaxation group, and 47.5 in the Care as usual group (p = 0.01)). The tendency toward a better childbirth experience in the hypnosis group was also seen in subgroup analyses for mode of delivery and for levels of fear. In this large randomized controlled trial, a brief course in self-hypnosis improved the women's childbirth experience. © 2013, Copyright the Authors Journal compilation © 2013, Wiley Periodicals, Inc.

  2. 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

  3. Bibliometric analysis of the literature of randomized controlled trials

    PubMed Central

    Tsay, Ming-yueh; Yang, Yen-hsu

    2005-01-01

    Objective: Evidence-based medicine (EBM) is a significant issue and the randomized controlled trial (RCT) literature plays a fundamental role in developing EBM. This study investigates the features of RCT literature based on bibliometric methods. Growth of the literature, publication types, languages, publication countries, and research subjects are addressed. The distribution of journal articles was also examined utilizing Bradford's law and Bradford-Zipf's law. Method: The MEDLINE database was searched for articles indexed under the publication type “Randomized Control Trial,” and articles retrieved were counted and analyzed using Microsoft Access, Microsoft Excel, and PERL. Results: From 1990 to 2001, a total of 114,850 citations dealing with RCTs were retrieved. The literature growth rate, from 1965 to 2001, is steadily rising and follows an exponential model. Journal articles are the predominant form of publication, and the multicenter study is extensively used. English is the most commonly used language. Conclusions: Generally, RCTs are found in publications concentrating on cardiovascular disease, cancer, asthma, postoperative conditon, health, and anesthetics. Zone analysis and graphical formulation from Bradford's law of scattering shows variations from the standard Bradford model. Forty-two core journals were identified using Bradford's law. PMID:16239941

  4. A quality assessment of randomized clinical trials in pediatric orthopaedics.

    PubMed

    Dulai, Sukhdeep K; Slobogean, Bronwyn L T; Beauchamp, Richard D; Mulpuri, Kishore

    2007-01-01

    The promotion and practice of evidence-based medicine necessitates a critical evaluation of medical literature, including the criterion standard of randomized clinical trials (RCTs). Recent studies have examined the quality of RCTs in various surgical specialties, but no study has focused on pediatric orthopaedics. The purpose of this study was to assess and describe the quality of RCTs published in the last 10 years in journals with high clinical impact in pediatric orthopaedics. All of the RCTs in pediatric orthopaedics published in 5 well-recognized journals between 1995 and 2005 were reviewed using the Detsky Quality Assessment Scale. The mean percentage score on the Detsky scale was 53% (95% confidence interval, 46%-60%). Only 7 (19%) of the articles satisfied the threshold for a satisfactory level of methodological quality (Detsky >75%). Most RCTs in pediatric orthopaedics that are published in well-recognized peer-reviewed journals demonstrate substantial deficiencies in methodological quality. Particular areas of weakness include inadequate rigor and reporting of randomization methods, use of inappropriate or poorly described outcome measures, inadequate description of inclusion and exclusion criteria, and inappropriate statistical analysis. Further efforts are necessary to improve the conduct and reporting of clinical trials in this field to avoid inadvertent misinformation of the clinical community.

  5. Randomized trial on fluorides and sealants for fissure caries prevention.

    PubMed

    Liu, B Y; Lo, E C M; Chu, C H; Lin, H C

    2012-08-01

    To investigate the effectiveness of topical fluorides in preventing fissure caries, we conducted a randomized controlled trial with parallel groups. In total, 501 children (1,539 molars, 3,078 sites), mean age 9.1 years, who had at least one sound permanent first molar with deep fissures or fissures with signs of early caries were recruited. They were randomly allocated among four groups: (1) resin sealant, single placement; (2) 5% NaF varnish, semi-annual application; (3) 38% silver diamine fluoride (SDF) solution, annual application; and (4) placebo control. Follow-up examinations were conducted every 6 months by a masked examiner. After 24 months, 485 children (97%) were examined. Proportions of pit/fissure sites with dentin caries in the sealant, NaF, SDF, and control groups were 1.6%, 2.4%, 2.2%, and 4.6%, respectively. A multi-level logistic regression analysis accounting for the effects of data clustering and confounding factors showed that fissures in any of the three treatment groups had significantly lower risks of carious cavity development into dentin than did controls (p < 0.05). We concluded that placement of resin sealant, semi-annual application of NaF varnish, and annual application of SDF solution are all effective in preventing pit and fissure caries in permanent molars (ClinicalTrials.gov number CT01446107).

  6. Moving a Randomized Clinical Trial into an Observational Cohort

    PubMed Central

    Goodman, Phyllis J.; Hartline, Jo Ann; Tangen, Catherine M.; Crowley, John J.; Minasian, Lori M.; Klein, Eric A.; Cook, Elise D.; Darke, Amy K.; Arnold, Kathryn B.; Anderson, Karen; Yee, Monica; Meyskens, Frank L.; Baker, Laurence H.

    2013-01-01

    Background The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was a randomized, double blind, placebo-controlled prostate cancer prevention study funded by the National Cancer Institute and conducted by SWOG (Southwest Oncology Group). A total of 35,533 men were assigned randomly to one of four treatment groups (vitamin E + placebo, selenium + placebo, vitamin E + selenium, placebo + placebo. The independent Data and Safety Monitoring Committee recommended the discontinuation of study supplements because of the lack of efficacy for risk reduction and because futility analyses demonstrated no possibility of benefit of the supplements to the anticipated degree (25% reduction in prostate cancer incidence) with additional follow-up. Study leadership agreed that the randomized trial should be terminated but believed that the cohort should be maintained and followed as the additional follow-up would contribute important information to the understanding of the biologic consequences of the intervention. Since the participants no longer needed to be seen in person to assess acute toxicities or to be given study supplements, it was determined that the most efficient and cost-effective way to follow them was via a central coordinated effort. Purpose A number of changes were necessary at the local Study Sites and SELECT Statistical Center to transition to following participants via a Central Coordinating Center. We describe the transition process from a randomized clinical trial to the observational Centralized Follow-up (CFU) study. Methods The process of transitioning SELECT, implemented at more than 400 Study Sites across the United States, Canada and Puerto Rico, entailed many critical decisions and actions including updates to online documents such as the SELECT Workbench and Study Manual, a protocol amendment, reorganization of the Statistical Center, creation of a Transition Committee, development of materials for SELECT Study Sites, development of procedures

  7. Research in Nursing and Nutrition: Is Randomized Clinical Trial the Actual Gold Standard?

    PubMed

    Baldi, Ileana; Soriani, Nicola; Lorenzoni, Giulia; Azzolina, Danila; Dal Lago, Elisa; De Bardi, Sara; Verduci, Elvira; Zanotti, Renzo; Gregori, Dario

    The aim of this study was to assess the quality of reporting of nurse-driven randomized controlled trials involving a direct nutritional intervention. A bibliometric search for randomized controlled trials involving a direct nutritional intervention from 1991 to 2011 in nursing research was conducted. Both quality of the study and design aspects were evaluated. The prevalent randomized controlled trial design used is 2-arm parallel, individual, and randomized with a continuous primary endpoint. Global numbers of randomized controlled trials and the proportion of good-quality randomized controlled trials began a steady and marked rise, more than doubling, from the 1990s to about 2001 and increased slowly thereafter. Studies are overall sufficiently well designed, although there is still room for quality improvement. Additionally, implementation of new randomized controlled trial designs exists and should be advocated.

  8. Norfloxacin therapy for hepatopulmonary syndrome: a pilot randomized controlled trial.

    PubMed

    Gupta, Samir; Faughnan, Marie E; Lilly, Les; Hutchison, Stuart; Fowler, Robert; Bayoumi, Ahmed M

    2010-12-01

    The hepatopulmonary syndrome occurs in up to one-third of patients with cirrhosis. Animal models of this disease suggest that endotoxemia might cause nitric oxide-mediated vascular dilatation that can be inhibited by the antibiotic norfloxacin. We sought to test this hypothesis in humans. We conducted a pilot randomized, controlled crossover trial of norfloxacin 400 mg twice daily for 4 weeks with a 4-week washout period to assess the feasibility of a larger trial. The primary clinical end point was change in alveolar-arterial oxygen gradient (AaDO₂). Recruitment was challenging, and change in AaDO₂ was highly variable. We recruited 9 adults (1 woman; age, 60 ± 9 years; AaDO₂, 50 ± 22 mm Hg). AaDO₂ decreased by 0.8 ± 4.8 and 3.4 ± 12.4 mm Hg while on norfloxacin and placebo, respectively (P = .59). Recruitment difficulties and variability of the primary outcome measure suggest the need for a multicenter clinical research network for future therapeutic trials in this disease. There was no major effect of norfloxacin on gas exchange in patients with hepatopulmonary syndrome. Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

  9. Clinical impact of 8 prospective, randomized, multicenter glaucoma trials.

    PubMed

    Panarelli, Joseph F; Banitt, Michael R; Sidoti, Paul A; Budenz, Donald L; Singh, Kuldev

    2015-01-01

    To determine the impact of 8 multicenter randomized clinical trials (RCTs) on glaucoma practice. An electronic survey was distributed to the members of the American Glaucoma Society (AGS). Each participant was asked 2 study-specific questions and 1 standard question common to all 8 RCTs assessing the study's impact on clinical practice. RCTs included in the survey were the Advanced Glaucoma Intervention Study (AGIS), Collaborative Initial Glaucoma Treatment Study (CIGTS), Collaborative Normal Tension Glaucoma (CNTG) Study, European Glaucoma Prevention Study (EGPS), Early Manifest Glaucoma Trial (EMGT), Glaucoma Laser Trial (GLT), Ocular Hypertension Treatment Study (OHTS), and Tube Versus Trabeculectomy (TVT) Study. A 5-point Likert scale was used for rating all responses. The practice setting and duration of glaucoma practice was determined for all AGS members who responded. A total of 206 (23.0%) of 894 AGS members participated in the survey. Among those who responded, 46.4% were self classified as academic practitioners and 53.6% worked in a private practice setting. Mean Likert scores for the standard question evaluating the overall impact of the RCT were OHTS 4.47, CNTG Study 4.13, AGIS 3.78, TVT Study 3.53, EMGT 3.48, CIGTS 3.44, GLT 3.39, and 2.69 EGPS. Substantial differences were observed in the clinical impact of several RCTs in glaucoma. The reported impact of each study likely reflects several factors including study timing, design, conduct, and interpretation of results.

  10. Predicting analysis times in randomized clinical trials with cancer immunotherapy.

    PubMed

    Chen, Tai-Tsang

    2016-02-01

    A new class of immuno-oncology agents has recently been shown to induce long-term survival in a proportion of treated patients. This phenomenon poses unique challenges for the prediction of analysis time in event-driven studies. If the phenomenon of long-term survival is not accounted for properly, the accuracy of the prediction based on the existing methods may be substantially compromised. Parametric mixture cure rate models with the best fit to empirical clinical trial data were proposed to predict analysis times in immuno-oncology studies during the course of the study. The proposed prediction procedure also accounts for the mechanism of action introduced by cancer immunotherapies, such as delayed and long-term survival effects. The proposed methodology was retrospectively applied to a randomized phase III immuno-oncology clinical trial. Among various parametric mixture cure rate models, the Weibull cure rate model was found to be the best-fitting model for this study. The unique survival kinetics of cancer immunotherapy was captured in the longitudinal predictions of the final analysis times. Parametric mixture cure rate models, along with estimated long-term survival rates, probabilities of study incompletion, and expected statistical powers over time, provide immuno-oncology clinical trial researchers with a useful tool for continuous event monitoring and prediction of analysis times, such that informed decisions with quantifiable risks can be made for better resource and logistic planning.

  11. Cognitive Function in a Randomized Trial of Evolocumab.

    PubMed

    Giugliano, Robert P; Mach, François; Zavitz, Kenton; Kurtz, Christopher; Im, Kyungah; Kanevsky, Estella; Schneider, Jingjing; Wang, Huei; Keech, Anthony; Pedersen, Terje R; Sabatine, Marc S; Sever, Peter S; Robinson, Jennifer G; Honarpour, Narimon; Wasserman, Scott M; Ott, Brian R

    2017-08-17

    Background Findings from clinical trials of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors have led to concern that these drugs or the low levels of low-density lipoprotein (LDL) cholesterol that result from their use are associated with cognitive deficits. Methods In a subgroup of patients from a randomized, placebo-controlled trial of evolocumab added to statin therapy, we prospectively assessed cognitive function using the Cambridge Neuropsychological Test Automated Battery. The primary end point was the score on the spatial working memory strategy index of executive function (scores range from 4 to 28, with lower scores indicating a more efficient use of strategy and planning). Secondary end points were the scores for working memory (scores range from 0 to 279, with lower scores indicating fewer errors), episodic memory (scores range from 0 to 70, with lower scores indicating fewer errors), and psychomotor speed (scores range from 100 to 5100 msec, with faster times representing better performance). Assessments of cognitive function were performed at baseline, week 24, yearly, and at the end of the trial. The primary analysis was a noninferiority comparison of the mean change from baseline in the score on the spatial working memory strategy index of executive function between the patients who received evolocumab and those who received placebo; the noninferiority margin was set at 20% of the standard deviation of the score in the placebo group. Results A total of 1204 patients were followed for a median of 19 months; the mean (±SD) change from baseline over time in the raw score for the spatial working memory strategy index of executive function (primary end point) was -0.21±2.62 in the evolocumab group and -0.29±2.81 in the placebo group (P<0.001 for noninferiority; P=0.85 for superiority). There were no significant between-group differences in the secondary end points of scores for working memory (change in raw score, -0.52 in the

  12. Targeting Prodromal Alzheimer Disease With Avagacestat: A Randomized Clinical Trial.

    PubMed

    Coric, Vladimir; Salloway, Stephen; van Dyck, Christopher H; Dubois, Bruno; Andreasen, Niels; Brody, Mark; Curtis, Craig; Soininen, Hilkka; Thein, Stephen; Shiovitz, Thomas; Pilcher, Gary; Ferris, Steven; Colby, Susan; Kerselaers, Wendy; Dockens, Randy; Soares, Holly; Kaplita, Stephen; Luo, Feng; Pachai, Chahin; Bracoud, Luc; Mintun, Mark; Grill, Joshua D; Marek, Ken; Seibyl, John; Cedarbaum, Jesse M; Albright, Charles; Feldman, Howard H; Berman, Robert M

    2015-11-01

    Early identification of Alzheimer disease (AD) is important for clinical management and affords the opportunity to assess potential disease-modifying agents in clinical trials. To our knowledge, this is the first report of a randomized trial to prospectively enrich a study population with prodromal AD (PDAD) defined by cerebrospinal fluid (CSF) biomarker criteria and mild cognitive impairment (MCI) symptoms. To assess the safety of the γ-secretase inhibitor avagacestat in PDAD and to determine whether CSF biomarkers can identify this patient population prior to clinical diagnosis of dementia. A randomized, placebo-controlled phase 2 clinical trial with a parallel, untreated, nonrandomized observational cohort of CSF biomarker-negative participants was conducted May 26, 2009, to July 9, 2013, in a multicenter global population. Of 1358 outpatients screened, 263 met MCI and CSF biomarker criteria for randomization into the treatment phase. One hundred two observational cohort participants who met MCI criteria but were CSF biomarker-negative were observed during the same study period to evaluate biomarker assay sensitivity. Oral avagacestat or placebo daily. Safety and tolerability of avagacestat. Of the 263 participants in the treatment phase, 132 were randomized to avagacestat and 131 to placebo; an additional 102 participants were observed in an untreated observational cohort. Avagacestat was relatively well tolerated with low discontinuation rates (19.6%) at a dose of 50 mg/d, whereas the dose of 125 mg/d had higher discontinuation rates (43%), primarily attributable to gastrointestinal tract adverse events. Increases in nonmelanoma skin cancer and nonprogressive, reversible renal tubule effects were observed with avagacestat. Serious adverse event rates were higher with avagacestat (49 participants [37.1%]) vs placebo (31 [23.7%]), attributable to the higher incidence of nonmelanoma skin cancer. At 2 years, progression to dementia was more frequent in the PDAD

  13. A Randomized Controlled Trial of Caries Prevention in Dental Practice.

    PubMed

    Tickle, M; O'Neill, C; Donaldson, M; Birch, S; Noble, S; Killough, S; Murphy, L; Greer, M; Brodison, J; Verghis, R; Worthington, H V

    2017-07-01

    We conducted a parallel group randomized controlled trial of children initially aged 2 to 3 y who were caries free, to prevent the children becoming caries active over the subsequent 36 mo. The setting was 22 dental practices in Northern Ireland, and children were randomly assigned by a clinical trials unit (CTU) (using computer-generated random numbers, with allocation concealed from the dental practice until each child was recruited) to the intervention (22,600-ppm fluoride varnish, toothbrush, 50-mL tube of 1,450 ppm fluoride toothpaste, and standardized, evidence-based prevention advice) or advice-only control at 6-monthly intervals. The primary outcome measure was conversion from caries-free to caries-active states. Secondary outcome measures were number of decayed, missing, or filled teeth (dmfs) in caries-active children, number of episodes of pain, and number of extracted teeth. Adverse reactions were recorded. Calibrated external examiners, blinded to the child's study group, assessed the status of the children at baseline and after 3 y. In total, 1,248 children (624 randomized to each group) were recruited, and 1,096 (549 intervention, 547 control) were included in the final analyses. Eighty-seven percent of intervention and 86% of control children attended every 6-mo visit ( P = 0.77). A total of 187 (34%) in the intervention group converted to caries active compared to 213 (39%) in the control group (odds ratio, 0.81; 95% confidence interval, 0.64-1.04; P = 0.11). Mean dmfs of those with caries in the intervention group was 7.2 compared to 9.6 in the control group ( P = 0.007). There was no significant difference in the number of episodes of pain between groups ( P = 0.81) or in the number of teeth extracted in caries-active children ( P = 0.95). Ten children in the intervention group had adverse reactions of a minor nature. This well-conducted trial failed to demonstrate that the intervention kept children caries free, but there was evidence that once

  14. A randomized trial of bevacizumab for newly diagnosed glioblastoma.

    PubMed

    Gilbert, Mark R; Dignam, James J; Armstrong, Terri S; Wefel, Jeffrey S; Blumenthal, Deborah T; Vogelbaum, Michael A; Colman, Howard; Chakravarti, Arnab; Pugh, Stephanie; Won, Minhee; Jeraj, Robert; Brown, Paul D; Jaeckle, Kurt A; Schiff, David; Stieber, Volker W; Brachman, David G; Werner-Wasik, Maria; Tremont-Lukats, Ivo W; Sulman, Erik P; Aldape, Kenneth D; Curran, Walter J; Mehta, Minesh P

    2014-02-20

    Concurrent treatment with temozolomide and radiotherapy followed by maintenance temozolomide is the standard of care for patients with newly diagnosed glioblastoma. Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor A, is currently approved for recurrent glioblastoma. Whether the addition of bevacizumab would improve survival among patients with newly diagnosed glioblastoma is not known. In this randomized, double-blind, placebo-controlled trial, we treated adults who had centrally confirmed glioblastoma with radiotherapy (60 Gy) and daily temozolomide. Treatment with bevacizumab or placebo began during week 4 of radiotherapy and was continued for up to 12 cycles of maintenance chemotherapy. At disease progression, the assigned treatment was revealed, and bevacizumab therapy could be initiated or continued. The trial was designed to detect a 25% reduction in the risk of death and a 30% reduction in the risk of progression or death, the two coprimary end points, with the addition of bevacizumab. A total of 978 patients were registered, and 637 underwent randomization. There was no significant difference in the duration of overall survival between the bevacizumab group and the placebo group (median, 15.7 and 16.1 months, respectively; hazard ratio for death in the bevacizumab group, 1.13). Progression-free survival was longer in the bevacizumab group (10.7 months vs. 7.3 months; hazard ratio for progression or death, 0.79). There were modest increases in rates of hypertension, thromboembolic events, intestinal perforation, and neutropenia in the bevacizumab group. Over time, an increased symptom burden, a worse quality of life, and a decline in neurocognitive function were more frequent in the bevacizumab group. First-line use of bevacizumab did not improve overall survival in patients with newly diagnosed glioblastoma. Progression-free survival was prolonged but did not reach the prespecified improvement target. (Funded by the

  15. Dressing Wear Time after Breast Reconstruction: A Randomized Clinical Trial

    PubMed Central

    Paiva, Luiz Francisley; Fonseca, Fernando Elias Martins; Cabral, Isaías Vieira; Pinto, Natália Lana Larcher; Juliano, Yara

    2016-01-01

    Background The evidence to support dressing standards for breast surgery wounds is empiric and scarce. Objective This two-arm randomized clinical trial was designed to assess the effect of dressing wear time on surgical site infection (SSI) rates, skin colonization and patient perceptions. Methods A total of 200 breast cancer patients undergoing breast reconstruction were prospectively enrolled. Patients were randomly allocated to group I (dressing removed on the first postoperative day, n = 100) or group II (dressing removed on the sixth postoperative day, n = 100). SSIs were defined and classified according to criteria from the Centers for Disease Control and Prevention. Samples collected before placing the dressing and after 1 day (group I) and 6 days (both groups) were cultured for skin colonization assessments. Patients preferences and perceptions with regard to safety, comfort and convenience were recorded and analyzed. Results A total of 186 patients completed the follow-up. The global SSI rate was 4.5%. Six patients in group I and three in group II had SSI (p = 0.497). Before dressing, the groups were similar with regard to skin colonization. At the sixth day, there was a higher colonization by coagulase-negative staphylococci in group I (p<0.0001). Patients preferred to keep dressing for six days (p<0.0001), and considered this a safer choice (p<0.05). Conclusions Despite group I had a higher skin colonization by coagulase-negative staphylococci on the sixth postoperative day, there was no difference in SSI rates. Patients preferred keeping dressing for six days and considered it a safer choice. Trial Registration ClinicalTrials.gov NCT01148823 PMID:27911904

  16. Randomized Polypill Crossover Trial in People Aged 50 and Over

    PubMed Central

    Wald, David S.; Morris, Joan K.; Wald, Nicholas J.

    2012-01-01

    Background A Polypill is proposed for the primary prevention of cardiovascular disease in people judged to be at risk on account of their age alone. Its efficacy in reducing cholesterol and blood pressure is uncertain. Methods We conducted a randomized double-blind placebo-controlled crossover trial of a Polypill among individuals aged 50+ without a history of cardiovascular disease and compared the reductions with those predicted from published estimates of the effects of the individual drugs. Participants took the Polypill (amlodipine 2.5 mg, losartan 25 mg, hydrochlorothiazide 12.5 mg and simvastatin 40 mg) each evening for 12 weeks and a placebo each evening for 12 weeks in random sequence. The mean within-person differences in blood pressure and low density lipoprotein (LDL) cholesterol at the end of each 12 week period were determined. Results 84 out of 86 participants completed both treatment periods. The mean systolic blood pressure was reduced by 17.9 mmHg (95% CI, 15.7–20.1) on the Polypill, diastolic blood pressure by 9.8 mmHg (8.1–11.5), and LDL cholesterol by 1.4 mmol/L (1.2–1.6), reductions of 12%, 11%, and 39% respectively. The results were almost identical to those predicted; 18.4 mmHg, 9.7 mmHg, and 1.4 mmol/L respectively. Conclusion The Polypill resulted in the predicted reductions in blood pressure and LDL cholesterol. Long term reductions of this magnitude would have a substantial effect in preventing heart attacks and strokes. Trial Registration Controlled-Trials.com ISRCTN36672232 PMID:22815989

  17. Prospective, randomized trial of higher goal hemoglobin after subarachnoid hemorrhage.

    PubMed

    Naidech, Andrew M; Shaibani, Ali; Garg, Rajeev K; Duran, Isis M; Liebling, Storm M; Bassin, Sarice L; Bendok, Bernard R; Bernstein, Richard A; Batjer, H Hunt; Alberts, Mark J

    2010-12-01

    In patients with subarachnoid hemorrhage (SAH), higher hemoglobin (HGB) has been associated with better outcomes, but packed red blood cell (PRBC) transfusions with worse outcomes. We performed a prospective pilot trial of goal HGB after SAH. Forty-four patients with SAH and high risk for vasospasm were randomized to goal HGB concentration of at least 10 or 11.5 g/dl. We obtained blinded clinical outcomes at 14 days (NIH Stroke Scale and modified Rankin Scale, mRS), 28 days (mRS), and 3 months (mRS), and blinded interpretation of brain MRI for cerebral infarction at 14 days. This trial is registered at www.stroketrials.org. Forty-four patients were randomized. Patients with goal HGB 11.5 g/dl received more PRBC units per transfusion [1 (1-2) vs. 1 (1-1), P < 0.001] and more total PRBC units [3 (2-4) vs. 2 (1-3), P = 0.045]. Prospectively defined safety endpoints were not different between groups. HGB concentration was different between study groups from day 4 onwards. The number of cerebral infarctions on MRI (6 of 20 vs. 9 of 22), NIH Stroke Scale scores at 14 days [1 (0-9.75) vs. 2 (0-16)], and rates of independence on the mRS at 14 days (65% vs. 44%) and 28 days (80% vs. 67%) were similar, but favored higher goal HGB (P > 0.1 for all). Higher goal hemoglobin in patients with SAH seems to be safe and feasible. A phase III trial of goal HGB after SAH is warranted.

  18. Hockey Fans in Training: A Pilot Pragmatic Randomized Controlled Trial.

    PubMed

    Petrella, Robert J; Gill, Dawn P; Zou, Guangyong; De Cruz, Ashleigh; Riggin, Brendan; Bartol, Cassandra; Danylchuk, Karen; Hunt, Kate; Wyke, Sally; Gray, Cindy M; Bunn, Christopher; Zwarenstein, Merrick

    2017-07-17

    Hockey Fans in Training (Hockey FIT) is a gender-sensitized weight loss and healthy lifestyle program. We investigated: 1) feasibility of recruiting and retaining overweight and obese men into a pilot pragmatic randomized controlled trial; and 2) potential for Hockey FIT to lead to weight loss and improvements in other outcomes at 12 weeks and 12 months. Male fans of 2 ice hockey teams (35-65 years; body-mass index ≥28 kg/m) located in Ontario (Canada) were randomized to intervention (Hockey FIT) or comparator (Wait-list Control). Hockey FIT includes a 12-week active phase (weekly, coach-led group meetings including provision of dietary information, practice of behaviour change techniques, and safe exercise sessions plus incremental pedometer walking) and a 40-week minimally-supported phase (smartphone app for sustaining physical activity; private online social network; standardized emails; booster session/reunion). Measurement at baseline and 12 weeks (both groups), and 12 months (intervention group only), included clinical outcomes (e.g., weight) and self-reported physical activity, diet, self-rated health. Eighty men were recruited in 4 weeks; trial retention was >80% at 12 weeks and >75% at 12 months. At 12 weeks, the intervention group lost 3.6 (95% CI: -5.26, -1.90) kg more than the comparator (p<0.001) and maintained this weight loss to 12 months. The intervention group also demonstrated greater improvements in other clinical measures, physical activity, diet and self-rated health at 12 weeks; most sustained to 12 months. Results suggest feasible recruitment/retention of overweight and obese men in the Hockey FIT program. Results provide evidence for the potential effectiveness of Hockey FIT for weight loss and improved health in at-risk men and thus, evidence to proceed with a definitive trial.

  19. Acupuncture for posttraumatic stress disorder: a systematic review of randomized controlled trials and prospective clinical trials.

    PubMed

    Kim, Young-Dae; Heo, In; Shin, Byung-Cheul; Crawford, Cindy; Kang, Hyung-Won; Lim, Jung-Hwa

    2013-01-01

    To evaluate the current evidence for effectiveness of acupuncture for posttraumatic stress disorder (PTSD) in the form of a systematic review, a systematic literature search was conducted in 23 electronic databases. Grey literature was also searched. The key search terms were "acupuncture" and "PTSD." No language restrictions were imposed. We included all randomized or prospective clinical trials that evaluated acupuncture and its variants against a waitlist, sham acupuncture, conventional therapy control for PTSD, or without control. Four randomized controlled trials (RCTs) and 2 uncontrolled clinical trials (UCTs) out of 136 articles in total were systematically reviewed. One high-quality RCT reported that acupuncture was superior to waitlist control and therapeutic effects of acupuncture and cognitive-behavioral therapy (CBT) were similar based on the effect sizes. One RCT showed no statistical difference between acupuncture and selective serotonin reuptake inhibitors (SSRIs). One RCT reported a favorable effect of acupoint stimulation plus CBT against CBT alone. A meta-analysis of acupuncture plus moxibustion versus SSRI favored acupuncture plus moxibustion in three outcomes. This systematic review and meta-analysis suggest that the evidence of effectiveness of acupuncture for PTSD is encouraging but not cogent. Further qualified trials are needed to confirm whether acupuncture is effective for PTSD.

  20. Randomized controlled trials: who fails run-in?

    PubMed

    Rees, Judy R; Mott, Leila A; Barry, Elizabeth L; Baron, John A; Figueiredo, Jane C; Robertson, Douglas J; Bresalier, Robert S; Peacock, Janet L

    2016-07-29

    Early identification of participants at risk of run-in failure (RIF) may present opportunities to improve trial efficiency and generalizability. We conducted a partial factorial-design, randomized, controlled trial of calcium and vitamin D to prevent colorectal adenoma recurrence at 11 centers in the United States. At baseline, participants completed two self-administered questionnaires (SAQs) and a questionnaire administered by staff. Participants in the full factorial randomization (calcium, vitamin D, both, or neither) received a placebo during a 3-month single-blinded run-in; women electing to take calcium enrolled in a two-group randomization (calcium with vitamin D, or calcium alone) and received calcium during the run-in. Using logistic regression models, we examined baseline factors associated with RIF in three subgroups: men (N = 1606) and women (N = 301) in the full factorial randomization and women in the two-group randomization (N = 666). Overall, 314/2573 (12 %) participants failed run-in; 211 (67 %) took fewer than 80 % of their tablets (poor adherence), and 103 (33 %) withdrew or were uncooperative. In multivariable models, 8- to 13-fold variation was seen by study center in odds of RIF risk in the two largest groups. In men, RIF decreased with age (adjusted odds ratio [OR] per 5 years 0.85 [95 % confidence interval, CI; 0.76-0.96]) and was associated with being single (OR 1.65 [95 % CI; 1.10-2.47]), not graduating from high school (OR 2.77 [95 % CI; 1.58-4.85]), and missing SAQ data (OR 1.97 [1.40-2.76]). Among women, RIF was associated primarily with health-related factors; RIF risk was lower with higher physical health score (OR 0.73 [95 % CI; 0.62-0.86]) and baseline multivitamin use (OR 0.44 [95 % CI; 0.26-0.75]). Women in the 5-year colonoscopy surveillance interval were at greater risk of RIF than those with 3-year follow-up (OR 1.91 [95 % CI; 1.08-3.37]), and the number of prescription medicines taken was also

  1. The Sexunzipped Trial: Young People’s Views of Participating in an Online Randomized Controlled Trial

    PubMed Central

    Nicholas, Angela; Stevenson, Fiona; Murray, Elizabeth

    2013-01-01

    Background Incidence of sexually transmitted infections (STIs) among young people in the United Kingdom is increasing. The Internet can be a suitable medium for delivery of sexual health information and sexual health promotion, given its high usage among young people, its potential for creating a sense of anonymity, and ease of access. Online randomized controlled trials (RCTs) are increasingly being used to evaluate online interventions, but while there are many advantages to online methodologies, they can be associated with a number of problems, including poor engagement with online interventions, poor trial retention, and concerns about the validity of data collected through self-report online. We conducted an online feasibility trial that tested the effects of the Sexunzipped website for sexual health compared to an information-only website. This study reports on a qualitative evaluation of the trial procedures, describing participants’ experiences and views of the Sexunzipped online trial including methods of recruitment, incentives, methods of contact, and sexual health outcome measurement. Objective Our goal was to determine participants’ views of the acceptability and validity of the online trial methodology used in the pilot RCT of the Sexunzipped intervention. Methods We used three qualitative data sources to assess the acceptability and validity of the online pilot RCT methodology: (1) individual interviews with 22 participants from the pilot RCT, (2) 133 emails received by the trial coordinator from trial participants, and (3) 217 free-text comments from the baseline and follow-up questionnaires. Interviews were audio-recorded and transcribed verbatim. An iterative, thematic analysis of all three data sources was conducted to identify common themes related to the acceptability and feasibility of the online trial methodology. Results Interview participants found the trial design, including online recruitment via Facebook, online registration, email

  2. Laparoscopic versus open gastrectomy for gastric cancer, a multicenter prospectively randomized controlled trial (LOGICA-trial).

    PubMed

    Haverkamp, Leonie; Brenkman, Hylke J F; Seesing, Maarten F J; Gisbertz, Suzanne S; van Berge Henegouwen, Mark I; Luyer, Misha D P; Nieuwenhuijzen, Grard A P; Wijnhoven, Bas P L; van Lanschot, Jan J B; de Steur, Wobbe O; Hartgrink, Henk H; Stoot, Jan H M B; Hulsewé, Karel W E; Spillenaar Bilgen, Ernst J; Rütter, Jeroen E; Kouwenhoven, Ewout A; van Det, Marc J; van der Peet, Donald L; Daams, Freek; Draaisma, Werner A; Broeders, Ivo A M J; van Stel, Henk F; Lacle, Miangela M; Ruurda, Jelle P; van Hillegersberg, Richard

    2015-07-29

    For gastric cancer patients, surgical resection with en-bloc lymphadenectomy is the cornerstone of curative treatment. Open gastrectomy has long been the preferred surgical approach worldwide. However, this procedure is associated with considerable morbidity. Several meta-analyses have shown an advantage in short-term outcomes of laparoscopic gastrectomy compared to open procedures, with similar oncologic outcomes. However, it remains unclear whether the results of these Asian studies can be extrapolated to the Western population. In this trial from the Netherlands, patients with resectable gastric cancer will be randomized to laparoscopic or open gastrectomy. The study is a non-blinded, multicenter, prospectively randomized controlled superiority trial. Patients (≥18 years) with histologically proven, surgically resectable (cT1-4a, N0-3b, M0) gastric adenocarcinoma and European Clinical Oncology Group performance status 0, 1 or 2 are eligible to participate in the study after obtaining informed consent. Patients (n = 210) will be included in one of the ten participating Dutch centers and are randomized to either laparoscopic or open gastrectomy. The primary outcome is postoperative hospital stay (days). Secondary outcome parameters include postoperative morbidity and mortality, oncologic outcomes, readmissions, quality of life and cost-effectiveness. In this randomized controlled trial laparoscopic and open gastrectomy are compared in patients with resectable gastric cancer. It is expected that laparoscopic gastrectomy will result in a faster recovery of the patient and a shorter hospital stay. Secondly, it is expected that laparoscopic gastrectomy will be associated with a lower postoperative morbidity, less readmissions, higher cost-effectiveness, better postoperative quality of life, but with similar mortality and oncologic outcomes, compared to open gastrectomy. The study started on 1 December 2014. Inclusion and follow-up will take 3 and 5

  3. The Copenhagen Triage Algorithm: a randomized controlled trial.

    PubMed

    Hasselbalch, Rasmus Bo; Plesner, Louis Lind; Pries-Heje, Mia; Ravn, Lisbet; Lind, Morten; Greibe, Rasmus; Jensen, Birgitte Nybo; Rasmussen, Lars S; Iversen, Kasper

    2016-10-10

    Crowding in the emergency department (ED) is a well-known problem resulting in an increased risk of adverse outcomes. Effective triage might counteract this problem by identifying the sickest patients and ensuring early treatment. In the last two decades, systematic triage has become the standard in ED's worldwide. However, triage models are also time consuming, supported by limited evidence and could potentially be of more harm than benefit. The aim of this study is to develop a quicker triage model using data from a large cohort of unselected ED patients and evaluate if this new model is non-inferior to an existing triage model in a prospective randomized trial. The Copenhagen Triage Algorithm (CTA) study is a prospective two-center, cluster-randomized, cross-over, non-inferiority trial comparing CTA to the Danish Emergency Process Triage (DEPT). We include patients ≥16 years (n = 50.000) admitted to the ED in two large acute hospitals. Centers are randomly assigned to perform either CTA or DEPT triage first and then use the other triage model in the last time period. The CTA stratifies patients into 5 acuity levels in two steps. First, a scoring chart based on vital values is used to classify patients in an immediate category. Second, a clinical assessment by the ED nurse can alter the result suggested by the score up to two categories up or one down. The primary end-point is 30-day mortality and secondary end-points are length of stay, time to treatment, admission to intensive care unit, and readmission within 30 days. If proven non-inferior to standard DEPT triage, CTA will be a faster and simpler triage model that is still able to detect the critically ill. Simplifying triage will lessen the burden for the ED staff and possibly allow faster treatment. Clinicaltrials.gov: NCT02698319 , registered 24. of February 2016, retrospectively registered.

  4. A randomized trial of doxycycline for Mansonella perstans infection.

    PubMed

    Coulibaly, Yaya I; Dembele, Benoit; Diallo, Abdallah A; Lipner, Ettie M; Doumbia, Salif S; Coulibaly, Siaka Y; Konate, Siaka; Diallo, Dapa A; Yalcouye, Daniel; Kubofcik, Joseph; Doumbo, Ogobara K; Traore, Abdel K; Keita, Adama D; Fay, Michael P; Traore, Sekou F; Nutman, Thomas B; Klion, Amy D

    2009-10-08

    Mansonella perstans infection is common in areas of Africa where Wuchereria bancrofti, a causative agent of lymphatic filariasis, is endemic. M. perstans is refractory to standard antifilarial therapies. The recent discovery of bacterial endosymbionts (e.g., wolbachia) in most filarial species, including M. perstans, provides new therapeutic options for reducing microfilaremia. In an open-label, randomized trial, we recruited subjects with M. perstans microfilaremia, with or without concomitant W. bancrofti infection, from four villages in Mali and randomly assigned them to receive doxycycline, at a dose of 200 mg daily for 6 weeks (106 subjects), or no treatment (110). At 6 months, subjects who were coinfected with W. bancrofti underwent a second random assignment, to treatment with a single dose of albendazole (400 mg) and ivermectin (150 microg per kilogram of body weight) or no treatment. Subjects were monitored daily during the first 6-week study period for adverse events. M. perstans and W. bancrofti microfilarial levels were assessed at 6, 12, and 36 months. At 12 months, 67 of 69 subjects who had received treatment with doxycycline only (97%) had no detectable M. perstans microfilariae per 60 microl of blood, as compared with 10 of 63 subjects who had received no treatment (16%) (relative risk, 6.18; 95% confidence interval, 3.63 to 11.89; P<0.001). At 36 months, M. perstans microfilaremia remained suppressed in 48 of 64 subjects who had received treatment with doxycycline only (75%), a finding that was consistent with a macrofilaricidal effect of doxycycline. Vomiting was more frequent in the doxycycline-treated group than in the untreated group (17% vs. 4%). These results are consistent with previous findings that M. perstans harbors the intracellular endosymbiont, wolbachia, and suggest that doxycycline is an effective therapy for M. perstans infection. (ClinicalTrials.gov number, NCT00340691.) 2009 Massachusetts Medical Society

  5. A Randomized Controlled Trial of Mentoring Interventions for Underrepresented Minorities.

    PubMed

    Lewis, Vivian; Martina, Camille A; McDermott, Michael P; Trief, Paula M; Goodman, Steven R; Morse, Gene D; LaGuardia, Jennifer G; Sharp, Daryl; Ryan, Richard M

    2016-07-01

    To conduct a randomized controlled trial to evaluate the effects of different mentoring interventions on the basic psychological need satisfaction of underrepresented minorities and women in academia. Participants were 150 mentor/protégé dyads from three academic medical centers and eight other colleges and universities in western and central New York, randomized from 2010 to 2013 into mentor training (using principles of self-determination theory); peer mentoring for protégés; mentor training and peer mentoring for protégés combined; or control/usual practice. Protégé participants were graduate students, fellows, and junior faculty who were from underrepresented groups based on race, ethnicity, gender, or disability.The primary analysis was a comparison of intervention effects on changes in protégés' satisfaction of their basic psychological needs (competence, autonomy, and relatedness) with their mentor. They completed a well-validated, online questionnaire every two months for one year. There was no significant effect at the end of one year of either mentor training or peer mentoring on protégés' psychological basic need satisfaction with mentor specifically or at work in general. Exploratory analyses showed a significant effect of the mentor-based intervention on the protégés' overall psychological need satisfaction with their mentor at two months, the time point closest to completing mentor training. This randomized controlled trial showed a potential short-term effect of mentor training on changing basic psychological need satisfaction of underrepresented scholars with their mentors. Despite the lack of sustained effect of either mentor training or peer mentoring, these short-term changes suggest feasibility and potential for future study.

  6. Sun Protection at Elementary Schools: A Cluster Randomized Trial

    PubMed Central

    Hunter, Seft; Love-Jackson, Kymia; Abdulla, Rania; Zhu, Weiwei; Lee, Ji-Hyun; Wells, Kristen J.

    2010-01-01

    Background Elementary schools represent both a source of childhood sun exposure and a setting for educational interventions. Methods Sun Protection of Florida's Children was a cluster randomized trial promoting hat use at (primary outcome) and outside of schools among fourth-grade students during August 8, 2006, through May 22, 2007. Twenty-two schools were randomly assigned to the intervention (1115 students) or control group (1376 students). Intervention schools received classroom sessions targeting sun protection attitudes and social norms. Each student attending an intervention school received two free wide-brimmed hats. Hat use at school was measured by direct observation and hat use outside of school was measured by self-report. A subgroup of 378 students (178 in the intervention group and 200 in the control group) underwent serial measurements of skin pigmentation to explore potential physiological effects of the intervention. Generalized linear mixed models were used to evaluate the intervention effect by accounting for the cluster randomized trial design. All P values were two-sided and were claimed as statistically significant at a level of .05. Results The percentage of students observed wearing hats at control schools remained essentially unchanged during the school year (baseline = 2%, fall = 0%, and spring = 1%) but increased statistically significantly at intervention schools (baseline = 2%, fall = 30%, and spring = 41%) (P < .001 for intervention effect comparing the change in rate of hat use over time at intervention vs control schools). Self-reported use of hats outside of school did not change statistically significantly during the study (control: baseline = 14%, fall = 14%, and spring = 11%; intervention: baseline = 24%, fall = 24%, and spring = 23%) nor did measures of skin pigmentation. Conclusions The intervention increased use of hats among fourth-grade students at school but had no effect on self-reported wide-brimmed hat use outside of

  7. Sunscreen and prevention of skin aging: a randomized trial.

    PubMed

    Hughes, Maria Celia B; Williams, Gail M; Baker, Peter; Green, Adèle C

    2013-06-04

    Sunscreen use and dietary antioxidants are advocated as preventives of skin aging, but supporting evidence is lacking. To determine whether regular use of sunscreen compared with discretionary use or β-carotene supplements compared with placebo retard skin aging, measured by degree of photoaging. Randomized, controlled, community-based intervention. (Australian New Zealand Clinical Trials Registry: ACTRN12610000086066). Nambour, Australia (latitude 26° S). 903 adults younger than 55 years out of 1621 adults randomly selected from a community register. Random assignment into 4 groups: daily use of broad-spectrum sunscreen and 30 mg of β-carotene, daily use of sunscreen and placebo, discretionary use of sunscreen and 30 mg of β-carotene, and discretionary use of sunscreen and placebo. Change in microtopography between 1992 and 1996 in the sunscreen and β-carotene groups compared with controls, graded by assessors blinded to treatment allocation. The daily sunscreen group showed no detectable increase in skin aging after 4.5 years. Skin aging from baseline to the end of the trial was 24% less in the daily sunscreen group than in the discretionary sunscreen group (relative odds, 0.76 [95% CI, 0.59 to 0.98]). β-Carotene supplementation had no overall effect on skin aging, although contrasting associations were seen in subgroups with different severity of aging at baseline. Some outcome data were missing, and power to detect moderate treatment effects was modest. Regular sunscreen use retards skin aging in healthy, middle-aged men and women. No overall effect of β-carotene on skin aging was identified, and further study is required to definitively exclude potential benefit or potential harm. National Health and Medical Research Council of Australia.

  8. Targeting Functional Decline in Alzheimer Disease: A Randomized Trial.

    PubMed

    Callahan, Christopher M; Boustani, Malaz A; Schmid, Arlene A; LaMantia, Michael A; Austrom, Mary G; Miller, Douglas K; Gao, Sujuan; Ferguson, Denisha Y; Lane, Kathleen A; Hendrie, Hugh C

    2017-02-07

    Alzheimer disease results in progressive functional decline, leading to loss of independence. To determine whether collaborative care plus 2 years of home-based occupational therapy delays functional decline. Randomized, controlled clinical trial. (ClinicalTrials.gov: NCT01314950). Urban public health system. 180 community-dwelling participants with Alzheimer disease and their informal caregivers. All participants received collaborative care for dementia. Patients in the intervention group also received in-home occupational therapy delivered in 24 sessions over 2 years. The primary outcome measure was the Alzheimer's Disease Cooperative Study Group Activities of Daily Living Scale (ADCS ADL); performance-based measures included the Short Physical Performance Battery (SPPB) and Short Portable Sarcopenia Measure (SPSM). At baseline, clinical characteristics did not differ significantly between groups; the mean Mini-Mental State Examination score for both groups was 19 (SD, 7). The intervention group received a median of 18 home visits from the study occupational therapists. In both groups, ADCS ADL scores declined over 24 months. At the primary end point of 24 months, ADCS ADL scores did not differ between groups (mean difference, 2.34 [95% CI, -5.27 to 9.96]). We also could not definitively demonstrate between-group differences in mean SPPB or SPSM values. The results of this trial are indeterminate and do not rule out potential clinically important effects of the intervention. The authors could not definitively demonstrate whether the addition of 2 years of in-home occupational therapy to a collaborative care management model slowed the rate of functional decline among persons with Alzheimer disease. This trial underscores the burden undertaken by caregivers as they provide care for family members with Alzheimer disease and the difficulty in slowing functional decline. National Institute on Aging.

  9. Randomized Trial of Reduced-Nicotine Standards for Cigarettes.

    PubMed

    Donny, Eric C; Denlinger, Rachel L; Tidey, Jennifer W; Koopmeiners, Joseph S; Benowitz, Neal L; Vandrey, Ryan G; al'Absi, Mustafa; Carmella, Steven G; Cinciripini, Paul M; Dermody, Sarah S; Drobes, David J; Hecht, Stephen S; Jensen, Joni; Lane, Tonya; Le, Chap T; McClernon, F Joseph; Montoya, Ivan D; Murphy, Sharon E; Robinson, Jason D; Stitzer, Maxine L; Strasser, Andrew A; Tindle, Hilary; Hatsukami, Dorothy K

    2015-10-01

    The Food and Drug Administration can set standards that reduce the nicotine content of cigarettes. We conducted a double-blind, parallel, randomized clinical trial between June 2013 and July 2014 at 10 sites. Eligibility criteria included an age of 18 years or older, smoking of five or more cigarettes per day, and no current interest in quitting smoking. Participants were randomly assigned to smoke for 6 weeks either their usual brand of cigarettes or one of six types of investigational cigarettes, provided free. The investigational cigarettes had nicotine content ranging from 15.8 mg per gram of tobacco (typical of commercial brands) to 0.4 mg per gram. The primary outcome was the number of cigarettes smoked per day during week 6. A total of 840 participants underwent randomization, and 780 completed the 6-week study. During week 6, the average number of cigarettes smoked per day was lower for participants randomly assigned to cigarettes containing 2.4, 1.3, or 0.4 mg of nicotine per gram of tobacco (16.5, 16.3, and 14.9 cigarettes, respectively) than for participants randomly assigned to their usual brand or to cigarettes containing 15.8 mg per gram (22.2 and 21.3 cigarettes, respectively; P<0.001). Participants assigned to cigarettes with 5.2 mg per gram smoked an average of 20.8 cigarettes per day, which did not differ significantly from the average number among those who smoked control cigarettes. Cigarettes with lower nicotine content, as compared with control cigarettes, reduced exposure to and dependence on nicotine, as well as craving during abstinence from smoking, without significantly increasing the expired carbon monoxide level or total puff volume, suggesting minimal compensation. Adverse events were generally mild and similar among groups. In this 6-week study, reduced-nicotine cigarettes versus standard-nicotine cigarettes reduced nicotine exposure and dependence and the number of cigarettes smoked. (Funded by the National Institute on Drug Abuse

  10. Randomized Trial of Reduced-Nicotine Standards for Cigarettes

    PubMed Central

    Donny, Eric C.; Denlinger, Rachel L.; Tidey, Jennifer W.; Koopmeiners, Joseph S.; Benowitz, Neal L.; Vandrey, Ryan G.; al’Absi, Mustafa; Carmella, Steven G.; Cinciripini, Paul M.; Dermody, Sarah S.; Drobes, David J.; Hecht, Stephen S.; Jensen, Joni; Lane, Tonya; Le, Chap T.; McClernon, F. Joseph; Montoya, Ivan D.; Murphy, Sharon E.; Robinson, Jason D.; Stitzer, Maxine L.; Strasser, Andrew A.; Tindle, Hilary; Hatsukami, Dorothy K.

    2015-01-01

    BACKGROUND The Food and Drug Administration can set standards that reduce the nicotine content of cigarettes. METHODS We conducted a double-blind, parallel, randomized clinical trial between June 2013 and July 2014 at 10 sites. Eligibility criteria included an age of 18 years or older, smoking of five or more cigarettes per day, and no current interest in quitting smoking. Participants were randomly assigned to smoke for 6 weeks either their usual brand of cigarettes or one of six types of investigational cigarettes, provided free. The investigational cigarettes had nicotine content ranging from 15.8 mg per gram of tobacco (typical of commercial brands) to 0.4 mg per gram. The primary outcome was the number of cigarettes smoked per day during week 6. RESULTS A total of 840 participants underwent randomization, and 780 completed the 6-week study. During week 6, the average number of cigarettes smoked per day was lower for participants randomly assigned to cigarettes containing 2.4, 1.3, or 0.4 mg of nicotine per gram of tobacco (16.5, 16.3, and 14.9 cigarettes, respectively) than for participants randomly assigned to their usual brand or to cigarettes containing 15.8 mg per gram (22.2 and 21.3 cigarettes, respectively; P<0.001). Participants assigned to cigarettes with 5.2 mg per gram smoked an average of 20.8 cigarettes per day, which did not differ significantly from the average number among those who smoked control cigarettes. Cigarettes with lower nicotine content, as compared with control cigarettes, reduced exposure to and dependence on nicotine, as well as craving during abstinence from smoking, without significantly increasing the expired carbon monoxide level or total puff volume, suggesting minimal compensation. Adverse events were generally mild and similar among groups. CONCLUSIONS In this 6-week study, reduced-nicotine cigarettes versus standard-nicotine cigarettes reduced nicotine exposure and dependence and the number of cigarettes smoked. (Funded by

  11. Randomized trial of achieving healthy lifestyles in psychiatric rehabilitation: the ACHIEVE trial

    PubMed Central

    2010-01-01

    Background Overweight and obesity are highly prevalent among persons with serious mental illness. These conditions likely contribute to premature cardiovascular disease and a 20 to 30 percent shortened life expectancy in this vulnerable population. Persons with serious mental illness need effective, appropriately tailored behavioral interventions to achieve and maintain weight loss. Psychiatric rehabilitation day programs provide logical intervention settings because mental health consumers often attend regularly and exercise can take place on-site. This paper describes the Randomized Trial of Achieving Healthy Lifestyles in Psychiatric Rehabilitation (ACHIEVE). The goal of the study is to determine the effectiveness of a behavioral weight loss intervention among persons with serious mental illness that attend psychiatric rehabilitation programs. Participants randomized to the intervention arm of the study are hypothesized to have greater weight loss than the control group. Methods/Design A targeted 320 men and women with serious mental illness and overweight or obesity (body mass index ≥ 25.0 kg/m2) will be recruited from 10 psychiatric rehabilitation programs across Maryland. The core design is a randomized, two-arm, parallel, multi-site clinical trial to compare the effectiveness of an 18-month behavioral weight loss intervention to usual care. Active intervention participants receive weight management sessions and physical activity classes on-site led by study interventionists. The intervention incorporates cognitive adaptations for persons with serious mental illness attending psychiatric rehabilitation programs. The initial intensive intervention period is six months, followed by a twelve-month maintenance period in which trained rehabilitation program staff assume responsibility for delivering parts of the intervention. Primary outcomes are weight loss at six and 18 months. Discussion Evidence-based approaches to the high burden of obesity and

  12. Impact of length or relevance of questionnaires on attrition in online trials: randomized controlled trial.

    PubMed

    McCambridge, Jim; Kalaitzaki, Eleftheria; White, Ian R; Khadjesari, Zarnie; Murray, Elizabeth; Linke, Stuart; Thompson, Simon G; Godfrey, Christine; Wallace, Paul

    2011-11-18

    There has been limited study of factors influencing response rates and attrition in online research. Online experiments were nested within the pilot (study 1, n = 3780) and main trial (study 2, n = 2667) phases of an evaluation of a Web-based intervention for hazardous drinkers: the Down Your Drink randomized controlled trial (DYD-RCT). The objective was to determine whether differences in the length and relevance of questionnaires can impact upon loss to follow-up in online trials. A randomized controlled trial design was used. All participants who consented to enter DYD-RCT and completed the primary outcome questionnaires were randomized to complete one of four secondary outcome questionnaires at baseline and at follow-up. These questionnaires varied in length (additional 23 or 34 versus 10 items) and relevance (alcohol problems versus mental health). The outcome measure was the proportion of participants who completed follow-up at each of two follow-up intervals: study 1 after 1 and 3 months and study 2 after 3 and 12 months. At all four follow-up intervals there were no significant effects of additional questionnaire length on follow-up. Randomization to the less relevant questionnaire resulted in significantly lower rates of follow-up in two of the four assessments made (absolute difference of 4%, 95% confidence interval [CI] 0%-8%, in both study 1 after 1 month and in study 2 after 12 months). A post hoc pooled analysis across all four follow-up intervals found this effect of marginal statistical significance (unadjusted difference, 3%, range 1%-5%, P = .01; difference adjusted for prespecified covariates, 3%, range 0%-5%, P = .05). Apparently minor differences in study design decisions may have a measurable impact on attrition in trials. Further investigation is warranted of the impact of the relevance of outcome measures on follow-up rates and, more broadly, of the consequences of what we ask participants to do when we invite them to take part in research

  13. Medication reconciliation at patient admission: a randomized controlled trial

    PubMed Central

    Mendes, Antonio E.; Lombardi, Natália F.; Andrzejevski, Vânia S.; Frandoloso, Gibran; Correr, Cassyano J.; Carvalho, Mauricio

    2015-01-01

    Objective: To measure length of hospital stay (LHS) in patients receiving medication reconciliation. Secondary characteristics included analysis of number of preadmission medications, medications prescribed at admission, number of discrepancies, and pharmacists interventions done and accepted by the attending physician. Methods: A 6 month, randomized, controlled trial conducted at a public teaching hospital in southern Brazil. Patients admitted to general wards were randomized to receive usual care or medication reconciliation, performed within the first 72 hours of hospital admission. Results: The randomization process assigned 68 patients to UC and 65 to MR. LHS was 10±15 days in usual care and 9±16 days in medication reconciliation (p=0.620). The total number of discrepancies was 327 in the medication reconciliation group, comprising 52.6% of unintentional discrepancies. Physicians accepted approximately 75.0% of the interventions. Conclusion: These results highlight weakness at patient transition care levels in a public teaching hospital. LHS, the primary outcome, should be further investigated in larger studies. Medication reconciliation was well accepted by physicians and it is a useful tool to find and correct discrepancies, minimizing the risk of adverse drug events and improving patient safety. PMID:27011775

  14. Acupuncture for Vascular Dementia: A Pragmatic Randomized Clinical Trial

    PubMed Central

    Shi, Guang-Xia; Li, Qian-Qian; Yang, Bo-Feng; Liu, Yan; Guan, Li-Ping; Wu, Meng-Meng; Wang, Lin-Peng; Liu, Cun-Zhi

    2015-01-01

    In this trial, patients who agreed to random assignment were allocated to a randomized acupuncture group (R-acupuncture group) or control group. Those who declined randomization were assigned to a nonrandomized acupuncture group (NR-acupuncture group). Patients in the R-acupuncture group and NR-acupuncture group received up to 21 acupuncture sessions during a period of 6 weeks plus routine care, while the control group received routine care alone. Cognitive function, activities of daily living, and quality of life were assessed by mini-mental state examination (MMSE), Activities of Daily Living Scale (ADL), and dementia quality of life questionnaire (DEMQOL), respectively. All the data were collected at baseline, after 6-week treatment, and after 4-week follow-up. No significant differences of MMSE scores were observed among the three groups but pooled-acupuncture group had significant higher score than control group. Compared to control group, ADL score significantly decreased in NR-acupuncture group and pooled-acupuncture group. For DEMQOL scores, no significant differences were observed among the three groups, as well as between pooled-acupuncture group and control group. Additional acupuncture to routine care may have beneficial effects on the improvements of cognitive status and activities of daily living but have limited efficacy on health-related quality of life in VaD patients. PMID:26495416

  15. How well are randomized controlled trials reported in the dermatology literature?

    PubMed

    Adetugbo, K; Williams, H

    2000-03-01

    To assess the methodological quality of the design and reporting of randomized controlled trials published in one major dermatology specialty journal. In a survey of all published parallel group randomized controlled trials, we found 73 reports with allocation described as randomized from all issues of Clinical and Experimental Dermatology from its inception in 1976 through 1997. Direct and indirect measures of the adequacy of randomization, trial sample size, baseline comparisons, and intention-to-treat analysis. Hand searching identified 73 randomized controlled trials, but only 31 of these were found by searching MEDLINE for the publication type clinical trials. Of the 73 randomized controlled trials, 68 contained sufficient information to include in the analysis. Only 1 study (1%) reported the method of random sequence generation, and only 5 studies (7%) reported adequate concealment of allocation. Among 38 trials that used simple randomization, the sample sizes in the comparison groups were identical in 22 occasions, raising the possibility that simple randomization might not have been adequately generated or concealed. Most trials (88%) excluded some randomized participants from their analysis. The median sample size was 23 per trial. Only 1 trial reported sample size and statistical power considerations and had an a priori main hypothesis. Hand searching is important for locating all relevant trials. There is the need for higher methodological quality in clinical trial reporting in dermatology journals. The adoption of the CONSORT (Consolidated Standards of Reporting Trials) statement and checklist for the reporting of trials should enhance the validity of and strengthen the evidence from clinical trials reports.

  16. The pursuit of balance: An overview of covariate-adaptive randomization techniques in clinical trials.

    PubMed

    Lin, Yunzhi; Zhu, Ming; Su, Zheng

    2015-11-01

    Randomization is fundamental to the design and conduct of clinical trials. Simple randomization ensures independence among subject treatment assignments and prevents potential selection biases, yet it does not guarantee balance in covariate distributions across treatment groups. Ensuring balance in important prognostic covariates across treatment groups is desirable for many reasons. A broad class of randomization methods for achieving balance are reviewed in this paper; these include block randomization, stratified randomization, minimization, and dynamic hierarchical randomization. Practical considerations arising from experience with using the techniques are described. A review of randomization methods used in practice in recent randomized clinical trials is also provided.

  17. Competing events and costs of clinical trials: Analysis of a randomized trial in prostate cancer.

    PubMed

    Zakeri, Kaveh; Rose, Brent S; D'Amico, Anthony V; Jeong, Jong-Hyeon; Mell, Loren K

    2015-04-01

    Clinical trial costs may be reduced by identifying enriched subpopulations of patients with favorable risk profiles for the events of interest. However, increased selectivity affects accrual rates, with uncertain impact on clinical trial cost. We conducted a secondary analysis of Southwest Oncology Group (SWOG) 8794 randomized trial of adjuvant radiotherapy for high-risk prostate cancer. The primary endpoint was metastasis-free survival (MFS), defined as time to metastasis or death from any cause (competing mortality). We used competing risks regression models to identify an enriched subgroup at high risk for metastasis and low risk for competing mortality. We applied a cost model to estimate the impact of enrichment on trial cost and duration. The treatment effect on metastasis was similar in the enriched subgroup (HR, 0.42; 95% CI, 0.23-0.76) compared to the whole cohort (HR, 0.50; 95% CI, 0.30-0.81) while the effect on competing mortality was not significant in the subgroup or the whole cohort (HR 0.70; 95% CI 0.39-1.23, vs. HR 0.94; 95% CI, 0.68-1.31). Due to the higher incidence of metastasis relative to competing mortality in the enriched subgroup, the treatment effect on MFS was greater in the subgroup compared to the whole cohort (HR 0.55; 95% CI 0.36-0.82, vs. HR 0.77; 95% CI, 0.58-1.01). Trial cost was 75% less in the subgroup compared to the whole cohort ($1.7 million vs. $6.8 million), and the trial duration was 30% shorter (8.4 vs. 12.0 years). Competing event enrichment can reduce clinical trial cost and duration, without sacrificing generalizability. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. The Sexunzipped Trial: Optimizing the Design of Online Randomized Controlled Trials

    PubMed Central

    Pavlou, Menelaos; Copas, Andrew; McCarthy, Ona; Carswell, Ken; Rait, Greta; Hart, Graham; Nazareth, Irwin; Free, Caroline; French, Rebecca; Murray, Elizabeth

    2013-01-01

    Background Sexual health problems such as unwanted pregnancy and sexually transmitted infection are important public health concerns and there is huge potential for health promotion using digital interventions. Evaluations of digital interventions are increasingly conducted online. Trial administration and data collection online offers many advantages, but concerns remain over fraudulent registration to obtain compensation, the quality of self-reported data, and high attrition. Objective This study addresses the feasibility of several dimensions of online trial design—recruitment, online consent, participant identity verification, randomization and concealment of allocation, online data collection, data quality, and retention at 3-month follow-up. Methods Young people aged 16 to 20 years and resident in the United Kingdom were recruited to the “Sexunzipped” online trial between November 2010 and March 2011 (n=2036). Participants filled in baseline demographic and sexual health questionnaires online and were randomized to the Sexunzipped interactive intervention website or to an information-only control website. Participants were also randomly allocated to a postal request (or no request) for a urine sample for genital chlamydia testing and receipt of a lower (£10/US$16) or higher (£20/US$32) value shopping voucher compensation for 3-month outcome data. Results The majority of the 2006 valid participants (90.98%, 1825/2006) were aged between 18 and 20 years at enrolment, from all four countries in the United Kingdom. Most were white (89.98%, 1805/2006), most were in school or training (77.48%, 1545/1994), and 62.81% (1260/2006) of the sample were female. In total, 3.88% (79/2036) of registrations appeared to be invalid and another 4.00% (81/2006) of participants gave inconsistent responses within the questionnaire. The higher value compensation (£20/US$32) increased response rates by 6-10%, boosting retention at 3 months to 77.2% (166/215) for submission of

  19. Sequential multiple assignment randomized trial (SMART) with adaptive randomization for quality improvement in depression treatment program.

    PubMed

    Cheung, Ying Kuen; Chakraborty, Bibhas; Davidson, Karina W

    2015-06-01

    Implementation study is an important tool for deploying state-of-the-art treatments from clinical efficacy studies into a treatment program, with the dual goals of learning about effectiveness of the treatments and improving the quality of care for patients enrolled into the program. In this article, we deal with the design of a treatment program of dynamic treatment regimens (DTRs) for patients with depression post-acute coronary syndrome. We introduce a novel adaptive randomization scheme for a sequential multiple assignment randomized trial of DTRs. Our approach adapts the randomization probabilities to favor treatment sequences having comparatively superior Q-functions used in Q-learning. The proposed approach addresses three main concerns of an implementation study: it allows incorporation of historical data or opinions, it includes randomization for learning purposes, and it aims to improve care via adaptation throughout the program. We demonstrate how to apply our method to design a depression treatment program using data from a previous study. By simulation, we illustrate that the inputs from historical data are important for the program performance measured by the expected outcomes of the enrollees, but also show that the adaptive randomization scheme is able to compensate poorly specified historical inputs by improving patient outcomes within a reasonable horizon. The simulation results also confirm that the proposed design allows efficient learning of the treatments by alleviating the curse of dimensionality.

  20. Naturopathic Care for Chronic Low Back Pain: A Randomized Trial

    PubMed Central

    Szczurko, Orest; Cooley, Kieran; Busse, Jason W.; Seely, Dugald; Bernhardt, Bob; Guyatt, Gordon H.; Zhou, Qi; Mills, Edward J.

    2007-01-01

    Objective Chronic low back pain represents a substantial cost to employers through benefits coverage and days missed due to incapacity. We sought to explore the effectiveness of Naturopathic care on chronic low back pain. Methods This study was a randomized clinical trial. We randomized 75 postal employees with low back pain of longer than six weeks duration to receive Naturopathic care (n = 39) or standardized physiotherapy (n = 36) over a period of 12 weeks. The study was conducted in clinics on-site in postal outlets. Participants in the Naturopathic care group received dietary counseling, deep breathing relaxation techniques and acupuncture. The control intervention received education and instruction on physiotherapy exercises using an approved education booklet. We measured low back pain using the Oswestry disability questionnaire as the primary outcome measure, and quality of life using the SF-36 in addition to low back range of motion, weight loss, and Body Mass Index as secondary outcomes. Results Sixty-nine participants (92%) completed eight weeks or greater of the trial. Participants in the Naturopathic care group reported significantly lower back pain (−6.89, 95% CI. −9.23 to −3.54, p = <0.0001) as measured by the Oswestry questionnaire. Quality of life was also significantly improved in the group receiving Naturopathic care in all domains except for vitality. Differences for the aggregate physical component of the SF-36 was 8.47 (95% CI, 5.05 to 11.87, p = <0.0001) and for the aggregate mental component was 7.0 (95% CI, 2.25 to 11.75, p = 0.0045). All secondary outcomes were also significantly improved in the group receiving Naturopathic care: spinal flexion (p<0.0001), weight-loss (p = 0.0052) and Body Mass Index (−0.52, 95% CI, −0.96 to −0.08, p = 0.01). Conclusions Naturopathic care provided significantly greater improvement than physiotherapy advice for patients with chronic low back pain. Trial Registration

  1. ORCHIDS: an Observational Randomized Controlled Trial on Childhood Differential Susceptibility

    PubMed Central

    2012-01-01

    Background A central tenet in developmental psychopathology is that childhood rearing experiences have a major impact on children’s development. Recently, candidate genes have been identified that may cause children to be differentially susceptible to these experiences (i.e., susceptibility genes). However, our understanding of the differential impact of parenting is limited at best. Specifically, more experimental research is needed. The ORCHIDS study will investigate gene-(gene-)environment interactions to obtain more insight into a) moderating effects of polymorphisms on the link between parenting and child behavior, and b) behavioral mechanisms that underlie these gene-(gene-)environment interactions in an experimental design. Methods/Design The ORCHIDS study is a randomized controlled trial, in which the environment will be manipulated with an intervention (i.e., Incredible Years parent training). In a screening, families with children aged 4–8 who show mild to (sub)clinical behavior problems will be targeted through community records via two Dutch regional healthcare organizations. Assessments in both the intervention and control condition will be conducted at baseline (i.e., pretest), after 6 months (i.e., posttest), and after 10 months (i.e., follow-up). Discussion This study protocol describes the design of a randomized controlled trial that investigates gene-(gene-)environment interactions in the development of child behavior. Two hypotheses will be tested. First, we expect that children in the intervention condition who carry one or more susceptibility genes will show significantly lower levels of problem behavior and higher levels of prosocial behavior after their parent(s) received the Incredible Years training, compared to children without these genes, or children in the control group. Second, we expect that children carrying one or more susceptibility genes will show a heightened sensitivity to changes in parenting behaviors, and will manifest

  2. A Randomized, Controlled Trial of ZMapp for Ebola Virus Infection

    PubMed Central

    2016-01-01

    BACKGROUND Data from studies in nonhuman primates suggest that the triple monoclonal antibody cocktail ZMapp is a promising immune-based treatment for Ebola virus disease (EVD). METHODS Beginning in March 2015, we conducted a randomized, controlled trial of ZMapp plus the current standard of care as compared with the current standard of care alone in patients with EVD that was diagnosed in West Africa by polymerase-chain-reaction (PCR) assay. Eligible patients of any age were randomly assigned in a 1:1 ratio to receive either the current standard of care or the current standard of care plus three intravenous infusions of ZMapp (50 mg per kilogram of body weight, administered every third day). Patients were stratified according to baseline PCR cycle-threshold value for the virus (≤22 vs. >22) and country of enrollment. Oral favipiravir was part of the current standard of care in Guinea. The primary end point was mortality at 28 days. RESULTS A total of 72 patients were enrolled at sites in Liberia, Sierra Leone, Guinea, and the United States. Of the 71 patients who could be evaluated, 21 died, representing an overall case fatality rate of 30%. Death occurred in 13 of 35 patients (37%) who received the current standard of care alone and in 8 of 36 patients (22%) who received the current standard of care plus ZMapp. The observed posterior probability that ZMapp plus the current standard of care was superior to the current standard of care alone was 91.2%, falling short of the prespecified threshold of 97.5%. Frequentist analyses yielded similar results (absolute difference in mortality with ZMapp, −15 percentage points; 95% confidence interval, −36 to 7). Baseline viral load was strongly predictive of both mortality and duration of hospitalization in all age groups. CONCLUSIONS In this randomized, controlled trial of a putative therapeutic agent for EVD, although the estimated effect of ZMapp appeared to be beneficial, the result did not meet the prespecified

  3. A Randomized, Controlled Trial of ZMapp for Ebola Virus Infection.

    PubMed

    Davey, Richard T; Dodd, Lori; Proschan, Michael A; Neaton, James; Neuhaus Nordwall, Jacquie; Koopmeiners, Joseph S; Beigel, John; Tierney, John; Lane, H Clifford; Fauci, Anthony S; Massaquoi, Moses B F; Sahr, Foday; Malvy, Denis

    2016-10-13

    Background Data from studies in nonhuman primates suggest that the triple monoclonal antibody cocktail ZMapp is a promising immune-based treatment for Ebola virus disease (EVD). Methods Beginning in March 2015, we conducted a randomized, controlled trial of ZMapp plus the current standard of care as compared with the current standard of care alone in patients with EVD that was diagnosed in West Africa by polymerase-chain-reaction (PCR) assay. Eligible patients of any age were randomly assigned in a 1:1 ratio to receive either the current standard of care or the current standard of care plus three intravenous infusions of ZMapp (50 mg per kilogram of body weight, administered every third day). Patients were stratified according to baseline PCR cycle-threshold value for the virus (≤22 vs. >22) and country of enrollment. Oral favipiravir was part of the current standard of care in Guinea. The primary end point was mortality at 28 days. Results A total of 72 patients were enrolled at sites in Liberia, Sierra Leone, Guinea, and the United States. Of the 71 patients who could be evaluated, 21 died, representing an overall case fatality rate of 30%. Death occurred in 13 of 35 patients (37%) who received the current standard of care alone and in 8 of 36 patients (22%) who received the current standard of care plus ZMapp. The observed posterior probability that ZMapp plus the current standard of care was superior to the current standard of care alone was 91.2%, falling short of the prespecified threshold of 97.5%. Frequentist analyses yielded similar results (absolute difference in mortality with ZMapp, -15 percentage points; 95% confidence interval, -36 to 7). Baseline viral load was strongly predictive of both mortality and duration of hospitalization in all age groups. Conclusions In this randomized, controlled trial of a putative therapeutic agent for EVD, although the estimated effect of ZMapp appeared to be beneficial, the result did not meet the prespecified

  4. Partner randomized controlled trial: study protocol and coaching intervention

    PubMed Central

    2012-01-01

    Background Many children with asthma live with frequent symptoms and activity limitations, and visits for urgent care are common. Many pediatricians do not regularly meet with families to monitor asthma control, identify concerns or problems with management, or provide self-management education. Effective interventions to improve asthma care such as small group training and care redesign have been difficult to disseminate into office practice. Methods and design This paper describes the protocol for a randomized controlled trial (RCT) to evaluate a 12-month telephone-coaching program designed to support primary care management of children with persistent asthma and subsequently to improve asthma control and disease-related quality of life and reduce urgent care events for asthma care. Randomization occurred at the practice level with eligible families within a practice having access to the coaching program or to usual care. The coaching intervention was based on the transtheoretical model of behavior change. Targeted behaviors included 1) effective use of controller medications, 2) effective use of rescue medications and 3) monitoring to ensure optimal control. Trained lay coaches provided parents with education and support for asthma care, tailoring the information provided and frequency of contact to the parent's readiness to change their child's day-to-day asthma management. Coaching calls varied in frequency from weekly to monthly. For each participating family, follow-up measurements were obtained at 12- and 24-months after enrollment in the study during a telephone interview. The primary outcomes were the mean change in 1) the child's asthma control score, 2) the parent's quality of life score, and 3) the number of urgent care events assessed at 12 and 24 months. Secondary outcomes reflected adherence to guideline recommendations by the primary care pediatricians and included the proportion of children prescribed controller medications, having maintenance

  5. A Randomized Controlled Trial of Mindfulness Meditation for Chronic Insomnia

    PubMed Central

    Ong, Jason C.; Manber, Rachel; Segal, Zindel; Xia, Yinglin; Shapiro, Shauna; Wyatt, James K.

    2014-01-01

    Study Objectives: To evaluate the efficacy of mindfulness meditation for the treatment of chronic insomnia. Design: Three-arm, single-site, randomized controlled trial. Setting: Academic medical center. Participants: Fifty-four adults with chronic insomnia. Interventions: Participants were randomized to either mindfulness-based stress reduction (MBSR), mindfulness-based therapy for insomnia (MBTI), or an eight-week self-monitoring (SM) condition. Measurements and Results: Patient-reported outcome measures were total wake time (TWT) from sleep diaries, the pre-sleep arousal scale (PSAS), measuring a prominent waking correlate of insomnia, and the Insomnia Severity Index (ISI) to determine remission and response as clinical endpoints. Objective sleep measures were derived from laboratory polysomnography and wrist actigraphy. Linear mixed models showed that those receiving a meditation-based intervention (MBSR or MBTI) had significantly greater reductions on TWT minutes (43.75 vs 1.09), PSAS (7.13 vs 0.16), and ISI (4.56 vs 0.06) from baseline-to-post compared to SM. Post hoc analyses revealed that each intervention was superior to SM on each of the patient-reported measures, but no significant differences were found when comparing MBSR to MBTI from baseline-to-post. From baseline to 6-month follow-up, MBTI had greater reductions in ISI scores than MBSR (P < 0.05), with the largest difference occurring at the 3-month follow-up. Remission and response rates in MBTI and MBSR were sustained from post-treatment through follow-up, with MBTI showing the highest rates of treatment remission (50%) and response (78.6%) at the 6-month follow-up. Conclusions: Mindfulness meditation appears to be a viable treatment option for adults with chronic insomnia and could provide an alternative to traditional treatments for insomnia. Trial Registration: Mindfulness-Based Approaches to Insomnia: clinicaltrials.gov, identifier: NCT00768781 Citation: Ong JC, Manber R, Segal Z, Xia Y

  6. Using Vascular Quality Initiative as a Platform for Organizing Multicenter, Prospective, Randomized Clinical Trials: OVERPAR Trial

    PubMed Central

    Eslami, Mohammad H.; Doros, Gheorghe; Goodney, Philip P.; Elderup-Jorgenson, Jens; Cronenwett, Jack L.; Malikova, Marina; Farber, Alik

    2014-01-01

    Background We describe the organization of a prospective, randomized, multicenter trial comparing the effectiveness of open popliteal artery aneurysm repair (OPAR) and endovascular popliteal artery aneurysm repair (EPAR) of asymptomatic popliteal artery aneurysms (PAAs) as an example for how to use the Vascular Quality Initiative (VQI) framework. Given that many centers participate in the VQI, this model can be used to perform multicenters’ prospective trials on very modest budget. Methods VQI prospectively collects data on many vascular procedures. These data include many important perioperative, intraoperative, and postoperative details regarding both patients and their procedures. We describe a study where minimal changes to the collected data by participating centers can provide level-1 evidence regarding a significant clinical question. Data will be collected using modified VQI forms within the existing VQI data reporting structure. We plan to enroll 148 patients with asymptomatic PAAs into the open and endovascular surgery cohorts. Patients from participating VQI centers will be randomized 1:1 to either OPAR or EPAR and will be followed for an average of 2.5 years. Our primary hypothesis is that major adverse limb event–free survival is lower in the EPAR cohort and that EPAR is associated with more secondary interventions, improved quality of life, and decreased length of stay. The budget for this trial is fixed at $10,000/year for the course of the study, and the trial is judged to be feasible because of the functionality of the VQI platform. Conclusions Using the existing VQI infrastructure, Open versus Endovascular Repair of Popliteal Artery Aneurysm will provide level 1 data for PAA treatment on a modest budget. The proposed trial has an adequately powered comparative design that will use objective performance goals to describe limb-related morbidity and procedural reintervention rates. PMID:25311746

  7. Cervical Spondylotic Myelopathy Surgical (CSM-S) Trial: Randomized Controlled Trial Design and Rationale

    PubMed Central

    Ghogawala, Zoher; Benzel, Edward C.; Heary, Robert F.; Riew, K. Daniel; Albert, Todd J.; Butler, William E.; Barker, Fred G.; Heller, John G.; McCormick, Paul C.; Whitmore, Robert G.; Freund, Karen M.; Schwartz, J. Sanford

    2014-01-01

    Background Cervical spondylotic myelopathy (CSM) is the most common cause of spinal cord dysfunction in the world. There is significant practice variation and uncertainty as to the optimal surgical approach for treating CSM. Objective The primary objective is to determine if ventral surgery is associated with superior SF-36 Physical Component Summary (PCS) outcome at one year follow-up compared to dorsal (laminectomy/fusion or laminoplasty) surgery for the treatment of CSM. The study will also investigate whether post-operative sagittal balance is an independent predictor of overall outcome and will compare health resource utilization for ventral and dorsal procedures. Methods The study is a randomized, controlled trial with a nonrandomized arm for patients who are eligible but decline randomization. Two hundred fifty patients (159 randomized) with CSM from 11 sites will be recruited over 18 months. The primary outcome is the Short Form-36 PCS score. Secondary outcomes include disease specific outcomes, overall health-related quality of life (EuroQol-5D), and health resource utilization. Expected Outcomes This will be the first randomized controlled trial to compare directly the health-related quality of life outcomes for ventral versus dorsal surgery for treating CSM. Discussion An NIH-funded (1R13AR065834-01) investigator meeting was held prior to initiating the trial in order to bring multiple stakeholders together to finalize the study protocol. Study investigators, coordinators, and major stakeholders were able to attend and discuss strengths, limitations, and concerns regarding the study. The final protocol was approved for funding by PCORI (CE-1304-6173). The RCT began enrollment on April 1, 2014. PMID:24991714

  8. The Chronic Kidney Disease Water Intake Trial: Protocol of a Randomized Controlled Trial.

    PubMed

    Clark, William F; Huang, Shih-Han; Garg, Amit X; Gallo, Kerri; House, Andrew A; Moist, Louise; Weir, Matthew A; Sontrop, Jessica M

    2017-01-01

    In observational studies, drinking more water associates with a slower rate of kidney function decline; whether the same is true in a randomized controlled trial is unknown. To examine the 1-year effect of a higher vs usual water intake on estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease. Parallel-group randomized controlled trial. Nine centers in Ontario, Canada. Enrollment and randomization occurred between May 2013 and May 2016; follow-up for the primary outcome will continue until June 2017. Adults (n = 631) with stage 3 chronic kidney disease (eGFR 30-60 mL/min/1.73 m(2)) and microalbuminuria. The high water intake group was coached to increase their oral water intake by 1.0 to 1.5 L/day (depending on sex and weight), over and above usual consumed beverages, for a period of 1 year. The control group was coached to maintain their usual water intake during this time. Participants provided 24-hour urine samples at baseline and at 6 and 12 months after randomization; urine samples were analyzed for volume, creatinine, osmolality, and the albumin-to-creatinine ratio. Blood samples were obtained at baseline and at 3- to 6-month intervals after randomization, and analyzed for creatinine, copeptin, osmolality, and electrolytes. Other measures collected included health-related quality of life, blood pressure, body mass index, and diet. The between-group change in eGFR from baseline (prerandomization) to 12 months after randomization. Change in plasma copeptin concentration, 24-hour urine albumin-to-creatinine ratio, measured creatinine clearance, estimated 5-year risk of kidney failure (using the 4-variable Kidney Failure Risk Equation), and health-related quality of life. The primary analysis will follow an intention-to-treat approach. The between-group change in eGFR will be compared using linear regression. Supplementary analyses will examine alternative definitions of eGFR change, including annual percentage change, rate of

  9. Guidelines for randomized clinical trial protocol content: a systematic review

    PubMed Central

    2012-01-01

    Background All randomized clinical trials (RCTs) require a protocol; however, numerous studies have highlighted protocol deficiencies. Reporting guidelines may improve the content of research reports and, if developed using robust methods, may increase the utility of reports to stakeholders. The objective of this study was to systematically identify and review RCT protocol guidelines, to assess their characteristics and methods of development, and to compare recommendations. Methods We conducted a systematic review of indexed literature (MEDLINE, EMBASE and the Cochrane Methodology Register from inception to September 2010; reference lists; related article features; forward citation searching) and a targeted search of supplementary sources, including a survey of major trial funding agencies in six countries. Records were eligible if they described a content guideline in English or French relevant to RCT protocols. Guidelines were excluded if they specified content for protocols for trials of specific procedures or conditions or were intended to assess trial quality. We extracted guideline characteristics and methods. Content was mapped for a subset of guidelines that described development methods or had institutional endorsement. Results Forty guidelines published in journals, books and institutional reports were included in the review; seven were specific to RCT protocols. Only eight (20%) described development methods which included informal consensus methods, pilot testing and formal validation; no guideline described all of these methods. No guideline described formal consensus methods or a systematic retrieval of empirical evidence to inform its development. The guidelines included a median of 23 concepts per guideline (interquartile range (IQR) = 14 to 34; range = 7 to 109). Among the subset of guidelines (n = 23) for which content was mapped, approximately 380 concepts were explicitly addressed (median concepts per guideline IQR = 31 (24

  10. [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.

  11. Randomized trial of a patient-centered hospital unit.

    PubMed

    Martin, D P; Diehr, P; Conrad, D A; Davis, J H; Leickly, R; Perrin, E B

    1998-06-01

    Patient-centered hospital units have grown out of the national trend to greater consumerism, but few of these units have been evaluated rigorously. We used a randomized controlled trial to compare patient outcomes on the Planetree Model Hospital Unit with other medical-surgical units in the hospital. Planetree patients were significantly more satisfied than controls with their hospital stay, the unit's environment and nursing care, but did not differ in ratings of physician care. Planetree patients reported more involvement in their care while hospitalized and higher satisfaction with the education they received. There were few differences between Planetree and controls in health behaviors. While Planetree patients reported better mental health status and role functioning after discharge, their health status was similar to controls after 3 to 6 months. There were no differences in length of stay and charges for the index hospitalization, readmissions or outpatient care during the following year.

  12. Randomized Trial of a Brief Depression Prevention Program

    PubMed Central

    Stice, Eric; Burton, Emily; Bearman, Sarah Kate; Rohde, Paul

    2008-01-01

    This trial compared a brief group cognitive-behavioral (CBT) depression prevention program to a waitlist control condition and four placebo or alternative interventions. High-risk adolescents with elevated depressive symptoms (N = 225, M age = 18, 70% female) were randomized to CBT, supportive-expressive group intervention, bibliotherapy, expressive writing, journaling, or waitlist conditions and completed assessments at baseline, termination, and 1-month and 6-month follow-up. All five active interventions showed significantly greater reductions in depressive symptoms at termination than waitlist controls; effects for CBT and bibliotherapy persisted into follow-up. CBT, supportive-expressive, and bibliotherapy participants also showed significantly greater decreases in depressive symptoms than expressive writing and journaling participants at certain follow-up points. Findings suggest there may be multiple ways to reduce depressive symptoms in high-risk adolescents, although expectancies, demand characteristics, and attention may have contributed to the observed effects. PMID:17007812

  13. A randomized trial of minoxidil in chemotherapy-induced alopecia.

    PubMed

    Duvic, M; Lemak, N A; Valero, V; Hymes, S R; Farmer, K L; Hortobagyi, G N; Trancik, R J; Bandstra, B A; Compton, L D

    1996-07-01

    Hair loss is a side effect of many chemotherapeutic agents, and patients have even refused possibly palliative or lifesaving drugs because they could not accept temporary or prolonged baldness. Topical minoxidil has been shown to be effective for androgenetic alopecia and alopecia areata. Our purpose was to investigate the value and safety of minoxidil in chemotherapy-induced hair loss. Twenty-two women who were facing adjuvant chemotherapy after breast surgery were registered in a protocol that used a 2% minoxidil topical solution or a placebo in a randomized double-blind trial. There was a statistically significant difference (favoring minoxidil) in the interval from maximal hair loss to first regrowth. Thus the period of baldness was shortened (mean, 50.2 days) in the minoxidil group. Minoxidil decreased the duration of alopecia caused by chemotherapy. There were no significant side effects.

  14. Randomized controlled trial quality in pediatric physical therapy.

    PubMed

    Paci, Matteo; Landi, Niccolò; Marchettini, Mariangela; Baccini, Marco

    2014-08-01

    The aim of this study is to describe the reported quality of randomized controlled trials (RCTs) in pediatric physical therapy (PPT) and changes with time. All RCTs sourced from PEDro database and scored using the PEDro scale were included. RCTs were classified as high- or low quality both with the original cut-off of 6 and a modified cut-off of 5. The relationship between PEDro scores and year of publication was also investigated. One thousand three hundred sixty-seven articles were analyzed. According to the PEDro scale original and modified cut-off, 29% and 56% of the articles were classified as high-quality studies, respectively. The number of RCTs and the average PEDro score increased between 1962 and 2012. However, since some items of the scale could be more frequently satisfied, a further improvement of the quality of RCTs in PPT is recommended.

  15. Testimony Therapy With Ritual: A Pilot Randomized Controlled Trial.

    PubMed

    Esala, Jennifer J; Taing, Sopheap

    2017-02-01

    Testimony therapy can provide low-cost, brief, simple, and culturally adaptable psychosocial services in low-income countries (Agger, Raghuvanshi, Khan, Polatin, & Laursen, 2009). Nonetheless, there have been no well-controlled studies of testimony therapy. We report the analyses of a randomized controlled trial designed to assess the effectiveness of testimony therapy plus a culturally adapted ceremony in reducing mental health symptoms among Khmer Rouge torture survivors from across Cambodia. Using multilevel modeling, we compared symptoms of posttraumatic stress disorder, anxiety, and depression between a treatment (n = 45) and a control group (n = 43) at baseline, 3 months, and 6 months. We found that testimony therapy plus ceremony significantly reduced symptoms of posttraumatic stress disorder (d = 0.49), anxiety (d = 0.44), and depression (d = 0.53).

  16. Philosophers assess randomized clinical trials: the need for dialogue.

    PubMed

    Miké, V

    1989-09-01

    In recent years a growing number of professional philosophers have joined in the controversy over ethical aspects of randomized clinical trials (RCTs). Morally questionable in their utilitarian approach, RCTs are claimed by some to be in direct violation of the second form of Kant's Categorical Imperative. But the arguments used in these critiques at times derive from a lack of insight into basic statistical procedures and the realities of the biomedical research process. Presented to physicians and other nonspecialists, including the lay public, such distortions can be harmful. Given the great complexity of statistical methodology and the anomalous nature of concepts of evidence, more sustained input into the interdisciplinary dialogue is needed from the statistical profession.

  17. Handling clinical comorbidity in randomized clinical trials in psychiatry.

    PubMed

    O'Hara, Ruth; Beaudreau, Sherry A; Gould, Christine E; Froehlich, Wendy; Kraemer, Helena C

    2017-03-01

    The purpose of this paper is to a) outline the importance of including patients with clinical comorbidities in Randomized Clinical Trials (RCTs) of psychiatric treatments; and b) to propose a specific approach for best handling, analyzing and interpreting the data on clinical comorbidities in terms of their impact on treatment outcomes. To do this we first define and describe clinical comorbidity and differentiate it from other forms of comorbidity. We then describe the methodological and analytical problems associated with excluding patients with clinically comorbid conditions from RCTs, including the impact on the outcomes of RCTs in psychiatry and the impact on evidence-based clinical decision-making. We then address the challenges inherent to including patients with clinical comorbidities in RCTs. Finally, we propose a methodological and analytic approach to deal with these issues in RCTs which aims to significantly improve the information yielded from RCTs in psychiatry, and thus improve clinical decision-making.

  18. Randomized controlled trials in environmental health research: ethical issues.

    PubMed

    Resnik, David B

    2008-01-01

    Randomized controlled trials (RCTs) are becoming increasingly common in environmental health research. Like all studies involving human subjects, environmental health RCTs raise many ethical challenges, ranging from obtaining informed consent to minimizing risks to protecting privacy and confidentiality. One of the most important issues raised by these studies is whether it is ethical to withhold effective environmental health interventions from research subjects in order to satisfy scientific objectives. Although environmental health investigators usually do not have professional obligations to provide medical care to research subjects, they have ethical obligations to avoid exploiting them. Withholding interventions from research subjects can be ethical, provided that it does not lead to exploitation of individuals or groups. To avoid exploiting individuals or groups, investigators should ensure that research subjects and study populations receive a fair share of the benefits of research.

  19. Randomized Trial of Enhanced Profiling in Substance Abuse Treatment

    PubMed Central

    Daley, Marilyn; Tompkins, Christopher; Dunigan, Robert; Reif, Sharon; Perloff, Jennifer; Siembab, Lauren; Horgan, Constance

    2010-01-01

    A randomized trial of substance abuse treatment programs tested whether “enhanced profiles,” consisting of feedback and coaching about performance indicators, improved the performance of residential, methadone, and detoxification programs. These enhanced profiles were reviewed during quarterly on-site visits between October 2005 and July 2007. The performance indicators were the percentage of clients completing referrals to a lower level of care, and the percentage of clients admitted to a higher level of care within 30 days of discharge. Control programs received only “basic profiles,” consisting of emailed quarterly printouts of these performance indicators. Effectiveness was evaluated using hierarchical linear models with client-level information nested within agencies and regions of the state. Treatment programs receiving enhanced profiles (n = 74) did not perform significantly differently from those receiving only basic profiles (n = 29) on either performance measure. To improve performance, interventions with greater scope and incentives may be needed. PMID:20680676

  20. A randomized controlled trial to promote volunteering in older adults.

    PubMed

    Warner, Lisa M; Wolff, Julia K; Ziegelmann, Jochen P; Wurm, Susanne

    2014-12-01

    Volunteering is presumed to confer health benefits, but interventions to encourage older adults to volunteer are sparse. Therefore, a randomized controlled trial with 280 community-dwelling older German adults was conducted to test the effects of a theory-based social-cognitive intervention against a passive waiting-list control group and an active control intervention designed to motivate physical activity. Self-reports of weekly volunteering minutes were assessed at baseline (5 weeks before the intervention) as well as 2 and 6 weeks after the intervention. Participants in the treatment group increased their weekly volunteering minutes to a greater extent than participants in the control groups 6 weeks after the intervention. We conclude that a single, face-to-face group session can increase volunteering among older community-dwelling adults. However, the effects need some time to unfold because changes in volunteering were not apparent 2 weeks after the intervention.

  1. [Insulin infusion in intensive care: randomized controlled trial].

    PubMed

    Miranda, Milena Penteado Ferraro; Crespo, Jeiel Carlos Lamonica; Secoli, Silvia Regina

    2013-06-01

    This randomized controlled trial compared the use of an intensive and conventional insulin protocol on clinical outcomes in patients with severe sepsis and septic shock, in the first 72 hours. It was conducted at a university hospital in the city of São Paulo. Patients (n=46) were allocated into two groups: intensive glycemic (blood glucose between 80-110mg/dl) and conventional (180-220mg/dl). The Student's t-test and chi-square test were used for data analysis. A statistically significant (p<0.001) difference was observed in mean glycemia, but there was no difference in the variables of mean minimum arterial pressure (p=0.06) or maximum (p=0.11), serum creatinine (p=0,33) or in mortality (p=0.11). Although there was no difference between the groups regarding mortality, hemodynamic instability in the conventional group was longer and the only deaths occurred in it.

  2. A randomized trial on root caries prevention in elders.

    PubMed

    Tan, H P; Lo, E C M; Dyson, J E; Luo, Y; Corbet, E F

    2010-10-01

    Root caries is common in institutionalized elders, and effective prevention methods are needed. This clinical trial compared the effectiveness of four methods in preventing new root caries. From 21 residential homes, 306 generally healthy elders having at least 5 teeth with exposed sound root surfaces were randomly allocated into one of four groups: (1) individualized oral hygiene instruction (OHI); (2) OHI and applications of 1% chlorhexidine varnish every 3 months; (3) OHI and applications of 5% sodium fluoride varnish every 3 months; and (4) OHI and annual applications of 38% silver diamine fluoride (SDF) solution. Two-thirds (203/306) of the elders were followed for 3 years. Mean numbers of new root caries surfaces in the four groups were 2.5, 1.1, 0.9, and 0.7, respectively (ANOVA, p < 0.001). SDF solution, sodium fluoride varnish, and chlorhexidine varnish were more effective in preventing new root caries than giving OHI alone.

  3. Positive Psychotherapy for Smoking Cessation: A Pilot Randomized Controlled Trial

    PubMed Central

    Spillane, Nichea S.; Day, Anne M.; Cioe, Patricia A.; Parks, Acacia; Leventhal, Adam M.; Brown, Richard A.

    2015-01-01

    Objective: Greater depressive symptoms and low positive affect (PA) are associated with poor smoking cessation outcomes. Smoking cessation approaches that incorporate a focus on PA may benefit smokers trying to quit. The purpose of this study was to conduct a pilot randomized clinical trial to compare standard smoking cessation treatment (ST) with smoking cessation treatment that targets positive affect, termed positive psychotherapy for smoking cessation (PPT-S). Method: Smokers who were seeking smoking cessation treatment were assigned by urn randomization to receive, along with 8 weeks of nicotine replacement therapy, either ST (n = 31) or PPT-S (n = 35). Seven-day point prevalence smoking abstinence was biochemically confirmed at 8, 16, and 26 weeks. Results: Compared to ST, a greater percentage of participants in PPT-S were abstinent at 8 weeks, 16 weeks, and 26 weeks, but these differences were nonsignificant. In a more statistically powerful longitudinal model, participants in PPT-S had a significantly higher odds of abstinence (adjusted odds ratio [AOR] = 2.75; 95% CI = 1.02, 7.42; p = .046) across follow-ups compared to those in ST. The positive effect of PPT-S was stronger for those higher in PA (OR = 6.69, 95% CI = 1.16, 38.47, p = .03). Greater use of PPT-S strategies during the initial 8 weeks of quitting was associated with a less steep decline in smoking abstinence rates over time (OR = 2.64, 95% CI = 1.06, 6.56, p =.04). Conclusion: This trial suggests substantial promise for incorporating PPT into smoking cessation treatment. PMID:25646352

  4. Computerized Tool to Manage Dental Anxiety: A Randomized Clinical Trial.

    PubMed

    Tellez, M; Potter, C M; Kinner, D G; Jensen, D; Waldron, E; Heimberg, R G; Myers Virtue, S; Zhao, H; Ismail, A I

    2015-09-01

    Anxiety regarding dental and physical health is a common and potentially distressing problem, for both patients and health care providers. Anxiety has been identified as a barrier to regular dental visits and as an important target for enhancement of oral health-related quality of life. The study aimed to develop and evaluate a computerized cognitive-behavioral therapy dental anxiety intervention that could be easily implemented in dental health care settings. A cognitive-behavioral protocol based on psychoeducation, exposure to feared dental procedures, and cognitive restructuring was developed. A randomized controlled trial was conducted (N = 151) to test its efficacy. Consenting adult dental patients who met inclusion criteria (e.g., high dental anxiety) were randomized to 1 of 2 groups: immediate treatment (n = 74) or a wait-list control (n = 77). Analyses of covariance based on intention-to-treat analyses were used to compare the 2 groups on dental anxiety, fear, avoidance, and overall severity of dental phobia. Baseline scores on these outcomes were entered into the analyses as covariates. Groups were equivalent at baseline but differed at 1-mo follow-up. Both groups showed improvement in outcomes, but analyses of covariance demonstrated significant differences in dental anxiety, fear, avoidance, and overall severity of dental phobia in favor of immediate treatment at the follow-up assessment. Of the patients who met diagnostic criteria for phobia at baseline, fewer patients in the immediate treatment group continued to meet criteria for dental phobia at follow-up as compared with the wait-list group. A new computer-based tool seems to be efficacious in reducing dental anxiety and fear/avoidance of dental procedures. Examination of its effectiveness when administered in dental offices under less controlled conditions is warranted (ClinicalTrials.gov NCT02081365).

  5. Dressing Wear Time after Breast Reconstruction: A Randomized Clinical Trial.

    PubMed

    Veiga, Daniela Francescato; Damasceno, Carlos Américo Veiga; Veiga-Filho, Joel; Paiva, Luiz Francisley; Fonseca, Fernando Elias Martins; Cabral, Isaías Vieira; Pinto, Natália Lana Larcher; Juliano, Yara; Ferreira, Lydia Masako

    2016-01-01

    The evidence to support dressing standards for breast surgery wounds is empiric and scarce. This two-arm randomized clinical trial was designed to assess the effect of dressing wear time on surgical site infection (SSI) rates, skin colonization and patient perceptions. A total of 200 breast cancer patients undergoing breast reconstruction were prospectively enrolled. Patients were randomly allocated to group I (dressing removed on the first postoperative day, n = 100) or group II (dressing removed on the sixth postoperative day, n = 100). SSIs were defined and classified according to criteria from the Centers for Disease Control and Prevention. Samples collected before placing the dressing and after 1 day (group I) and 6 days (both groups) were cultured for skin colonization assessments. Patients preferences and perceptions with regard to safety, comfort and convenience were recorded and analyzed. A total of 186 patients completed the follow-up. The global SSI rate was 4.5%. Six patients in group I and three in group II had SSI (p = 0.497). Before dressing, the groups were similar with regard to skin colonization. At the sixth day, there was a higher colonization by coagulase-negative staphylococci in group I (p<0.0001). Patients preferred to keep dressing for six days (p<0.0001), and considered this a safer choice (p<0.05). Despite group I had a higher skin colonization by coagulase-negative staphylococci on the sixth postoperative day, there was no difference in SSI rates. Patients preferred keeping dressing for six days and considered it a safer choice. ClinicalTrials.gov NCT01148823.

  6. Randomized Controlled Trial of Primary Care Pediatric Parenting Programs

    PubMed Central

    Mendelsohn, Alan L.; Dreyer, Benard P.; Brockmeyer, Carolyn A.; Berkule-Silberman, Samantha B.; Huberman, Harris S.; Tomopoulos, Suzy

    2011-01-01

    Objectives To determine whether pediatric primary care–based programs to enhance parenting and early child development reduce media exposure and whether enhanced parenting mediates the effects. Design Randomized controlled trial. Setting Urban public hospital pediatric primary care clinic. Participants A total of 410 mother-newborn dyads enrolled after childbirth. Interventions Patients were randomly assigned to 1 of 2 interventions, the Video Interaction Project (VIP) and Building Blocks (BB) interventions, or to a control group. The VIP intervention comprised 1-on-1 sessions with a child development specialist who facilitated interactions in play and shared reading through review of videotapes made of the parent and child on primary care visit days; learning materials and parenting pamphlets were also provided. The BB intervention mailed parenting materials, including age-specific newsletters suggesting activities to facilitate interactions, learning materials, and parent-completed developmental questionnaires (Ages and Stages questionnaires). Outcome Measures Electronic media exposure in the home using a 24-hour recall diary. Results The mean (SD) exposure at 6 months was 146.5 (125.0) min/d. Exposure to VIP was associated with reduced total duration of media exposure compared with the BB and control groups (mean [SD] min/d for VIP, 131.6 [118.7]; BB, 151.2 [116.7]; control, 155.4 [138.7]; P=.009). Enhanced parent-child interactions were found to partially mediate relations between VIP and media exposure for families with a ninth grade or higher literacy level (Sobel statistic=2.49; P=.01). Conclusion Pediatric primary care may represent an important venue for addressing the public health problem of media exposure in young children at a population level. Trial Registration clinicaltrials.gov Identifier: NCT00212576 PMID:21199979

  7. Acupuncture for Menopausal Hot Flashes: A Randomized Trial.

    PubMed

    Ee, Carolyn; Xue, Charlie; Chondros, Patty; Myers, Stephen P; French, Simon D; Teede, Helena; Pirotta, Marie

    2016-02-02

    Hot flashes (HFs) affect up to 75% of menopausal women and pose a considerable health and financial burden. Evidence of acupuncture efficacy as an HF treatment is conflicting. To assess the efficacy of Chinese medicine acupuncture against sham acupuncture for menopausal HFs. Stratified, blind (participants, outcome assessors, and investigators, but not treating acupuncturists), parallel, randomized, sham-controlled trial with equal allocation. (Australia New Zealand Clinical Trials Registry: ACTRN12611000393954). Community in Australia. Women older than 40 years in the late menopausal transition or postmenopause with at least 7 moderate HFs daily, meeting criteria for Chinese medicine diagnosis of kidney yin deficiency. 10 treatments over 8 weeks of either standardized Chinese medicine needle acupuncture designed to treat kidney yin deficiency or noninsertive sham acupuncture. The primary outcome was HF score at the end of treatment. Secondary outcomes included quality of life, anxiety, depression, and adverse events. Participants were assessed at 4 weeks, the end of treatment, and then 3 and 6 months after the end of treatment. Intention-to-treat analysis was conducted with linear mixed-effects models. 327 women were randomly assigned to acupuncture (n = 163) or sham acupuncture (n = 164). At the end of treatment, 16% of participants in the acupuncture group and 13% in the sham group were lost to follow-up. Mean HF scores at the end of treatment were 15.36 in the acupuncture group and 15.04 in the sham group (mean difference, 0.33 [95% CI, -1.87 to 2.52]; P = 0.77). No serious adverse events were reported. Participants were predominantly Caucasian and did not have breast cancer or surgical menopause. Chinese medicine acupuncture was not superior to noninsertive sham acupuncture for women with moderately severe menopausal HFs. National Health and Medical Research Council.

  8. Exercise in Patients on Dialysis: A Multicenter, Randomized Clinical Trial.

    PubMed

    Manfredini, Fabio; Mallamaci, Francesca; D'Arrigo, Graziella; Baggetta, Rossella; Bolignano, Davide; Torino, Claudia; Lamberti, Nicola; Bertoli, Silvio; Ciurlino, Daniele; Rocca-Rey, Lisa; Barillà, Antonio; Battaglia, Yuri; Rapanà, Renato Mario; Zuccalà, Alessandro; Bonanno, Graziella; Fatuzzo, Pasquale; Rapisarda, Francesco; Rastelli, Stefania; Fabrizi, Fabrizio; Messa, Piergiorgio; De Paola, Luciano; Lombardi, Luigi; Cupisti, Adamasco; Fuiano, Giorgio; Lucisano, Gaetano; Summaria, Chiara; Felisatti, Michele; Pozzato, Enrico; Malagoni, Anna Maria; Castellino, Pietro; Aucella, Filippo; Abd ElHafeez, Samar; Provenzano, Pasquale Fabio; Tripepi, Giovanni; Catizone, Luigi; Zoccali, Carmine

    2017-04-01

    Previous studies have suggested the benefits of physical exercise for patients on dialysis. We conducted the Exercise Introduction to Enhance Performance in Dialysis trial, a 6-month randomized, multicenter trial to test whether a simple, personalized walking exercise program at home, managed by dialysis staff, improves functional status in adult patients on dialysis. The main study outcomes included change in physical performance at 6 months, assessed by the 6-minute walking test and the five times sit-to-stand test, and in quality of life, assessed by the Kidney Disease Quality of Life Short Form (KDQOL-SF) questionnaire. We randomized 296 patients to normal physical activity (control; n=145) or walking exercise (n=151); 227 patients (exercise n=104; control n=123) repeated the 6-month evaluations. The distance covered during the 6-minute walking test improved in the exercise group (mean distance±SD: baseline, 328±96 m; 6 months, 367±113 m) but not in the control group (baseline, 321±107 m; 6 months, 324±116 m; P<0.001 between groups). Similarly, the five times sit-to-stand test time improved in the exercise group (mean time±SD: baseline, 20.5±6.0 seconds; 6 months, 18.2±5.7 seconds) but not in the control group (baseline, 20.9±5.8 seconds; 6 months, 20.2±6.4 seconds; P=0.001 between groups). The cognitive function score (P=0.04) and quality of social interaction score (P=0.01) in the kidney disease component of the KDQOL-SF improved significantly in the exercise arm compared with the control arm. Hence, a simple, personalized, home-based, low-intensity exercise program managed by dialysis staff may improve physical performance and quality of life in patients on dialysis. Copyright © 2017 by the American Society of Nephrology.

  9. Randomized controlled trial of Anticipatory and Preventive multidisciplinary Team Care

    PubMed Central

    Hogg, William; Lemelin, Jacques; Dahrouge, Simone; Liddy, Clare; Armstrong, Catherine Deri; Legault, Frances; Dalziel, Bill; Zhang, Wei

    2009-01-01

    ABSTRACT OBJECTIVE T o examine whether quality of care (QOC) improves when nurse practitioners and pharmacists work with family physicians in community practice and focus their work on patients who are 50 years of age and older and considered to be at risk of experiencing adverse health outcomes. DESIGN Randomized controlled trial. SETTING A family health network with 8 family physicians, 5 nurses, and 11 administrative personnel serving 10 000 patients in a rural area near Ottawa, Ont. PARTICIPANTS Patients 50 years of age and older at risk of experiencing adverse health outcomes (N = 241). INTERVENTIONS At-risk patients were randomly assigned to receive usual care from their family physicians or Anticipatory and Preventive Team Care (APTCare) from a collaborative team composed of their physicians, 1 of 3 nurse practitioners, and a pharmacist. MAIN OUTCOME MEASURES Quality of care for chronic disease management (CDM) for diabetes, coronary artery disease, congestive heart failure, and chronic obstructive pulmonary disease. RESULTS Controlling for baseline demographic characteristics, the APTCare approach improved CDM QOC by 9.2% (P < .001) compared with traditional care. The APTCare intervention also improved preventive care by 16.5% (P < .001). We did not observe significant differences in other secondary outcome measures (intermediate clinical outcomes, quality of life [Short-Form 36 and health-related quality of life scales], functional status [instrumental activities of daily living scale] and service usage). CONCLUSION Additional resources in the form of collaborative multidisciplinary care teams with intensive interventions in primary care can improve QOC for CDM in a population of older at-risk patients. The appropriateness of this intervention will depend on its cost-effectiveness. TRIAL REGISTRATION NUMBER NCT00238836 (CONSORT) PMID:20008582

  10. A randomized controlled trial of qigong for fibromyalgia

    PubMed Central

    2012-01-01

    Introduction Fibromyalgia is difficult to treat and requires the use of multiple approaches. This study is a randomized controlled trial of qigong compared with a wait-list control group in fibromyalgia. Methods One hundred participants were randomly assigned to immediate or delayed practice groups, with the delayed group receiving training at the end of the control period. Qigong training (level 1 Chaoyi Fanhuan Qigong, CFQ), given over three half-days, was followed by weekly review/practice sessions for eight weeks; participants were also asked to practice at home for 45 to 60 minutes per day for this interval. Outcomes were pain, impact, sleep, physical function and mental function, and these were recorded at baseline, eight weeks, four months and six months. Immediate and delayed practice groups were analyzed individually compared to the control group, and as a combination group. Results In both the immediate and delayed treatment groups, CFQ demonstrated significant improvements in pain, impact, sleep, physical function and mental function when compared to the wait-list/usual care control group at eight weeks, with benefits extending beyond this time. Analysis of combined data indicated significant changes for all measures at all times for six months, with only one exception. Post-hoc analysis based on self-reported practice times indicated greater benefit with the per protocol group compared to minimal practice. Conclusions This study demonstrates that CFQ, a particular form of qigong, provides long-term benefits in several core domains in fibromyalgia. CFQ may be a useful adjuvant self-care treatment for fibromyalgia. Trial registration clinicaltrials.gov NCT00938834. PMID:22863206

  11. Random allocation or allocation at random? Patients’ perspectives of participation in a randomised controlled trial

    PubMed Central

    Featherstone, Katie; Donovan, Jenny L

    1998-01-01

    describe various aspects of randomisation, including the involvement of chance, comparison, and concealed allocationThe majority found the concept of randomisation difficult to accept and developed other accounts to make sense of their experiencesThe use of terms which have different meanings to lay and professional audiences (such as trial and random) can cause confusion among participantsProviding clear and accurate patient information is crucial, but to give truly informed consent patients may also need time to discuss the purposes of clinical trials and concepts such as randomisation PMID:9794849

  12. A randomized crossover clinical trial of sertraline for intradialytic hypotension.

    PubMed

    Razeghi, Effat; Dashti-Khavidaki, Simin; Nassiri, Samira; Abolghassemi, Rozita; Khalili, Hossein; Hashemi Nazari, Seyed Saeed; Mansournia, Mohammad Ali; Taraz, Mohammad

    2015-07-01

    Intradialytic hypotension (IDH) has been reported in 15% to 50% of hemodialysis patients and increases patients morbidity and mortality. Some small noncontrolled studies evaluated the effect of sertraline on IDH with conflicting results. This study is a randomized crossover controlled trial on the effectiveness of sertraline to reduce IDH. Patients on hemodialysis who suffered IDH in at least 50% of their dialysis sessions were enrolled. Each patient received either sertraline or placebo for 4 weeks and after a 4-week washout period, was switched to the other arm of the trial. All patients started sertraline at a daily dose of 50 mg that increased to 100 mg after 1 week. Twelve patients completed all phases of the study. Sertraline therapy increased nadir intradialysis diastolic and systolic blood pressure by 3.8 mm Hg and 4.9 mm Hg at the end of the intervention, respectively. Sertraline therapy also significantly increased postdialysis diastolic and systolic blood pressure by 6.0 mm Hg and 8.7 mm Hg. Sertraline therapy significantly reduced the risk of hypotension episodes by 43%. The improvement of intradialysis and postdialysis diastolic and systolic blood pressure were only significant in nondiabetic patients. Sertraline therapy significantly increases intradialysis and postdialysis blood pressure. These effects of sertraline can result in significant decrease in hypotension episodes during dialysis treatment and the number of interventions required to manage IDH. However, not all patients may benefit from sertraline depending on comorbidities such as diabetes mellitus.

  13. Anethum graveolens and hyperlipidemia: A randomized clinical trial

    PubMed Central

    Mirhosseini, Mahmoud; Baradaran, Azar; Rafieian-Kopaei, Mahmoud

    2014-01-01

    Background: It has been established that hyperlipidemia increases the incidence and mortality associated with coronary heart disease. In this study, the effects of Dill (Anethum graveolens) were evaluated on lipid profile of hypercholesterolemic patients. Materials and Methods: In this clinical study, 91 hyperlipidemic patients were randomly designated into two groups. One group received gemfibrozil (900 mg daily) and the other group received Dill tablet (six tablets daily) for 2 months. The blood lipids including total cholesterol, triglyceride and high density lipoprotein (HDL)-cholesterol from each group were assessed at the beginning and end of the trial. Results: Use of gemfibrozil brought about increased HDL-cholesterol by 3.91% (P < 0.05) and reduced triglyceride and total cholesterol by 32.7% (P < 0.05) and 9.41% (P < 0.05), respectively. Applying Dill tablet for 2 months resulted in reduction of total cholesterol up to 18% (P < 0.05) and triglyceride by 7.38% (P < 0.05). However, circulating HDL-cholesterol was not affected by this treatment. In this study, gemfibrozil decreased triglyceride and increased HDL-cholesterol more than anethum (P < 0.05). Anethum decreased total cholesterol more than gemfibrozil (P < 0.05). Patients treated with anethum did not report any side effects. Conclusion: The results of this trial indicate that Dill might be beneficial for hypercholesterolemic and hypertriglycemic patients. PMID:25422662

  14. Anethum graveolens and hyperlipidemia: A randomized clinical trial.

    PubMed

    Mirhosseini, Mahmoud; Baradaran, Azar; Rafieian-Kopaei, Mahmoud

    2014-08-01

    It has been established that hyperlipidemia increases the incidence and mortality associated with coronary heart disease. In this study, the effects of Dill (Anethum graveolens) were evaluated on lipid profile of hypercholesterolemic patients. In this clinical study, 91 hyperlipidemic patients were randomly designated into two groups. One group received gemfibrozil (900 mg daily) and the other group received Dill tablet (six tablets daily) for 2 months. The blood lipids including total cholesterol, triglyceride and high density lipoprotein (HDL)-cholesterol from each group were assessed at the beginning and end of the trial. Use of gemfibrozil brought about increased HDL-cholesterol by 3.91% (P < 0.05) and reduced triglyceride and total cholesterol by 32.7% (P < 0.05) and 9.41% (P < 0.05), respectively. Applying Dill tablet for 2 months resulted in reduction of total cholesterol up to 18% (P < 0.05) and triglyceride by 7.38% (P < 0.05). However, circulating HDL-cholesterol was not affected by this treatment. In this study, gemfibrozil decreased triglyceride and increased HDL-cholesterol more than anethum (P < 0.05). Anethum decreased total cholesterol more than gemfibrozil (P < 0.05). Patients treated with anethum did not report any side effects. The results of this trial indicate that Dill might be beneficial for hypercholesterolemic and hypertriglycemic patients.

  15. A randomized trial of coenzyme Q10 in mitochondrial disorders.

    PubMed

    Glover, Elisa I; Martin, Joan; Maher, Amy; Thornhill, Rebecca E; Moran, Gerald R; Tarnopolsky, Mark A

    2010-11-01

    Case reports and open-label studies suggest that coenzyme Q(10) (CoQ(10)) treatment may have beneficial effects in mitochondrial disease patients; however, controlled trials are warranted to clinically prove its effectiveness. Thirty patients with mitochondrial cytopathy received 1200 mg/day CoQ(10) for 60 days in a randomized, double-blind, cross-over trial. Blood lactate, urinary markers of oxidative stress, body composition, activities of daily living, quality of life, forearm handgrip strength and oxygen desaturation, cycle exercise cardiorespiratory variables, and brain metabolites were measured. CoQ(10) treatment attenuated the rise in lactate after cycle ergometry, increased (∽1.93 ml) VO(2)/kg lean mass after 5 minutes of cycling (P < 0.005), and decreased gray matter choline-containing compounds (P < 0.05). Sixty days of moderate- to high-dose CoQ(10) treatment had minor effects on cycle exercise aerobic capacity and post-exercise lactate but did not affect other clinically relevant variables such as strength or resting lactate.

  16. Randomized trial of acupuncture for nicotine withdrawal symptoms.

    PubMed

    White, A R; Resch, K L; Ernst, E

    1998-11-09

    Acupuncture is frequently used for smoking cessation. Positive results from uncontrolled studies have not been supported by meta-analysis of controlled trials. One possible reason for this is that the optimal acupuncture technique was not applied or that the technique was not repeated sufficiently often. A randomized, sham-controlled trial was performed with 2 parallel treatment arms; the participant and the evaluator were unaware of which treatment was received. Seventy-six adults who wanted to stop smoking received either 100-Hz electroacupuncture with needles inserted into the appropriate point in each ear or a sham control procedure over the mastoid bone. Interventions were given on days 1, 3, and 7 of smoking cessation. Nicotine withdrawal symptoms were measured by visual analog scale scores recorded in a daily diary for 14 days; smoking cessation was confirmed objectively. There was no significant difference between the mean reduction of withdrawal symptom scores of the 2 groups from day 1 to day 14. Fifteen participants (39%) who received electroacupuncture and 16 participants (42%) who received a sham procedure were abstinent on day 14. This form of electroacupuncture is no more effective than placebo in reducing nicotine withdrawal symptoms.

  17. HealthLinks Randomized Controlled Trial: Design and Baseline Results

    PubMed Central

    Hammerback, Kristen; Allen, Claire L.; Parrish, Amanda T.; Chan, K. Gary; Kohn, Marlana J.; Teague, Sara; Beresford, Shirley A.A.; Helfrich, Christian D.; Harris, Jeffrey R.

    2016-01-01

    Small employers, especially those in low-wage industries, frequently lack the capacity and resources to implement evidence-based health promotion interventions without support and assistance. The purpose of this paper is to (a) describe the intervention design and study protocol of the HealthLinks Trial and (b) report baseline findings. This study is a three-arm randomized controlled trial testing the impact of the HealthLinks intervention on worksites’ adoption and implementation of evidence-based interventions. Group 1 will receive HealthLinks, Group 2 will receive HealthLinks plus wellness committees, and Group 3 will be a delayed control group. Seventy-eight employers are participating in the study; 3302 employees across the worksites participated in baseline data collection. Employers and employees will participate in follow-up surveys at one and two years after baseline to measure implementation (one year) and maintenance (two years) of HealthLinks interventions. Study outcomes will determine whether HealthLinks is an effective approach to increasing evidence-based health promotion in small, low-wage worksites and whether wellness committees are a capacity-building tool that increases HealthLinks’ effectiveness. PMID:26946121

  18. Teaching children to cross streets safely: a randomized, controlled trial.

    PubMed

    Schwebel, David C; McClure, Leslie A; Severson, Joan

    2014-07-01

    Child pedestrian injury is a global public health challenge. This randomized, controlled trial considered comparative efficacy of individualized streetside training, training in a virtual pedestrian environment, training using videos and Web sites, plus no-training control, to improve children's street-crossing ability. Pedestrian safety was evaluated among 231 7- and 8-year-olds using both streetside (field) and laboratory-based (virtual environment) trials before intervention group assignment, immediately posttraining, and 6 months posttraining. All training groups received 6 30-min sessions. Four outcomes assessed pedestrian safety: start delay (temporal lag before initiating crossing), hits/close calls (collisions/near-misses with vehicles in simulated crossings), attention to traffic (looks left and right, controlled for time), and missed opportunities (safe crossing opportunities that were missed). Results showed training in the virtual pedestrian environment and especially individualized streetside training resulted in safer pedestrian behavior postintervention and at follow-up. As examples, children trained streetside entered safe traffic gaps more quickly posttraining than control group children and children trained streetside or in the virtual environment had somewhat fewer hits/close calls in postintervention VR trials. Children showed minimal change in attention to traffic posttraining. Children trained with videos/websites showed minimal learning. Both individualized streetside training and training within virtual pedestrian environments may improve 7- and 8-year-olds' street-crossing safety. Individualized training has limitations of adult time and labor. Virtual environment training has limitations of accessibility and cost. Given the public health burden of child pedestrian injuries, future research should explore innovative strategies for effective training that can be broadly disseminated.

  19. Teaching Children to Cross Streets Safely: A Randomized Controlled Trial

    PubMed Central

    Schwebel, David C.; McClure, Leslie A.; Severson, Joan

    2014-01-01

    Objective Child pedestrian injury is a global public health challenge. This randomized controlled trial considered comparative efficacy of individualized streetside training, training in a virtual pedestrian environment, training using videos and websites, plus no-training control, to improve children’s street-crossing ability. Methods Pedestrian safety was evaluated among 231 seven- and eight-year-olds using both streetside (field) and laboratory-based (virtual environment) trials prior to intervention group assignment, immediately post-training, and six months post-training. All training groups received six 30-minute sessions. Four outcomes assessed pedestrian safety: start delay (temporal lag before initiating crossing), hits/close calls (collisions/near-misses with vehicles in simulated crossings), attention to traffic (looks left and right, controlled for time), and missed opportunities (safe crossing opportunities that were missed). Results Results showed training in the virtual pedestrian environment and especially individualized streetside training resulted in safer pedestrian behavior post-intervention and at follow-up. As examples, children trained streetside entered safe traffic gaps more quickly post-training than control group children and children trained streetside or in the virtual environment had somewhat fewer hits/close calls in post-intervention VR trials. Children showed minimal change in attention to traffic post-training. Children trained with videos/websites showed minimal learning. Conclusion Both individualized streetside training and training within virtual pedestrian environments may improve 7- and 8-year-olds’ street-crossing safety. Individualized training has limitations of adult time and labor. Virtual environment training has limitations of accessibility and cost. Given the public health burden of child pedestrian injuries, future research should explore innovative strategies for effective training that can be broadly

  20. Randomized clinical trials of constitutional acupuncture: a systematic review.

    PubMed

    Lee, Myeong Soo; Shin, Byung-Cheul; Choi, Sun-Mi; Kim, Jong Yeol

    2009-09-01

    The aim of this systematic review is to compile and critically evaluate the evidence from randomized clinical trials (RCTs) for the effectiveness of acupuncture using constitutional medicine compared to standard acupuncture. Ten databases were searched through to December 2008 without language restrictions. We also hand-searched nine Korean journals of oriental medicine. We included prospective RCTs of any form of acupuncture with or without electrical stimulation. The included trials had to investigate constitutional medicine. There were no restrictions on population characteristics. Forty-one relevant studies were identified, and three RCTs were included. The methodological quality of the trials was variable. One RCT found Sasang constitutional acupuncture to be superior to standard acupuncture in terms of the Unified PD Rating Scale and freezing gate in Parkinson's disease (PD). Another two RCTs reported favorable effects of eight constitutional acupuncture on pain reduction in patients with herniated nucleus pulposi and knee osteoarthritis. Meta-analysis demonstrated positive results for eight constitutional acupuncture compared to standard acupuncture on pain reduction (weighted mean difference: 10 cm VAS, 1.69, 95% CI 0.85-2.54, P < 0.0001; heterogeneity: tau(2) = 0.00, chi(2) = 0.00, P = 0.96, I(2) = 0%). Our results provide suggestive evidence for the effectiveness of constitutional acupuncture in treating pain conditions compared to standard acupuncture. However, the total number of RCTs and the total sample size included in our analysis were too small to draw definite conclusions. Future RCTs should assess larger patient samples with longer treatment periods and appropriate controls.

  1. Randomized trial of TAS-102 for refractory metastatic colorectal cancer.

    PubMed

    Mayer, Robert J; Van Cutsem, Eric; Falcone, Alfredo; Yoshino, Takayuki; Garcia-Carbonero, Rocio; Mizunuma, Nobuyuki; Yamazaki, Kentaro; Shimada, Yasuhiro; Tabernero, Josep; Komatsu, Yoshito; Sobrero, Alberto; Boucher, Eveline; Peeters, Marc; Tran, Ben; Lenz, Heinz-Josef; Zaniboni, Alberto; Hochster, Howard; Cleary, James M; Prenen, Hans; Benedetti, Fabio; Mizuguchi, Hirokazu; Makris, Lukas; Ito, Masanobu; Ohtsu, Atsushi

    2015-05-14

    Early clinical trials conducted primarily in Japan have shown that TAS-102, an oral agent that combines trifluridine and tipiracil hydrochloride, was effective in the treatment of refractory colorectal cancer. We conducted a phase 3 trial to further assess the efficacy and safety of TAS-102 in a global population of such patients. In this double-blind study, we randomly assigned 800 patients, in a 2:1 ratio, to receive TAS-102 or placebo. The primary end point was overall survival. The median overall survival improved from 5.3 months with placebo to 7.1 months with TAS-102, and the hazard ratio for death in the TAS-102 group versus the placebo group was 0.68 (95% confidence interval [CI], 0.58 to 0.81; P<0.001). The most frequently observed clinically significant adverse events associated with TAS-102 were neutropenia, which occurred in 38% of those treated, and leukopenia, which occurred in 21%; 4% of the patients who received TAS-102 had febrile neutropenia, and one death related to TAS-102 was reported. The median time to worsening performance status (a change in Eastern Cooperative Oncology Group performance status [on a scale of 0 to 5, with 0 indicating no symptoms and higher numbers indicating increasing degrees of disability] from 0 or 1 to 2 or more) was 5.7 months with TAS-102 versus 4.0 months with placebo (hazard ratio, 0.66; 95% CI, 0.56 to 0.78; P<0.001). In patients with refractory colorectal cancer, TAS-102, as compared with placebo, was associated with a significant improvement in overall survival. (Funded by Taiho Oncology-Taiho Pharmaceutical; RECOURSE ClinicalTrials.gov number, NCT01607957.).

  2. Aerobic exercise for Alzheimer's disease: A randomized controlled pilot trial

    PubMed Central

    Van Sciver, Angela; Mahnken, Jonathan D.; Honea, Robyn A.; Brooks, William M.; Billinger, Sandra A.; Swerdlow, Russell H.; Burns, Jeffrey M.

    2017-01-01

    Background There is increasing interest in the role of physical exercise as a therapeutic strategy for individuals with Alzheimer’s disease (AD). We assessed the effect of 26 weeks (6 months) of a supervised aerobic exercise program on memory, executive function, functional ability and depression in early AD. Methods and findings This study was a 26-week randomized controlled trial comparing the effects of 150 minutes per week of aerobic exercise vs. non-aerobic stretching and toning control intervention in individuals with early AD. A total of 76 well-characterized older adults with probable AD (mean age 72.9 [7.7]) were enrolled and 68 participants completed the study. Exercise was conducted with supervision and monitoring by trained exercise specialists. Neuropsychological tests and surveys were conducted at baseline,13, and 26 weeks to assess memory and executive function composite scores, functional ability (Disability Assessment for Dementia), and depressive symptoms (Cornell Scale for Depression in Dementia). Cardiorespiratory fitness testing and brain MRI was performed at baseline and 26 weeks. Aerobic exercise was associated with a modest gain in functional ability (Disability Assessment for Dementia) compared to individuals in the ST group (X2 = 8.2, p = 0.02). There was no clear effect of intervention on other primary outcome measures of Memory, Executive Function, or depressive symptoms. However, secondary analyses revealed that change in cardiorespiratory fitness was positively correlated with change in memory performance and bilateral hippocampal volume. Conclusions Aerobic exercise in early AD is associated with benefits in functional ability. Exercise-related gains in cardiorespiratory fitness were associated with improved memory performance and reduced hippocampal atrophy, suggesting cardiorespiratory fitness gains may be important in driving brain benefits. Trial registration ClinicalTrials.gov NCT01128361 PMID:28187125

  3. AcuTrials®: an online database of randomized controlled trials and systematic reviews of acupuncture

    PubMed Central

    2013-01-01

    Background The growing quantity of Complementary and Alternative Medicine literature requires databases enabled with increasingly powerful search capabilities. To address this need in the area of acupuncture research, a bibliographic database of randomized controlled trials (RCTs) and systematic reviews called AcuTrials® has been developed by the Oregon College of Oriental Medicine. AcuTrials® introduces a comprehensive keyword thesaurus that categorizes details of treatment protocols and research design to an extent not currently available in MEDLINE or other databases. Description AcuTrials®, which went live in January of 2010 and is updated monthly, currently contains over 1250 articles from more than 300 journals. Articles included are English language RCTs and systematic reviews that report on medical conditions in human subjects treated by needle acupuncture. Study details are indexed by 14 key domains, such as acupuncture style and needling protocol, to create an acupuncture-relevant, searchable keyword catalogue. Keywords follow the National Library of Medicine (NLM) MeSH terminology when possible, and new keywords were created in cases where no appropriate MeSH terms were available. The resulting keyword catalogue enables users to perform sensitive, targeted searches for particular aspects of acupuncture treatment and research design. Conclusions AcuTrials® provides an extensive and innovative keyword catalogue of acupuncture research, allowing users to efficiently navigate, locate and assess the evidence base in ways not currently possible with other databases. By providing a more powerful suite of search options, the AcuTrials® database has the potential to enhance the accessibility and quality of acupuncture research. PMID:23866767

  4. Effects of auriculotherapy on labour pain: a randomized clinical trial.

    PubMed

    Mafetoni, Reginaldo Roque; Shimo, Antonieta Keiko Kakuda

    2016-01-01

    Assessing the effects of auriculotherapy in pain control and its outcomes on the duration of labour. This is a randomized, controlled, double-blind trial with preliminary data. Thirty pregnant women with gestational age ≥ 37 weeks, cervical dilatation ≥ 4 cm and two or more contractions in 10 minutes were selected and randomly divided into three groups: auriculotherapy, placebo and control. Auriculotherapy was applied using crystal beads on four strategic points. No statistical significance was found between the groups with regard to pain; however, the women from the auriculotherapy group had lower intensity and less perception of pain at 30, 60 and 120 minutes of treatment. The average duration of labour was shorter in the auriculotherapy group (248.7 versus placebo 414.8 versus control 296.3 minutes); caesarean section rates were higher in the placebo group (50%) and the same in the other groups (10%). Mothers who received auriculotherapy presented a tendency for greater pain control and shorter labour duration; however, caesarean section rates in this group were similar to the control group. This trial precedes a larger study in progress. Registration of Brazilian Clinical Trials: RBR-47hhbj. Avaliar os efeitos da auriculoterapia no controle da dor e seus desfechos na duração do trabalho de parto. Trata-se de um ensaio controlado, randomizado e duplo-cego, com dados preliminares. Foram selecionadas 30 parturientes com idade gestacional ≥ 37 semanas, dilatação cervical ≥ 4 cm e duas ou mais contrações em 10 minutos, divididas aleatoriamente em três grupos: auriculoterapia, placebo ou controle. A auriculoterapia foi aplicada com microesferas de cristais em quatro pontos estratégicos. Não houve significância estatística entre os grupos com relação à dor; no entanto, as mulheres do grupo de auriculoterapia, apresentaram menor intensidade e menor percepção da dor aos 30, 60 e 120 minutos do tratamento. A média de duração do trabalho de

  5. Rehabilitation in advanced, progressive, recurrent cancer: a randomized controlled trial.

    PubMed

    Jones, Louise; Fitzgerald, Gail; Leurent, Baptiste; Round, Jeffrey; Eades, Jane; Davis, Sarah; Gishen, Faye; Holman, Amanda; Hopkins, Katherine; Tookman, Adrian

    2013-09-01

    Two million people across the U.K. are living with cancer, often experienced as a long-term condition. They may have unmet needs after active treatment. Rehabilitation aims to address these needs, maximize psychological and physical function, and enable minimum dependency regardless of life expectancy. We aimed to test, in a randomized controlled trial, the clinical and cost effectiveness of a rehabilitation intervention for patients with advanced, recurrent cancer. We conducted a two-arm, wait-list control, randomized trial of a complex rehabilitation intervention delivered by a hospice-based multidisciplinary team vs. usual care for active, progressive, recurrent hematological and breast malignancies, with a follow-up at three months. The primary outcome was the psychological subscale of the Supportive Care Needs Survey (SCNS). Secondary outcomes were other domains of the SCNS, psychological status, continuity of care, quality of life, and resource use. Forty-one participants were enrolled and 36 completed the trial. The primary outcome was significantly lower in the intervention arm (adjusted difference -16.8, 95% CI -28.34 to -5.3; P = 0.006). The SCNS physical and patient care subscales (-14.2, 95% CI -26.2 to -2.2; P = 0.02 and -7.4, 95% CI -13.7 to -1.1; P = 0.02, respectively) and self-reported health state (12.8, 95% CI 3.2 to 22.4; P = 0.01) also differed significantly. The incremental cost-effectiveness ratio was £19,390 per quality-adjusted life year. This intervention significantly reduced the unmet needs of cancer survivors and it is likely that it is cost-effective. Despite small numbers, the main effect size was robust. We recommend implementation alongside evaluation in wider clinical settings and patient populations. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

  6. A randomized prospective multicenter trial of a novel vascular sealant.

    PubMed

    Stone, William M; Cull, David L; Money, Samuel R

    2012-11-01

    Increasing use of anticoagulant medications, particularly antiplatelet therapies, can increase the difficulty in obtaining adequate suture line hemostasis. Multiple vascular sealants have been used as adjuncts to surgical procedures, but none of them have been universally successful. The aim of this study was to evaluate the safety and effectiveness of a new prophylactic vascular sealant in arterial surgery. A randomized prospective multi-institutional trial was undertaken comparing ArterX Vascular Sealant (AVS) with Gelfoam Plus during open arterial reconstruction. Three hundred thirty-one anastomotic sites in 217 patients were randomized. One hundred one of 167 (60.5%) anastomotic sites in the AVS group achieved immediate hemostasis compared with 65 of 164 (39.6%) in the control group (P = 0.001). In anastomoses with polytetrafluoroethylene grafts, 105 of 167 (62.5%) in the AVS group achieved immediate hemostasis compared with 56 of 164 (34.0%) in the control group (P < 0.001). No significant differences were noted in morbidity or mortality. Operative time was significantly less in the AVS group compared with the control group (3.2 vs. 3.8 hours, P < 0.01). Use of AVS results in superior hemostatic effectiveness compared with Gelfoam Plus, with no difference in safety. Although no cost analysis was performed, cost savings likely resulted from significantly decreased operative time. Copyright © 2012 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.

  7. Postoperative pain relief following hysterectomy: A randomized controlled trial

    PubMed Central

    Raghvendra, K. P.; Thapa, Deepak; Mitra, Sukanya; Ahuja, Vanita; Gombar, Satinder; Huria, Anju

    2016-01-01

    Background: Women experience moderate to severe postoperative pain following total abdominal hysterectomy (TAH). The transversus abdominis plane (TAP) block is a new modality for providing postoperative pain relief in these patients. Materials and Methods: The present study was a single center, prospective randomized trial. After the Institutional Ethics Committee approval and informed consent, patients were randomized to either epidural group: Epidural block placement + general anesthesia (GA) or TAP group: Single shot TAP block + GA. Patients in both the groups received standard general anesthetic technique and intravenous tramadol patient-controlled analgesia in the postoperative period. Patients were monitored for tramadol consumption, visual analog scale (VAS) both at rest and on coughing, hemodynamics, and side effects at 0, 2, 4, 6, 8, 12, and 24 h postoperatively. Results: The total consumption of tramadol in 24 h was greater in TAP group as compared to epidural group (68.8 [25.5] vs. 5.3 [11.6] mg, P < 0.001). The VAS scores at rest and on coughing were higher in TAP group as compared to the epidural group at 6, 8, 12, and 24 h postoperatively (P < 0.05). None of the patients in either group had any adverse effects. Conclusion: Epidural analgesia provided greater tramadol-sparing effect with superior analgesia postoperatively as compared to TAP block in patients up to 24 h following TAH. PMID:27499592

  8. The Effectiveness of Propolis on Gingivitis: A Randomized Controlled Trial

    PubMed Central

    Paulino, Niraldo; Nör, Jacques E.; Moreira, Alexandre

    2014-01-01

    Abstract Background: A randomized, double-blind, controlled clinical trial was conducted to evaluate the effectiveness of a propolis rinse on induced gingivitis by using the co-twin study design. Methods: Twenty-one twin pairs (n=42) were enrolled in a gingivitis study with oral hygiene promotion (14 days) and gingivitis induction (21 days). During the gingivitis induction phase, one member of the twin pair was randomly assigned to a 2% typified propolis rinse, and the other was assigned a color-matched 0.05% sodium fluoride plus 0.05% cetylpyridinium chloride rinse (positive control). Patients rinsed twice daily with 20 mL for 30 seconds for 21 days. Gingivitis was measured on days −14 (baseline), 0 (after hygiene phase), and 21 (after no-hygiene phase) by using the Papillary Bleeding Score (PBS) and by standard digital imaging of the gum tissues (G-parameter). Results: The 38 persons who completed the study (age 13–22 years) were well balanced according to PBS at baseline and G-parameter after the initial hygiene phase. After 21 days without oral hygiene, the propolis rinse and positive control rinse groups did not differ significantly for average PBS measurements or G-parameter. Conclusions: Use of a 2% typified propolis rinse was equivalent to a positive control rinse during a 21-day no-hygiene period. PMID:25380344

  9. Improving pediatric prevention via the internet: a randomized, controlled trial.

    PubMed

    Christakis, Dimitri A; Zimmerman, Frederick J; Rivara, Frederick P; Ebel, Beth

    2006-09-01

    Innovations to improve the delivery of pediatric preventive care are needed. We enrolled children, 0 to 11 years of age, into a factorial, randomized, controlled trial of a tailored, evidence-based, Web site (MyHealthyChild) that provided information on prevention topics before a scheduled well-child visit. There were 2 components of the intervention, namely, parental Web content and provider notification. Parental Web content provided information to parents about prevention topics; provider notification communicated to physicians topics that were of interest to parents. We assigned 887 children randomly to 4 groups (usual care, content only, content and notification, or notification only). Outcomes were determined with telephone follow-up surveys conducted 2 to 4 weeks after the visit. Poisson regression analysis was used to determine the independent effects of each intervention on the number of topics discussed and the number of preventive practices implemented. Parents in the notification/content group and in the notification-only group reported discussing more MyHealthyChild topics with their provider. Parents in the notification/content group and in the content-only group reported implementing more MyHealthyChild topic suggestions (such as use of a safety device). A Web-based intervention can activate parents to discuss prevention topics with their child's provider. Delivery of tailored content can promote preventive practices.

  10. Psychosocial Telephone Intervention for Dementia Caregivers: A Randomized, Controlled Trial

    PubMed Central

    Tremont, Geoffrey; Davis, Jennifer D.; Papandonatos, George D.; Ott, Brian R.; Fortinsky, Richard H.; Gozalo, Pedro; Yue, Mun Sang; Bryant, Kimberly; Christine, Grover; Bishop, Duane S.

    2014-01-01

    Background Identifying effective and accessible interventions for dementia caregivers is critical as dementia prevalence increases. Objective Examine the effects of a telephone-based intervention on caregiver well-being. Design Randomized, controlled trial. Setting Academic medical center. Participants 250 distressed, family, dementia caregivers. Intervention Caregivers randomized to receive 16 telephone contacts over 6 months of either the Family Intervention: Telephone Tracking–Caregiver (FITT-C) or Telephone Support (TS). Outcome Primary outcome variables were family caregivers’ depressive symptoms, burden, and reactions to care recipients’ behavior problems at 6 months. Results The FITT-C intervention resulted in significantly improved caregiver depressive symptoms (p = 0.003; 27% net improvement) and less severe reactions to care-recipient depressive behaviors (p = 0.009; 29% net improvement) compared to the control condition (TS). Conclusion An entirely telephone-based intervention improves caregivers’ depressive symptoms and reactions to behavior problems in the care recipient and is comparable to reported results of face-to-face interventions. PMID:25074341

  11. Design of Sequentially Randomized Trials for Testing Adaptive Treatment Strategies

    PubMed Central

    Ogbagaber, Semhar B.; Karp, Jordan; Wahed, Abdus S.

    2016-01-01

    An adaptive treatment strategy (ATS) is an outcome-guided algorithm that allows personalized treatment of complex diseases based on patients’ disease status and treatment history. Conditions such as AIDS, depression, and cancer usually require several stages of treatment due to the chronic, multifactorial nature of illness progression and management. Sequential multiple assignment randomized (SMAR) designs permit simultaneous inference about multiple ATSs, where patients are sequentially randomized to treatments at different stages depending upon response status. The purpose of the article is to develop a sample size formula to ensure adequate power for comparing two or more ATSs. Based on a Wald-type statistic for comparing multiple ATSs with a continuous endpoint, we develop a sample size formula and test it through simulation studies. We show via simulation that the proposed sample size formula maintains the nominal power. The proposed sample size formula is not applicable to designs with time-to-event endpoints but the formula will be useful for practitioners while designing SMAR trials to compare adaptive treatment strategies. PMID:26412033

  12. Motivational interviewing and intimate partner violence: a randomized trial.

    PubMed

    Saftlas, Audrey F; Harland, Karisa K; Wallis, Anne B; Cavanaugh, Joseph; Dickey, Penny; Peek-Asa, Corinne

    2014-02-01

    To determine if motivational interviewing (MI) improves self-efficacy (primary outcome), depressive symptoms (secondary outcome), and stage-of-readiness-to-change (secondary outcome) among women in abusive relationships. Randomized controlled trial among women who experienced intimate partner violence in a current relationship over the past 12 months. Subjects were recruited from two family planning clinics (December 2007 to May 2010). The intervention included an initial face-to-face session and three telephone sessions administered 1-, 2-, and 4-months postenrollment, each using MI to identify personal goals. Controls were referred to community-based resources. Outcomes were measured by self-administered questionnaires before randomization and 6 months later. Modified intent-to-treat analyses of completed participants were conducted using multivariate analysis of variance for continuous outcomes and polytomous logistic regression for categorical outcomes. Three hundred six eligible women were enrolled (recruitment rate = 64%); 204 completed the 6-month follow-up (completion rate = 67%). Depressive symptoms decreased to a greater extent in MI than referral women (P = .07). Self-efficacy and stage-of-readiness-to-change increased more in MI than referral women, but these differences were not statistically significant. With a lower than projected sample size, our findings did not achieve statistical significance at the 5% level but suggest a beneficial effect of the MI intervention on reducing depressive symptoms. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. The effectiveness of propolis on gingivitis: a randomized controlled trial.

    PubMed

    Bretz, Walter A; Paulino, Niraldo; Nör, Jacques E; Moreira, Alexandre

    2014-12-01

    A randomized, double-blind, controlled clinical trial was conducted to evaluate the effectiveness of a propolis rinse on induced gingivitis by using the co-twin study design. Twenty-one twin pairs (n=42) were enrolled in a gingivitis study with oral hygiene promotion (14 days) and gingivitis induction (21 days). During the gingivitis induction phase, one member of the twin pair was randomly assigned to a 2% typified propolis rinse, and the other was assigned a color-matched 0.05% sodium fluoride plus 0.05% cetylpyridinium chloride rinse (positive control). Patients rinsed twice daily with 20 mL for 30 seconds for 21 days. Gingivitis was measured on days -14 (baseline), 0 (after hygiene phase), and 21 (after no-hygiene phase) by using the Papillary Bleeding Score (PBS) and by standard digital imaging of the gum tissues (G-parameter). The 38 persons who completed the study (age 13-22 years) were well balanced according to PBS at baseline and G-parameter after the initial hygiene phase. After 21 days without oral hygiene, the propolis rinse and positive control rinse groups did not differ significantly for average PBS measurements or G-parameter. Use of a 2% typified propolis rinse was equivalent to a positive control rinse during a 21-day no-hygiene period.

  14. A randomized controlled trial of home tooth-whitening products.

    PubMed

    Lo, Edward C M; Wong, Anthony H H; McGrath, Colman

    2007-10-01

    To evaluate the effectiveness of two marketed home tooth-whitening products. A randomized controlled clinical trial involving 87 adults who were randomly allocated into one of three groups: (1) 6% hydrogen peroxide whitening strips, (2) 18% carbamide peroxide whitening gel, and (3) a placebo (fluoride toothpaste) control group. Subjects were instructed individually and then used the given product daily for 2 consecutive weeks. Color was determined in brightness (L*), yellowness (b*) and redness (a*) [color space] at baseline and 8 weeks after dispensing the product by employing a high resolution digital camera (Fuji HC1000 CCD) to image the subject's anterior maxillary teeth under standard polarized lighting conditions. The subjects also completed a questionnaire on self-satisfaction with the treatment outcome. One-way ANOVA (Bonferroni test) demonstrated significant differences in color between the three groups with changes in brightness (L*, P< 0.001), yellowness (b*, P< 0.001) and redness (a*, P < 0.001). Changes in L* a* b* was greatest among those who used the 6% hydrogen peroxide whitening strips. Subjects in the whitening strip group also rated that product significantly (P < 0.01) more favorably than other groups with respect to the amount of whiteness improvement, as well as whitening satisfaction and overall impression while there is no significant difference between the whitening gel and the placebo groups.

  15. Nebulized Magnesium Sulfate in Acute Bronchiolitis: A Randomized Controlled Trial.

    PubMed

    Modaresi, Mohammad Reza; Faghihinia, Jamal; Kelishadi, Roya; Reisi, Mohsen; Mirlohi, Shahrokh; Pajhang, Farhad; Sadeghian, Majid

    2015-09-01

    To assess the efficacy of nebulized magnesium sulfate as a bronchodilator in infants hospitalized with acute bronchiolitis. This three-center double masked randomized clinical trial comprised 120 children with moderate to severe bronchiolitis. They were randomly assigned into two groups: the first group was treated with nebulized magnesium sulfate (40 mg/kg) and nebulized epinephrine (0.1 ml/kg) and the second group (control) was treated with nebulized epinephrine (0.1 ml/kg). The primary outcome was the length of hospital stay. The use of oxygen, temperature, oxygen saturation (SPO2), pulse rate (PR), respiratory rate (RR) and respiratory distress assessment instrument (RDAI) score were measured in the beginning of the study and during hospitalization. The mean (SD) age of 120 infants was 5.1(± 2.6) mo and 60% were boys. The length of hospital stay was not different between the two groups (P > 0.01). Use of oxygen supplementation, SPO2 and vital signs were similar in the two groups. Improvement in RDAI score was significantly better in infants treated with nebulized magnesium sulfate than in the other group (P 0.01). Thus, in infants with acute bronchiolitis, the effect of nebulized magnesium sulfate is comparable to nebulized epinephrine. However nebulized magnesium sulfate can improve the clinical score so it may have additive effect to reduce symptoms during hospitalization.

  16. Metoclopramide to augment lactation, does it work? A randomized trial.

    PubMed

    Fife, Shannon; Gill, Prabhcharan; Hopkins, Michael; Angello, Carol; Boswell, Sue; Nelson, Karl M

    2011-11-01

    The objective of this study was to investigate the efficacy of metoclopramide on augmentation of milk production in mothers of premature newborns. This was a randomized, double-blind, placebo-controlled trial. Women who delivered at ≤34 weeks of gestation, with no prior breastfeeding experience, singleton pregnancy, and no contraindications to using metoclopramide were eligible for entry. Twenty-five women were randomly assigned to receive 10 mg of metoclopramide or placebo three times daily for 8 days starting within 36 h of birth. Certified lactation nurses provided breastfeeding education. Breast milk expressed at each pumping session over the 8 days of treatment was recorded. Data from 18 patients were available for analysis. Milk production in both groups increased rapidly during the first 4 days and then more gradually to an average for the last 4 days of 633 ± 168 (9) ml/day [mean ± SEM (n)] for the placebo group and 459 ± 91 (10) ml/day for the metoclopramide group. Analysis with a repeated-measures ANOVA indicated a significant increase in milk production during the 8-day measurement period [within subjects p < 0.001]; however, there was no significant difference in milk production between the two groups [between subjects p = 0.427]. Side effects were similar between groups. In mothers with preterm babies, metoclopramide treatment does not augment (sample size had 80% power for detection of 50% difference) the breast milk production. Maternal interest, education, and support are recognized as mainstay in accomplishing successful lactation.

  17. Psychosocial telephone intervention for dementia caregivers: A randomized, controlled trial.

    PubMed

    Tremont, Geoffrey; Davis, Jennifer D; Papandonatos, George D; Ott, Brian R; Fortinsky, Richard H; Gozalo, Pedro; Yue, Mun Sang; Bryant, Kimberly; Grover, Christine; Bishop, Duane S

    2015-05-01

    Identifying effective and accessible interventions for dementia caregivers is critical as dementia prevalence increases. Examine the effects of a telephone-based intervention on caregiver well-being. Randomized, controlled trial. Academic medical center. Two hundred and fifty distressed, family, dementia caregivers. Caregivers randomized to receive 16 telephone contacts over 6 months of either the Family Intervention: Telephone Tracking-Caregiver (FITT-C) or Telephone Support (TS). Primary outcome variables were family caregivers' depressive symptoms, burden, and reactions to care recipients' behavior problems at 6 months. The FITT-C intervention resulted in significantly improved caregiver depressive symptoms (P = .003; 27% net improvement) and less severe reactions to care-recipient depressive behaviors (P = .009; 29% net improvement) compared with the control condition (TS). An entirely telephone-based intervention improves caregivers' depressive symptoms and reactions to behavior problems in the care recipient and is comparable with reported results of face-to-face interventions. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  18. Online psychoeducational support for infertile women: a randomized controlled trial

    PubMed Central

    Cousineau, Tara M.; Green, Traci C.; Corsini, Evelyn; Seibring, A; Showstack, Marianne T.; Applegarth, Linda; Davidson, Marie; Perloe, Mark

    2008-01-01

    BACKGROUND The study goal was to develop and test the effectiveness of a brief online education and support program for female infertility patients. METHODS A randomized-controlled trial was conducted. Using a Solomon-four group design, 190 female patients were recruited from three US fertility centers and were randomized into two experimental and two no-treatment control groups. The psychological outcomes assessed included infertility distress, infertility self-efficacy, decisional conflict, marital cohesion and coping style. Program dosage and satisfaction were also assessed at four weeks follow-up. RESULTS Women exposed to the online program significantly improved in the area of social concerns (P = 0.038) related to infertility distress, and felt more informed about a medical decision with which they were contending (P = 0.037). Trends were observed for decreased global stress (P = 0.10), sexual concerns (P = 0.059), distress related to child-free living (P = 0.063), increased infertility self-efficacy (P = 0.067) and decision making clarity (P = 0.079). A dosage response was observed in the experimental groups for women who spent >60 min online for decreased global stress (P = 0.028) and increased self efficacy (P = 0.024). CONCLUSIONS This evidence-based eHealth program for women experiencing infertility suggests that a web-based patient education intervention can have beneficial effects in several psychological domains and may be a cost effective resource for fertility practices. PMID:18089552

  19. Extrinsic stain removal with a toothpowder: A randomized controlled trial

    PubMed Central

    Khan, Muhammad Khalil; Bokhari, Syed Akhtar Hussain; Haleem, Abdul; Kareem, Abdul; Khan, Ayyaz Ali; Hosein, Tasleem; Khan, Muhammad Usama

    2014-01-01

    Objectives The efficacy of a commercially available toothpowder was compared with toothpaste in removing extrinsic dental stains. Methods In this single-blind, randomized controlled trial, 77 volunteers were included from a residential professional college. All study subjects (control toothpaste users and test toothpowder users) plaque control measures. All study subjects were instructed to rinse with 5 ml 0.12% chlorhexidine mouthwash for 1 minute, twice and one cup of double tea bag solution three times daily for three weeks. Subjects were randomized into test (n=36) and control (n=36) groups. Toothpaste (control) and toothpowder (test) was used for two weeks to see the effects on removing stains on the labial surfaces of 12 anterior teeth. For measuring dental extrinsic stains Lobene Stain Index (SI) was used. Results The amount of stain following the use of toothpaste and toothpowder was more controlled with the experimental toothpowder. For all sites combined, there was evidence that the experimental toothpowder was significantly superior to toothpaste in reducing stain area (p<.001), stain intensity (p<.001) and composite/product (area × intensity) (p<.001). Conclusion Stain removing efficacy of toothpowder was significantly higher as compared with toothpaste. A toothpowder may be expected to be of benefit in controlling and removing extrinsic dental staining. PMID:25505862

  20. Design Issues in Randomized Clinical Trials of Maintenance Therapies

    PubMed Central

    Little, Richard F.; Korn, Edward L.

    2015-01-01

    A potential therapeutic strategy for patients who respond (or have stable disease) on a fixed-duration induction therapy is to receive maintenance therapy, typically given for a prolonged period of time. To enable patients and clinicians to make informed treatment decisions, the designs of phase III randomized clinical trials (RCTs) assessing maintenance strategies need to be such that their results will provide clear assessment of the relevant risks and benefits of these strategies. We review the key aspects of maintenance RCT designs. Important design considerations include choice of first-line and second-line therapies, minimizing between-arm differences in follow-up schedules, and choice of the primary endpoint. In order to change clinical practice, RCTs should be designed to accurately isolate and quantify the clinical benefit of maintenance as compared with the standard approach of fixed-duration induction followed by the second-line treatment at progression. To accomplish this, RCTs need to utilize an overall survival (or quality of life) endpoint or, in settings where this is not feasible, endpoints that incorporate the effects of the subsequent line of therapy (eg, time from randomization to second progression or death). Toxicity and symptom information over both the study treatment (maintenance) and the second-line treatment should also be collected and reported. PMID:26286730

  1. Prospective randomized clinical trial: single and weekly viscosupplementation

    PubMed Central

    Zóboli, Alejandro Agustin Carri; de Rezende, Márcia Uchôa; de Campos, Gustavo Constantino; Pasqualin, Thiago; Frucchi, Renato; de Camargo, Olavo Pires

    2013-01-01

    OBJECTIVE: To compare two different dosages of an intermediate molecular weight sodium hyaluronate (HA) (Osteonil®-TRB Pharma) assessing whether a single 6 ml application of this HA has the same effectiveness as the classical three-weekly 2 ml dose. METHODS: 108 patients with knee osteoarthritis were randomized into two groups of 54 patients each. The groups were designated "single" (S) and "weekly" (W). Patients in group S underwent a viscosupplementation procedure by application of only 6 ml of sodium hyaluronate and 1 ml triamcinolone hexacetonide. Patients in group W underwent the procedure of viscosupplementation through three applications with 2 ml sodium hyaluronate with a week interval between them, and the first application was also performed with the infiltration of 1 ml (20 mg) of Triamcinolone Hexacetonide. Both groups were assessed before, at one month and three months after application, by responding to the WOMAC, Lequesne, IKDC and VAS questionnaires. RESULTS: There was no statistical difference between the single application of 6 ml of sodium hyaluronate and classic application with three weekly injections. However, only the classical regime showed statistically significant improvement in baseline pain (WOMAC pain and VAS). CONCLUSION: Our results suggest that both application schemes improve application function, but the three-weekly regimen of 2 ml was more effective in reducing pain. Level of Evidence I, Prospective Randomized, Clinical Trial. PMID:24453681

  2. Diabetes Prevention in Hispanics: Report From a Randomized Controlled Trial

    PubMed Central

    Carosso, Elizabeth; Mariscal, Norma; Islas, Ilda; Ibarra, Genoveva; Holte, Sarah; Copeland, Wade; Linde, Sandra; Thompson, Beti

    2014-01-01

    Introduction Hispanics are at increased risk of developing type 2 diabetes. Lifestyle interventions are effective in preventing diabetes and restoring glucose regulation. Methods We recruited Hispanic men and women (N = 320) who were residents of the Lower Yakima Valley, Washington, aged 18 years or older with hemoglobin A1c (HbA1c) levels higher than 6% to a parallel 2-arm randomized-controlled trial conducted from 2008 through 2012. The trial compared participants in the intervention arm, who received an immediate educational curriculum (n = 166), to participants in the control arm, who received a delayed educational curriculum (n = 154). The home-based curriculum consisted of 5 sessions led by community health workers and was designed to inform participants about diabetes, diabetes treatment, and healthy dietary and physical activity behaviors. Participants were randomly assigned to the intervention and control arms, and analysts were blinded as to participant arm. We evaluated intervention effects on HbA1c levels; frequency (times per week) of fruit and vegetable consumption; and frequency (times per week) of mild, moderate, and strenuous leisure-time physical activity. At baseline, 3 months, and 6 months after randomization, participants completed a questionnaire and provided a blood sample. Analysts were blinded to intervention arm. Results The immediate intervention group (−0.64% [standard error (SE) 0.10]) showed a significant improvement in HbA1c scores (–37.5%, P = .04) compared with the delayed intervention group (–0.44%, P = .14). No significant changes were seen for dietary end points or changes in physical activity. We did observe a trend of greater increases in frequency of moderate and vigorous physical activity and a smaller increase in mild physical activity in the immediate intervention group than in the delayed intervention group. Conclusion This home-based intervention delivered by CHWs was associated with a clinically and statistically

  3. A Randomized Trial of Doxycycline for Mansonella perstans Infection

    PubMed Central

    Coulibaly, Yaya I.; Dembele, Benoit; Diallo, Abdallah A.; Lipner, Ettie M.; Doumbia, Salif S.; Coulibaly, Siaka Y.; Konate, Siaka; Diallo, Dapa A.; Yalcouye, Daniel; Kubofcik, Joseph; Doumbo, Ogobara K.; Traore, Abdel K.; Keita, Adama D.; Fay, Michael P.; Traore, Sekou F.; Nutman, Thomas B.; Klion, Amy D.

    2012-01-01

    Background Mansonella perstans infection is common in areas of Africa where Wuchereria bancrofti, a causative agent of lymphatic filariasis, is endemic. M. perstans is refractory to standard antifilarial therapies. The recent discovery of bacterial endosymbionts (e.g., wolbachia) in most filarial species, including M. perstans, provides new therapeutic options for reducing microfilaremia. Methods In an open-label, randomized trial, we recruited subjects with M. perstans microfilaremia, with or without concomitant W. bancrofti infection, from four villages in Mali and randomly assigned them to receive doxycycline, at a dose of 200 mg daily for 6 weeks (106 subjects), or no treatment (110). At 6 months, subjects who were co-infected with W. bancrofti underwent a second random assignment, to treatment with a single dose of albendazole (400 mg) and ivermectin (150 μg per kilogram of body weight) or no treatment. Subjects were monitored daily during the first 6-week study period for adverse events. M. perstans and W. bancrofti microfilarial levels were assessed at 6, 12, and 36 months. Results At 12 months, 67 of 69 subjects who had received treatment with doxycycline only (97%) had no detectable M. perstans microfilariae per 60 μl of blood, as compared with 10 of 63 subjects who had received no treatment (16%) (relative risk, 6.18; 95% confidence interval, 3.63 to 11.89; P<0.001). At 36 months, M. perstans microfilaremia remained suppressed in 48 of 64 subjects who had received treatment with doxycycline only (75%), a finding that was consistent with a macrofilaricidal effect of doxycycline. Vomiting was more frequent in the doxycycline-treated group than in the untreated group (17% vs. 4%). Conclusions These results are consistent with previous findings that M. perstans harbors the intracellular endosymbiont, wolbachia, and suggest that doxycycline is an effective therapy for M. perstans infection. PMID:19812401

  4. Randomized clinical trial of deep brain stimulation for poststroke pain.

    PubMed

    Lempka, Scott F; Malone, Donald A; Hu, Bo; Baker, Kenneth B; Wyant, Alexandria; Ozinga, John G; Plow, Ela B; Pandya, Mayur; Kubu, Cynthia S; Ford, Paul J; Machado, Andre G

    2017-05-01

    The experience with deep brain stimulation (DBS) for pain is largely based on uncontrolled studies targeting the somatosensory pathways, with mixed results. We hypothesized that targeting limbic neural pathways would modulate the affective sphere of pain and alleviate suffering. We conducted a prospective, double-blinded, randomized, placebo-controlled, crossover study of DBS targeting the ventral striatum/anterior limb of the internal capsule (VS/ALIC) in 10 patients with poststroke pain syndrome. One month after bilateral DBS, patients were randomized to active DBS or sham for 3 months, followed by crossover for another 3-month period. The primary endpoint was a ≥50% improvement on the Pain Disability Index in 50% of patients with active DBS compared to sham. This 6-month blinded phase was followed by an 18-month open stimulation phase. Nine participants completed randomization. Although this trial was negative for its primary and secondary endpoints, we did observe significant differences in multiple outcome measures related to the affective sphere of pain (eg, Montgomery-Åsberg Depression Rating Scale, Beck Depression Inventory, Affective Pain Rating Index of the Short-Form McGill Pain Questionnaire). Fourteen serious adverse events were recorded and resolved. VS/ALIC DBS to modulate the affective sphere of pain represents a paradigm shift in chronic pain management. Although this exploratory study was negative for its primary endpoint, VS/ALIC DBS demonstrated an acceptable safety profile and statistically significant improvements on multiple outcome measures related to the affective sphere of pain. Therefore, we believe these results justify further work on neuromodulation therapies targeting the affective sphere of pain. Ann Neurol 2017;81:653-663. © 2017 American Neurological Association.

  5. Nudging guideline-concordant antibiotic prescribing: a randomized clinical trial.

    PubMed

    Meeker, Daniella; Knight, Tara K; Friedberg, Mark W; Linder, Jeffrey A; Goldstein, Noah J; Fox, Craig R; Rothfeld, Alan; Diaz, Guillermo; Doctor, Jason N

    2014-03-01

    "Nudges" that influence decision making through subtle cognitive mechanisms have been shown to be highly effective in a wide range of applications, but there have been few experiments to improve clinical practice. To investigate the use of a behavioral "nudge" based on the principle of public commitment in encouraging the judicious use of antibiotics for acute respiratory infections (ARIs). Randomized clinical trial in 5 outpatient primary care clinics. A total of 954 adults had ARI visits during the study timeframe: 449 patients were treated by clinicians randomized to the posted commitment letter (335 in the baseline period, 114 in the intervention period); 505 patients were treated by clinicians randomized to standard practice control (384 baseline, 121 intervention). The intervention consisted of displaying poster-sized commitment letters in examination rooms for 12 weeks. These letters, featuring clinician photographs and signatures, stated their commitment to avoid inappropriate antibiotic prescribing for ARIs. Antibiotic prescribing rates for antibiotic-inappropriate ARI diagnoses in baseline and intervention periods, adjusted for patient age, sex, and insurance status. Baseline rates were 43.5% and 42.8% for control and poster, respectively. During the intervention period, inappropriate prescribing rates increased to 52.7% for controls but decreased to 33.7% in the posted commitment letter condition. Controlling for baseline prescribing rates, we found that the posted commitment letter resulted in a 19.7 absolute percentage reduction in inappropriate antibiotic prescribing rate relative to control (P = .02). There was no evidence of diagnostic coding shift, and rates of appropriate antibiotic prescriptions did not diminish over time. Displaying poster-sized commitment letters in examination rooms decreased inappropriate antibiotic prescribing for ARIs. The effect of this simple, low-cost intervention is comparable in magnitude to costlier, more

  6. Exergaming and older adult cognition: a cluster randomized clinical trial.

    PubMed

    Anderson-Hanley, Cay; Arciero, Paul J; Brickman, Adam M; Nimon, Joseph P; Okuma, Naoko; Westen, Sarah C; Merz, Molly E; Pence, Brandt D; Woods, Jeffrey A; Kramer, Arthur F; Zimmerman, Earl A

    2012-02-01

    Dementia cases may reach 100 million by 2050. Interventions are sought to curb or prevent cognitive decline. Exercise yields cognitive benefits, but few older adults exercise. Virtual reality-enhanced exercise or "exergames" may elicit greater participation. To test the following hypotheses: (1) stationary cycling with virtual reality tours ("cybercycle") will enhance executive function and clinical status more than traditional exercise; (2) exercise effort will explain improvement; and (3) brain-derived neurotrophic growth factor (BDNF) will increase. Multi-site cluster randomized clinical trial (RCT) of the impact of 3 months of cybercycling versus traditional exercise, on cognitive function in older adults. Data were collected in 2008-2010; analyses were conducted in 2010-2011. 102 older adults from eight retirement communities enrolled; 79 were randomized and 63 completed. A recumbent stationary ergometer was utilized; virtual reality tours and competitors were enabled on the cybercycle. Executive function (Color Trails Difference, Stroop C, Digits Backward); clinical status (mild cognitive impairment; MCI); exercise effort/fitness; and plasma BDNF. Intent-to-treat analyses, controlling for age, education, and cluster randomization, revealed a significant group X time interaction for composite executive function (p=0.002). Cybercycling yielded a medium effect over traditional exercise (d=0.50). Cybercyclists had a 23% relative risk reduction in clinical progression to MCI. Exercise effort and fitness were comparable, suggesting another underlying mechanism. A significant group X time interaction for BDNF (p=0.05) indicated enhanced neuroplasticity among cybercyclists. Cybercycling older adults achieved better cognitive function than traditional exercisers, for the same effort, suggesting that simultaneous cognitive and physical exercise has greater potential for preventing cognitive decline. This study is registered at Clinicaltrials.gov NCT01167400. Copyright

  7. Surgical trial in traumatic intracerebral hemorrhage (STITCH(Trauma)): study protocol for a randomized controlled trial

    PubMed Central

    2012-01-01

    Background Intracranial hemorrhage occurs in over 60% of severe head injuries in one of three types: extradural (EDH); subdural (SDH); and intraparenchymal (TICH). Prompt surgical removal of significant SDH and EDH is established and widely accepted. However, TICH is more common and is found in more than 40% of severe head injuries. It is associated with a worse outcome but the role for surgical removal remains undefined. Surgical practice in the treatment of TICHs differs widely around the world. The aim of early surgery in TICH removal is to prevent secondary brain injury. There have been trials of surgery for spontaneous ICH (including the STICH II trial), but none so far of surgery for TICH. Methods/Design The UK National Institutes of Health Research has funded STITCH(Trauma) to determine whether a policy of early surgery in patients with TICH improves outcome compared to a policy of initial conservative treatment. It will include a health economics component and carry out a subgroup analysis of patients undergoing invasive monitoring. This is an international multicenter pragmatic randomized controlled trial. Patients are eligible if: they are within 48 h of injury; they have evidence of TICH on CT scan with a confluent volume of attenuation significantly raised above that of the background white and grey matter that has a total volume >10 mL; and their treating neurosurgeon is in equipoise. Patients will be ineligible if they have: a significant surface hematoma (EDH or SDH) requiring surgery; a hemorrhage/contusion located in the cerebellum; three or more separate hematomas fulfilling inclusion criteria; or severe pre-existing physical or mental disability or severe co-morbidity which would lead to poor outcome even if the patient made a full recovery from the head injury. Patients will be randomized via an independent service. Patients randomized to surgery receive surgery within 12 h. Both groups will be monitored according to standard neurosurgical

  8. Protocol for the Locomotor Experience Applied Post-stroke (LEAPS) trial: a randomized controlled trial

    PubMed Central

    Duncan, Pamela W; Sullivan, Katherine J; Behrman, Andrea L; Azen, Stanley P; Wu, Samuel S; Nadeau, Stephen E; Dobkin, Bruce H; Rose, Dorian K; Tilson, Julie K

    2007-01-01

    Background Locomotor training using body weight support and a treadmill as a therapeutic modality for rehabilitation of walking post-stroke is being rapidly adopted into clinical practice. There is an urgent need for a well-designed trial to determine the effectiveness of this intervention. The objective of the Locomotor Experience Applied Post-Stroke (LEAPS) trial is to determine if there is a difference in the proportion of participants who recover walking ability at one year post-stroke when randomized to a specialized locomotor training program (LTP), conducted at 2- or 6-months post-stroke, or those randomized to a home based non-specific, low intensity exercise intervention (HEP) provided 2 months post-stroke. We will determine if the timing of LTP delivery affects gait speed at 1 year and whether initial impairment severity interacts with the timing of LTP. The effect of number of treatment sessions will be determined by changes in gait speed taken pre-treatment and post-12, -24, and -36 sessions. Methods/Design We will recruit 400 adults with moderate or severe walking limitations within 30 days of stroke onset. At two months post stroke, participants are stratified by locomotor impairment severity as determined by overground walking speed and randomly assigned to one of three groups: (a) LTP-Early; (b) LTP-Late or (c) Home Exercise Program -Early. The LTP program includes body weight support on a treadmill and overground training. The LTP and HEP interventions are delivered for 36 sessions over 12 weeks. Primary outcome measure include successful walking recovery defined as the achievement of a 0.4 m/s gait speed or greater by persons with initial severe gait impairment or the achievement of a 0.8 m/s gait speed or greater by persons with initial moderate gait impairment. LEAPS is powered to detect a 20% difference in the proportion of participants achieving successful locomotor recovery between the LTP groups and the HEP group, and a 0.1 m/s mean

  9. Ghana randomized air pollution and health study (GRAPHS): study protocol for a randomized controlled trial.

    PubMed

    Jack, Darby W; Asante, Kwaku Poku; Wylie, Blair J; Chillrud, Steve N; Whyatt, Robin M; Ae-Ngibise, Kenneth A; Quinn, Ashlinn K; Yawson, Abena Konadu; Boamah, Ellen Abrafi; Agyei, Oscar; Mujtaba, Mohammed; Kaali, Seyram; Kinney, Patrick; Owusu-Agyei, Seth

    2015-09-22

    Household air pollution exposure is a major health risk, but validated interventions remain elusive. The Ghana Randomized Air Pollution and Health Study (GRAPHS) is a cluster-randomized trial that evaluates the efficacy of clean fuels (liquefied petroleum gas, or LPG) and efficient biomass cookstoves in the Brong-Ahafo region of central Ghana. We recruit pregnant women into LPG, efficient cookstove, and control arms and track birth weight and physician-assessed severe pneumonia incidence in the first year of life. A woman is eligible to participate if she is in the first or second trimester of pregnancy and carrying a live singleton fetus, if she is the primary cook, and if she does not smoke. We hypothesize that babies born to intervention mothers will weigh more and will have fewer cases of physician-assessed severe pneumonia in the first year of life. Additionally, an extensive personal air pollution exposure monitoring effort opens the way for exposure-response analyses, which we will present alongside intention-to-treat analyses. Major funding was provided by the National Institute of Environmental Health Sciences, The Thrasher Research Fund, and the Global Alliance for Clean Cookstoves. Household air pollution exposure is a major health risk that requires well-tested interventions. GRAPHS will provide important new evidence on the efficacy of both efficient biomass cookstoves and LPG, and will thus help inform health and energy policies in developing countries. The trial was registered with clinicaltrials.gov on 13 April 2011 with the identifier NCT01335490 .

  10. A meta-analysis of randomized controlled trials of telmisartan for flow-mediated dilatation.

    PubMed

    Takagi, Hisato; Umemoto, Takuya

    2014-09-01

    There have been a number of small-sized underpowered randomized controlled trials to assess effects of telmisartan on flow-mediated dilatation (FMD). To determine whether telmisartan increases FMD, we performed a meta-analysis of these trials. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched through December 2013. Eligible studies were prospective randomized controlled trials of telmisartan reporting FMD as an outcome. Search terms included: telmisartan; endothelial function/dysfunction; flow-mediated dilation/dilatation/vasodilation/vasodilatation; and randomized, randomly or randomization. Included studies were reviewed to determine the number of patients randomized, mean duration of treatment and percent changes of FMD. Of 25 potentially relevant articles screened initially, seven reports of randomized trials enrolling a total of 398 patients were identified and included. A pooled analysis of the seven trials demonstrated a statistically significant increase in FMD by 48.7%, with telmisartan relative to control in the random-effects model (mean difference, 48.72%; 95% confidence interval, 15.37-82.08%; P for effect=0.004; P for heterogeneity <0.00001). Exclusion of any single trial from the analysis did not substantively alter the overall result of our analysis. There was no evidence of significant publication bias. In conclusion, the present meta-analysis of seven randomized controlled trials enrolling a total of 398 patients confirmed the evidence of a significant increase in FMD with telmisartan, which suggests that telmisartan may improve endothelial dysfunction.

  11. A randomized trial comparing concise and standard consent forms in the START trial.

    PubMed

    Grady, Christine; Touloumi, Giota; Walker, A Sarah; Smolskis, Mary; Sharma, Shweta; Babiker, Abdel G; Pantazis, Nikos; Tavel, Jorge; Florence, Eric; Sanchez, Adriana; Hudson, Fleur; Papadopoulos, Antonios; Emanuel, Ezekiel; Clewett, Megan; Munroe, David; Denning, Eileen

    2017-01-01

    Improving the effectiveness and efficiency of research informed consent is a high priority. Some express concern about longer, more complex, written consent forms creating barriers to participant understanding. A recent meta-analysis concluded that randomized comparisons were needed. We conducted a cluster-randomized non-inferiority comparison of a standard versus concise consent form within a multinational trial studying the timing of starting antiretroviral therapy in HIV+ adults (START). Interested sites were randomized to standard or concise consent forms for all individuals signing START consent. Participants completed a survey measuring comprehension of study information and satisfaction with the consent process. Site personnel reported usual site consent practices. The primary outcome was comprehension of the purpose of randomization (pre-specified 7.5% non-inferiority margin). 77 sites (2429 participants) were randomly allocated to use standard consent and 77 sites (2000 participants) concise consent, for an evaluable cohort of 4229. Site and participant characteristics were similar for the two groups. The concise consent was non-inferior to the standard consent on comprehension of randomization (80.2% versus 82%, site adjusted difference: 0.75% (95% CI -3.8%, +5.2%)); and the two groups did not differ significantly on total comprehension score, satisfaction, or voluntariness (p>0.1). Certain independent factors, such as education, influenced comprehension and satisfaction but not differences between consent groups. An easier to read, more concise consent form neither hindered nor improved comprehension of study information nor satisfaction with the consent process among a large number of participants. This supports continued efforts to make consent forms more efficient. Informed consent substudy was registered as part of START study in clinicaltrials.gov #NCT00867048, and EudraCT # 2008-006439-12.

  12. Secnidazole Treatment of Bacterial Vaginosis: A Randomized Controlled Trial.

    PubMed

    Hillier, Sharon L; Nyirjesy, Paul; Waldbaum, Arthur S; Schwebke, Jane R; Morgan, Franklin G; Adetoro, Nikki A; Braun, Carol J

    2017-08-01

    To evaluate secnidazole as a single oral dose treatment for bacterial vaginosis in a phase 2 randomized, double-blind, placebo-controlled study. In a phase 2, randomized, double-blind, dose-ranging, placebo-controlled study, women with bacterial vaginosis who met all Amsel criteria (discharge; pH 4.7 or greater; 20% or greater clue cells; positive whiff test) were randomized one to one to one at 24 U.S. centers to 1 or 2 g secnidazole compared with placebo. The primary endpoint was clinical cure (normalization of discharge, amine odor, and clue cells) 21-30 days after treatment. Secondary endpoints included microbiologic cure, defined as a Nugent score of 0-3, and therapeutic cure, defined as meeting criteria for both clinical and microbiologic cure. The modified intent to treat was used for efficacy analyses and included all randomized patients who met the enrollment criteria. Assuming a clinical cure rate of 40% in the active groups and 15% in the placebo group, a sample size of 52 patients per group provided approximately 80% power to detect a significant difference between groups (.05 level [two-sided]) using a Cochran-Mantel-Haenszel test. Between May and September 2014, 215 patients were enrolled. In the intent-to-treat population, the clinical cure rate was 65.3% for the 2-g group, 49.3% for the 1-g group, and 19.4% for the placebo group. The modified intent-to-treat population included 188 women (median age 33 years; 32% with four or more bacterial vaginosis episodes in the previous year; 54% black) with baseline Nugent scores 4 or greater. Clinical, microbiologic, and therapeutic cure rates were 67.7%, 40.3%, and 40.3% for 2 g secnidazole and 51.6%, 23.4%, and 21.9% for 1 g secnidazole compared with 17.7%, 6.5%, and 6.5% for placebo, respectively (P<.05 for secnidazole compared with placebo; all endpoints). Both doses were well-tolerated. Oral granules containing 1 and 2 g secnidazole were superior to placebo in bacterial vaginosis treatment (P<.001 for

  13. Aerobic exercise for Alzheimer's disease: A randomized controlled pilot trial.

    PubMed

    Morris, Jill K; Vidoni, Eric D; Johnson, David K; Van Sciver, Angela; Mahnken, Jonathan D; Honea, Robyn A; Wilkins, Heather M; Brooks, William M; Billinger, Sandra A; Swerdlow, Russell H; Burns, Jeffrey M

    2017-01-01

    There is increasing interest in the role of physical exercise as a therapeutic strategy for individuals with Alzheimer's disease (AD). We assessed the effect of 26 weeks (6 months) of a supervised aerobic exercise program on memory, executive function, functional ability and depression in early AD. This study was a 26-week randomized controlled trial comparing the effects of 150 minutes per week of aerobic exercise vs. non-aerobic stretching and toning control intervention in individuals with early AD. A total of 76 well-characterized older adults with probable AD (mean age 72.9 [7.7]) were enrolled and 68 participants completed the study. Exercise was conducted with supervision and monitoring by trained exercise specialists. Neuropsychological tests and surveys were conducted at baseline,13, and 26 weeks to assess memory and executive function composite scores, functional ability (Disability Assessment for Dementia), and depressive symptoms (Cornell Scale for Depression in Dementia). Cardiorespiratory fitness testing and brain MRI was performed at baseline and 26 weeks. Aerobic exercise was associated with a modest gain in functional ability (Disability Assessment for Dementia) compared to individuals in the ST group (X2 = 8.2, p = 0.02). There was no clear effect of intervention on other primary outcome measures of Memory, Executive Function, or depressive symptoms. However, secondary analyses revealed that change in cardiorespiratory fitness was positively correlated with change in memory performance and bilateral hippocampal volume. Aerobic exercise in early AD is associated with benefits in functional ability. Exercise-related gains in cardiorespiratory fitness were associated with improved memory performance and reduced hippocampal atrophy, suggesting cardiorespiratory fitness gains may be important in driving brain benefits. ClinicalTrials.gov NCT01128361.

  14. Randomized trial of neoadjuvant chemotherapy in oropharyngeal carcinoma

    PubMed Central

    Domenge, C; Hill, C; Lefebvre, J L; De Raucourt, D; Rhein, B; Wibault, P; Marandas, P; Coche-Dequeant, B; Stromboni-Luboinski, M; Sancho-Garnier, H; Luboinski, B

    2000-01-01

    The objective of the study was to evaluate the effect of neoadjuvant chemotherapy on the survival of patients with oropharyngeal cancer. Patients with a squamous cell carcinoma of the oropharynx for whom curative radiotherapy or surgery was considered feasible were entered in a multicentric randomized trial comparing neoadjuvant chemotherapy followed by loco-regional treatment to the same loco-regional treatment without chemotherapy. The loco-regional treatment consisted either of surgery plus radiotherapy or of radiotherapy alone. Three cycles of chemotherapy consisting of Cisplatin (100 mg/m2) on day 1 followed by a 24-hour i.v. infusion of fluorouracil (1000 mg/m2/day) for 5 days were delivered every 21 days. 2–3 weeks after the end of chemotherapy, local treatment was performed. The trial was conducted by the Groupe d'Etude des Tumeurs de la Tête Et du Cou (GETTEC). A total of 318 patients were enrolled in the study between 1986 and 1992. Overall survival was significantly better (P = 0.03) in the neoadjuvant chemotherapy group than in the control group, with a median survival of 5.1 years versus 3.3 years in the no chemotherapy group. The effect of neoadjuvant chemotherapy on event-free survival was smaller and of borderline significance (P = 0.11). Stratification of the results on the type of local treatment, surgery plus radiotherapy or radiotherapy alone, did not reveal any heterogeneity in the effect of chemotherapy. © 2000 Cancer Research Campaign http://www.bjcancer.com PMID:11189100

  15. Clarithromycin in GABA-related Hypersomnolence: A Randomized, Crossover Trial

    PubMed Central

    Trotti, Lynn Marie; Saini, Prabhjyot; Bliwise, Donald L.; Freeman, Amanda A.; Jenkins, Andrew; Rye, David B.

    2016-01-01

    Objective Some central hypersomnolence syndromes are associated with a positive allosteric modulator of GABA-A receptors in cerebrospinal fluid. Negative allosteric modulators of GABA-A receptors, including clarithromycin, have been reported to reduce sleepiness in these patients. We sought to systematically assess the effects of clarithromycin on objective vigilance and subjective sleepiness. Methods This was a five-week, randomized, placebo-controlled, double-blind, crossover trial of clarithromycin 500 mg with breakfast and lunch, in patients with hypersomnolence syndromes (excluding narcolepsy with cataplexy) and evidence for abnormal cerebrospinal fluid potentiation of GABA-A receptors. The study occurred at a university-affiliated medical center. The primary outcome measure was median reaction time on the psychomotor vigilance task (PVT) at week 2 in each condition. Secondary outcomes included the Epworth Sleepiness Scale, Stanford Sleepiness Scale, Functional Outcomes of Sleep, Pittsburgh Sleep Quality Index, the SF-36, and additional PVT measures. Results Twenty-three patients began treatment. Three patients dropped out, and final analyses were performed on twenty complete cases. Median reaction time was not significantly different between clarithromycin and placebo. Subjective measures of sleepiness were significantly improved on clarithromycin versus placebo. Altered taste perception occurred, but was the only side effect more common on clarithromycin than placebo. No serious adverse events occurred. Interpretation Subjective sleepiness, but not psychomotor vigilance, improved during a two-week course of clarithromycin. Although additional studies are needed, this suggests that clarithromycin may be a reasonable treatment option in patients with treatment-refractory hypersomnolence. This trial was registered at clinicaltrials.gov (NCT01146600) and supported by the American Sleep Medicine Foundation. PMID:26094838

  16. Cardiopulmonary resuscitation support application on a smartphone - randomized controlled trial.

    PubMed

    Sakai, Tomohiko; Kitamura, Tetsuhisa; Nishiyama, Chika; Murakami, Yukiko; Ando, Masahiko; Kawamura, Takashi; Tasaki, Osamu; Kuwagata, Yasuyuki; Shimazu, Takeshi; Iwami, Taku

    2015-01-01

    This simulation trial aimed to compare the quality of cardiopulmonary resuscitation (CPR) with and without the newly-developed CPR support application on smartphones. In this trial, participants were randomly assigned to either the CPR support application group or the control group, stratified by sex and previous CPR training. Participants' CPR skills were evaluated by a 2-min case-based scenario test using the Leardal Resusci Anne PC Skill reporting Manikin System(®). The outcome measures were the proportion of chest compressions performed in each group and the number of total chest compressions and appropriate chest compressions performed during the 2-min test period. A total of 84 participants were enrolled and completed the protocol. All participants in the CPR support application group performed chest compressions, compared with only 31 (75.6%) in the control group (P<0.001). Among participants who performed chest compressions during the 2-min test period, the number of total chest compressions was significantly higher in the CPR support application group than in the control group (211.6±29.5 vs. 77.0±43.3, P<0.001). The number of appropriate chest compressions tended to be greater in the CPR support application group than in the control group, although it was statistically insignificant (30.3±57.3 vs. 17.2±28.7, P=0.246). In this cohort of laypersons, the newly-developed CPR support application for smartphones contributed to increasing the implementation rate and the number of total chest compressions performed and may assist in improving the survival rate for out-of-hospital cardiac arrests (UMIN000004740).

  17. Personal health records and hypertension control: a randomized trial.

    PubMed

    Wagner, Peggy J; Dias, James; Howard, Shalon; Kintziger, Kristina W; Hudson, Matthew F; Seol, Yoon-Ho; Sodomka, Pat

    2012-01-01

    To examine the impact of a personal health record (PHR) in patients with hypertension measured by changes in biological outcomes, patient empowerment, patient perception of quality of care, and use of medical services. A cluster-randomized effectiveness trial with PHR and no PHR groups was conducted in two ambulatory clinics. 453 of 1686 (26.4%) patients approached were included in the analyses. A PHR tethered to the patient's electronic medical record (EMR) was the primary intervention and included security measures, patient control of access, limited transmission of EMR data, blood pressure (BP) tracking, and appointment assistance. BP was the main outcome measure. Patient empowerment was assessed using the Patient Activation Measure and Patient Empowerment Scale. Quality of care was assessed using the Clinician and Group Assessment Score (CAHPS) and the Patient Assessment of Chronic Illness Care. Frequency of use of medical services was self-reported. No impact of the PHR was observed on BP, patient activation, patient perceived quality, or medical utilization in the intention-to-treat analysis. Sub-analysis of intervention patients self-identified as active PHR users (25.7% of those with available information) showed a 5.25-point reduction in diastolic BP. Younger age, self-reported computer skills, and more positive provider communication ratings were associated with frequency of PHR use. Few patients provided with a PHR actually used the PHR with any frequency. Thus simply providing a PHR may have limited impact on patient BP, empowerment, satisfaction with care, or use of health services without additional education or clinical intervention designed to increase PHR use. http://ClinicalTrials.gov Identifier: NCT01317537.

  18. Prosthetic heart valves: Objective Performance Criteria versus randomized clinical trial.

    PubMed

    Grunkemeier, Gary L; Jin, Ruyun; Starr, Albert

    2006-09-01

    The current Food and Drug Administration (FDA) heart valve guidance document uses an objective performance criteria (OPC) methodology to evaluate the clinical performance of prosthetic heart valves. OPC are essentially historical controls, but they have turned out to be an adequate, and perhaps optimal, study design in this situation. Heart valves have a simple open-and-close mechanism, device effectiveness is easy to document, and the common complications (thromboembolism, thrombosis, bleeding, leak, and infection) are well known and easily detected. Thus, randomized clinical trials (RCTs) have not been deemed necessary for the regulatory approval of prosthetic heart valves. The OPC are derived from the average complication rates of all approved heart valves. Studies based on OPC have been shown to work well; many different valve models have gained FDA market approval based on this methodology. Although heart valve RCTs are not required by the FDA, they have been done to compare valves or treatment regimens after approval. Recently, the Artificial Valve Endocarditis Reduction Trial (AVERT) was designed to compare a new Silzone sewing ring, designed to reduce infection, with the Standard sewing ring on a St. Jude Medical heart valve. This was the largest heart valve RCT ever proposed (4,400 valve patients, followed for as long as 4 years), but it was stopped prematurely because of a high leak rate associated with the Silzone valve. Examining the results showed that a much smaller, OPC-based study with 800 patient-years would have been sufficient to disclose this complication of the Silzone valve.

  19. A randomized trial of immunotherapy for persistent genital warts

    PubMed Central

    Jardine, David; Lu, Jieqiang; Pang, James; Palmer, Cheryn; Tu, Quanmei; Chuah, John; Frazer, Ian H.

    2012-01-01

    Aim To determine whether immunotherapy with HPV6 L1 virus like particles (VLPs) without adjuvant (VLP immunotherapy) reduces recurrence of genital warts following destructive therapy. Trial design A randomized placebo controlled blinded study of treatment of recurrent genital warts amenable to destructive therapy, conducted independently in Australia and China. Methods Patients received conventional destructive therapy of all evident warts together with intramuscular administration of 1, 5 or 25 µg of VLP immunotherapy, or of placebo immunotherapy (0.9% NaCl), as immunotherapy at week 0 and week 4. Primary outcome, assessed at week 8, was recurrence of visible warts. Results Of 33 protocol compliant Brisbane recipients of placebo immunotherapy, 11 were disease free at two months, and a further 9 demonstrated reduction of > 50% in total wart area. Wart area reduction following destructive treatment correlated with prior duration of disease. Among 102 protocol compliant Brisbane recipients of VLP immunotherapy, disease reduction was significantly greater than among the placebo immunotherapy (50% ± s.e.m. 7%) recipients for subjects receiving 5 µg or 25 µg of VLP immunotherapy/dose (71% ± s.e.m.7%) but not for those receiving 1 µg VLP immunotherapy/dose (42% ± 7%). Of 52 protocol compliant placebo immunotherapy recipients in Wenzhou, 37 were disease free at two months, and a further 8 had > 50% disease reduction. Prior disease duration was much shorter in Wenzhou subject (8.1 ± 1.1 mo) than in Brisbane subjects (53.7 ± 5.5 mo). No significant reduction in mean wart area was observed for the 168 Wenzhou protocol compliant subjects who also received VLP immunotherapy. Conclusions This study confirms the findings in a previous open label trial that administration of VLP immunotherapy may assist in clearance of recurrent genital warts in patients for whom destructive therapy is unsuccessful and that unsuccessful destructive therapy is more common with increasing

  20. A Randomized Trial of Prenatal versus Postnatal Repair of Myelomeningocele

    PubMed Central

    Adzick, N. Scott; Thom, Elizabeth A.; Spong, Catherine Y.; Brock, John W.; Burrows, Pamela K.; Johnson, Mark P.; Howell, Lori J.; Farrell, Jody A.; Dabrowiak, Mary E.; Sutton, Leslie N.; Gupta, Nalin; Tulipan, Noel B.; D'Alton, Mary E.; Farmer, Diana L.

    2013-01-01

    Background Prenatal repair of myelomeningocele, the most common form of spina bifida, may result in better neurologic function than repair deferred until after delivery. We compared outcomes of in utero repair with standard postnatal repair. Methods We randomly assigned eligible women to undergo either prenatal surgery before 26 weeks of gestation or standard postnatal repair. One primary outcome was a composite of fetal or neonatal death or the need for placement of a cerebrospinal fluid shunt by the age of 12 months. Another primary outcome at 30 months was a composite of mental development and motor function. Results The trial was stopped for efficacy of prenatal surgery after the recruitment of 183 of a planned 200 patients. This report is based on results in 158 patients whose children were evaluated at 12 months. The first primary outcome occurred in 68% of the infants in the prenatal-surgery group and in 98% of those in the postnatal-surgery group (relative risk, 0.70; 97.7% confidence interval [CI], 0.58 to 0.84; P<0.001). Actual rates of shunt placement were 40% in the prenatal-surgery group and 82% in the postnatal-surgery group (relative risk, 0.48; 97.7% CI, 0.36 to 0.64; P<0.001). Prenatal surgery also resulted in improvement in the composite score for mental development and motor function at 30 months (P = 0.007) and in improvement in several secondary outcomes, including hindbrain herniation by 12 months and ambulation by 30 months. However, prenatal surgery was associated with an increased risk of preterm delivery and uterine dehiscence at delivery. Conclusions Prenatal surgery for myelomeningocele reduced the need for shunting and improved motor outcomes at 30 months but was associated with maternal and fetal risks. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00060606.) PMID:21306277

  1. Mortality in the randomized, controlled lung intergroup trial of isotretinoin.

    PubMed

    Lee, J Jack; Feng, Lei; Reshef, Daniel S; Sabichi, Anita L; Williams, Brendell; Rinsurongkawong, Waree; Wistuba, Ignacio I; Lotan, Reuben; Lippman, Scott M

    2010-06-01

    In 2001, we reported that mortality may have been higher with isotretinoin (30 mg/d for 3 years) than with placebo in the subgroup of current smokers among the 1,166 patients with definitively resected early-stage non-small cell lung cancer who participated in the randomized, controlled Lung Intergroup Trial. We report the overall and cause (cancer, cardiovascular disease, or other)-specific mortality associated with long-term isotretinoin after an extended median follow-up of 6.2 years that included the capture of cause-of-death data from 428 deceased patients. Overall mortality was 36.7% in each of the two trial arms, about two thirds related to cancer and one third to other or unknown causes. Overall and cancer deaths increased in current smokers in the isotretinoin arm during the treatment and the extended follow-up period. No mortality end point increased among never smokers and former smokers taking isotretinoin, and cancer deaths decreased marginally in this combined subgroup. Isotretinoin also increased deaths from cardiovascular disease in current smokers. The present analysis supports the safety of protracted isotretinoin use in the combined group of never smokers and former smokers, which has important public health implications, for example, for treating acne in young people. The increased mortality in current smokers in this study is further evidence of the multifaceted danger of active smoking. The overall indications of this study have public health implications for treating acne in young people and other uses of retinoids in smokers.

  2. Randomized trial of behavior therapy for adults with Tourette syndrome.

    PubMed

    Wilhelm, Sabine; Peterson, Alan L; Piacentini, John; Woods, Douglas W; Deckersbach, Thilo; Sukhodolsky, Denis G; Chang, Susanna; Liu, Haibei; Dziura, James; Walkup, John T; Scahill, Lawrence

    2012-08-01

    Tics in Tourette syndrome begin in childhood, peak in early adolescence, and often decrease by early adulthood. However, some adult patients continue to have impairing tics. Medications for tics are often effective but can cause adverse effects. Behavior therapy may offer an alternative but has not been examined in a large-scale controlled trial in adults. To test the efficacy of a comprehensive behavioral intervention for tics in adults with Tourette syndrome of at least moderate severity. A randomized controlled trial with posttreatment evaluations at 3 and 6 months for positive responders. Three outpatient research clinics. Patients (N = 122; 78 males; age range, 16-69 years) with Tourette syndrome or chronic tic disorder were recruited between December 27, 2005, and May 21, 2009. Patients received 8 sessions of comprehensive behavioral intervention for tics or 8 sessions of supportive treatment for 10 weeks. Patients with a positive response were given 3 monthly booster sessions. Total tic score on the Yale Global Tic Severity Scale and the Clinical Global Impression-Improvement scale rated by a clinician masked to treatment assignment. Behavior therapy was associated with a significantly greater mean (SD) decrease on the Yale Global Tic Severity Scale (24.0 [6.47] to 17.8 [7.32]) from baseline to end point compared with the control treatment (21.8 [6.59] to 19.3 [7.40]) (P < .001; effect size = 0.57). Twenty-four of 63 patients (38.1%) were rated as much improved or very much improved on the Clinical Global Impression-Improvement scale compared with 4 of 63 (6.4%) in the control group (P < .001). Attrition was 13.9%, with no difference across groups. Patients receiving behavior therapy who were available for assessment at 6 months after treatment showed continued benefit. Comprehensive behavior therapy is a safe and effective intervention for adults with Tourette syndrome. clinicaltrials.gov Identifier: NCT00231985.

  3. Vasopressin Boosts Placebo Analgesic Effects in Women: A Randomized Trial

    PubMed Central

    Colloca, Luana; Pine, Daniel S.; Ernst, Monique; Miller, Franklin G.; Grillon, Christian

    2015-01-01

    Background Social cues and interpersonal interactions strongly contribute to evoke placebo effects that are pervasive in medicine and depend upon the activation of endogenous modulatory systems. Here we explore the possibility to boost placebo effects by targeting pharmacologically the vasopressin system, characterized by a sexually dimorphic response and involved in the regulation of human and nonhuman social behaviors. Methods We enrolled 109 healthy participants and studied the effects of intranasal administration of Avp1a and Avp1b arginine vasopressin receptor agonists against 1) no-treatment, 2) oxytocin, and 3) saline, in a randomized, placebo-controlled, double-blind, parallel design trial using a well-established model of placebo analgesia while controlling for sex differences. Results Vasopressin agonists boosted placebo effects in women but had no effect in men. The effects of vasopressin on expectancy-induced analgesia were significantly larger than those observed in the no-treatment (p<004), oxytocin (p<0.001) and saline (p<0.015) groups. Moreover, women with lower dispositional anxiety and cortisol levels showed the largest vasopressin-induced modulation of placebo effects, suggesting a moderating interplay between pre-existing psychological factors and cortisol changes. Conclusions This is the first study that demonstrates that arginine vasopressin boosts placebo effects and that the effect of vasopressin depends upon a significant sex by treatment interaction. These findings are novel and might open up new avenues for clinically relevant research due to the therapeutic potentials of vasopressin and oxytocin as well as the possibility to systematically control for influences of placebo responses in clinical trials. PMID:26321018

  4. AIDS Clinical Trials Group Longitudinal Linked Randomized Trials (ALLRT): Rationale, Design, and Baseline Characteristics

    PubMed Central

    Smurzynski, Marlene; Collier, Ann C.; Koletar, Susan L.; Bosch, Ronald J.; Wu, Kunling; Bastow, Barbara; Benson, Constance A.

    2009-01-01

    Purpose ALLRT is a longitudinal cohort study of HIV-infected subjects prospectively randomized into selected clinical trials for antiretroviral (ARV) treatment-naïve and ARV treatment-experienced individuals conducted by the AIDS Clinical Trials Group (ACTG). We describe the rationale, design, and baseline characteristics of the ALLRT cohort and its potential to address important research questions related to ARV therapy. Method Standardized visits occur every 16 weeks to evaluate long-term clinical, virologic, and immunologic outcomes associated with ARV treatment. Results A total of 4,371 subjects enrolled in ALLRT from January 2000 through June 2007. Of these, 3,146 (72%) were ARV naïve at parent study entry (18% female, 44% white, 32% black, 21% Hispanic; median age 37 years, CD4 count 218 cells/μL, follow-up 3.6 years; 343 [11%] followed ≥8 years) and 1,225 (28%) were treatment experienced (13% female, 59% white, 20% black, 17% Hispanic; median age 42 years, CD4 count 325 cells/μL, follow-up 5.7 years). Conclusions ALLRT provides the opportunity to understand long-term ramifications of therapeutic ARV choices and determine whether these vary by treatment regimen, timing of treatment initiation, or treatment changes over long-term follow-up. Investigations based on uniform data and specimen collection in the context of randomized ARV treatments will be critical to developing more successful long-term therapeutic strategies for HIV treatment. PMID:18753121

  5. A Randomized Trial Comparing Skin Antiseptic Agents at Cesarean Delivery

    PubMed Central

    Tuuli, Methodius G.; Liu, Jingxia; Stout, Molly J.; Martin, Shannon; Cahill, Alison G.; Odibo, Anthony O.; Colditz, Graham A.; Macones, George A.

    2016-01-01

    BACKGROUND Preoperative skin antisepsis has the potential to decrease the risk of surgical-site infection. However, evidence is limited to guide the choice of antiseptic agent at cesarean delivery, which is the most common major surgical procedure among women in the United States. METHODS In this single-center, randomized, controlled trial, we evaluated whether the use of chlorhexidine–alcohol for preoperative skin antisepsis was superior to the use of iodine–alcohol for the prevention of surgical-site infection after cesarean delivery. We randomly assigned patients undergoing cesarean delivery to skin preparation with either chlorhexidine–alcohol or iodine–alcohol. The primary outcome was superficial or deep surgical-site infection within 30 days after cesarean delivery, on the basis of definitions from the Centers for Disease Control and Prevention. RESULTS From September 2011 through June 2015, a total of 1147 patients were enrolled; 572 patients were assigned to chlorhexidine–alcohol and 575 to iodine–alcohol. In an intention-to-treat analysis, surgical-site infection was diagnosed in 23 patients (4.0%) in the chlorhexidine–alcohol group and in 42 (7.3%) in the iodine–alcohol group (relative risk, 0.55; 95% confidence interval, 0.34 to 0.90; P = 0.02). The rate of superficial surgical-site infection was 3.0% in the chlorhexidine–alcohol group and 4.9% in the iodine–alcohol group (P = 0.10); the rate of deep infection was 1.0% and 2.4%, respectively (P = 0.07). The frequency of adverse skin reactions was similar in the two groups. CONCLUSIONS The use of chlorhexidine–alcohol for preoperative skin antisepsis resulted in a significantly lower risk of surgical-site infection after cesarean delivery than did the use of iodine–alcohol. (Funded by the National Institutes of Health and Washington University School of Medicine in St. Louis; ClinicalTrials.gov number, NCT01472549.) PMID:26844840

  6. A randomized trial of intraarterial treatment for acute ischemic stroke.

    PubMed

    Berkhemer, Olvert A; Fransen, Puck S S; Beumer, Debbie; van den Berg, Lucie A; Lingsma, Hester F; Yoo, Albert J; Schonewille, Wouter J; Vos, Jan Albert; Nederkoorn, Paul J; Wermer, Marieke J H; van Walderveen, Marianne A A; Staals, Julie; Hofmeijer, Jeannette; van Oostayen, Jacques A; Lycklama à Nijeholt, Geert J; Boiten, Jelis; Brouwer, Patrick A; Emmer, Bart J; de Bruijn, Sebastiaan F; van Dijk, Lukas C; Kappelle, L Jaap; Lo, Rob H; van Dijk, Ewoud J; de Vries, Joost; de Kort, Paul L M; van Rooij, Willem Jan J; van den Berg, Jan S P; van Hasselt, Boudewijn A A M; Aerden, Leo A M; Dallinga, René J; Visser, Marieke C; Bot, Joseph C J; Vroomen, Patrick C; Eshghi, Omid; Schreuder, Tobien H C M L; Heijboer, Roel J J; Keizer, Koos; Tielbeek, Alexander V; den Hertog, Heleen M; Gerrits, Dick G; van den Berg-Vos, Renske M; Karas, Giorgos B; Steyerberg, Ewout W; Flach, H Zwenneke; Marquering, Henk A; Sprengers, Marieke E S; Jenniskens, Sjoerd F M; Beenen, Ludo F M; van den Berg, René; Koudstaal, Peter J; van Zwam, Wim H; Roos, Yvo B W E M; van der Lugt, Aad; van Oostenbrugge, Robert J; Majoie, Charles B L M; Dippel, Diederik W J

    2015-01-01

    In patients with acute ischemic stroke caused by a proximal intracranial arterial occlusion, intraarterial treatment is highly effective for emergency revascularization. However, proof of a beneficial effect on functional outcome is lacking. We randomly assigned eligible patients to either intraarterial treatment plus usual care or usual care alone. Eligible patients had a proximal arterial occlusion in the anterior cerebral circulation that was confirmed on vessel imaging and that could be treated intraarterially within 6 hours after symptom onset. The primary outcome was the modified Rankin scale score at 90 days; this categorical scale measures functional outcome, with scores ranging from 0 (no symptoms) to 6 (death). The treatment effect was estimated with ordinal logistic regression as a common odds ratio, adjusted for prespecified prognostic factors. The adjusted common odds ratio measured the likelihood that intraarterial treatment would lead to lower modified Rankin scores, as compared with usual care alone (shift analysis). We enrolled 500 patients at 16 medical centers in The Netherlands (233 assigned to intraarterial treatment and 267 to usual care alone). The mean age was 65 years (range, 23 to 96), and 445 patients (89.0%) were treated with intravenous alteplase before randomization. Retrievable stents were used in 190 of the 233 patients (81.5%) assigned to intraarterial treatment. The adjusted common odds ratio was 1.67 (95% confidence interval [CI], 1.21 to 2.30). There was an absolute difference of 13.5 percentage points (95% CI, 5.9 to 21.2) in the rate of functional independence (modified Rankin score, 0 to 2) in favor of the intervention (32.6% vs. 19.1%). There were no significant differences in mortality or the occurrence of symptomatic intracerebral hemorrhage. In patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation, intraarterial treatment administered within 6 hours after stroke onset

  7. Randomized trial of oral teriflunomide for relapsing multiple sclerosis.

    PubMed

    O'Connor, Paul; Wolinsky, Jerry S; Confavreux, Christian; Comi, Giancarlo; Kappos, Ludwig; Olsson, Tomas P; Benzerdjeb, Hadj; Truffinet, Philippe; Wang, Lin; Miller, Aaron; Freedman, Mark S

    2011-10-06

    Teriflunomide is a new oral disease-modifying therapy for relapsing forms of multiple sclerosis. We concluded a randomized trial involving 1088 patients with multiple sclerosis, 18 to 55 years of age, with a score of 0 to 5.5 on the Expanded Disability Status Scale and at least one relapse in the previous year or at least two relapses in the previous 2 years. Patients were randomly assigned (in a 1:1:1 ratio) to placebo, 7 mg of teriflunomide, or 14 mg of teriflunomide once daily for 108 weeks. The primary end point was the annualized relapse rate, and the key secondary end point was confirmed progression of disability for at least 12 weeks. Teriflunomide reduced the annualized relapse rate (0.54 for placebo vs. 0.37 for teriflunomide at either 7 or 14 mg), with relative risk reductions of 31.2% and 31.5%, respectively (P<0.001 for both comparisons with placebo). The proportion of patients with confirmed disability progression was 27.3% with placebo, 21.7% with teriflunomide at 7 mg (P=0.08), and 20.2% with teriflunomide at 14 mg (P=0.03). Both teriflunomide doses were superior to placebo on a range of end points measured by magnetic resonance imaging (MRI). Diarrhea, nausea, and hair thinning were more common with teriflunomide than with placebo. The incidence of elevated alanine aminotransferase levels (≥1 times the upper limit of the normal range) was higher with teriflunomide at 7 mg and 14 mg (54.0% and 57.3%, respectively) than with placebo (35.9%); the incidence of levels that were at least 3 times the upper limit of the normal range was similar in the lower- and higher-dose teriflunomide groups and the placebo group (6.3%, 6.7%, and 6.7%, respectively). Serious infections were reported in 1.6%, 2.5%, and 2.2% of patients in the three groups, respectively. No deaths occurred. Teriflunomide significantly reduced relapse rates, disability progression (at the higher dose), and MRI evidence of disease activity, as compared with placebo. (Funded by Sanofi

  8. Key Items to Get Right When Conducting a Randomized Controlled Trial in Education

    ERIC Educational Resources Information Center

    Coalition for Evidence-Based Policy, 2005

    2005-01-01

    This is a checklist of key items to get right when conducting a randomized controlled trial to evaluate an educational program or practice ("intervention"). It is intended as a practical resource for researchers and sponsors of research, describing items that are often critical to the success of a randomized controlled trial. A significant…

  9. A Randomized Trial of Telephone Psychotherapy and Pharmacotherapy for Depression: Continuation and Durability of Effects

    ERIC Educational Resources Information Center

    Ludman, Evette J.; Simon, Gregory E.; Tutty, Steve; Von Korff, Michael

    2007-01-01

    Randomized trial evidence and expert guidelines are mixed regarding the value of combined pharmacotherapy and psychotherapy as initial treatment for depression. This study describes long-term results of a randomized trial (N = 393) evaluating telephone-based cognitive-behavioral therapy (CBT) plus care management for primary care patients…

  10. A Randomized Trial of Telephone Psychotherapy and Pharmacotherapy for Depression: Continuation and Durability of Effects

    ERIC Educational Resources Information Center

    Ludman, Evette J.; Simon, Gregory E.; Tutty, Steve; Von Korff, Michael

    2007-01-01

    Randomized trial evidence and expert guidelines are mixed regarding the value of combined pharmacotherapy and psychotherapy as initial treatment for depression. This study describes long-term results of a randomized trial (N = 393) evaluating telephone-based cognitive-behavioral therapy (CBT) plus care management for primary care patients…

  11. Randomized controlled trials and challenge trials: design and criterion for validity.

    PubMed

    Sargeant, J M; Kelton, D F; O'Connor, A M

    2014-06-01

    This article is the third of six articles addressing systematic reviews in animal agriculture and veterinary medicine. This article provides an overview of clinical trials, both randomized controlled trials (RCTs) and challenge trials, where the disease outcome is deliberately induced by the investigator. RCTs are not the only study design used in systematic reviews, but are preferred when available as the gold standard for evaluating interventions under real-world conditions. RCTs are planned experiments, which involve diseased or at-risk study subjects and are designed to evaluate interventions (therapeutic treatments or preventive strategies, including antibiotics, vaccines, management practices, dietary changes, management changes or lifestyle changes). Key components of the RCT are the use of one or more comparison (control) groups and investigator control over intervention allocation. Important design features in RCTs include as follows: how the population is selected, approach to allocation of intervention and control group subjects, how allocation is concealed prior to enrolment of study subjects, how outcomes are defined, how allocation to group is concealed (blinding) and how withdrawals from the study are managed. Guidelines for reporting important features of RCTs have been published and are useful tools for writing, reviewing and reading reports of RCTs.

  12. Recruiting to Clinical Trials on the Telephone - a randomized controlled trial.

    PubMed

    Foss, Kim Thestrup; Kjærgaard, Jesper; Stensballe, Lone Graff; Greisen, Gorm

    2016-11-21

    Informed consent is an essential element of clinical research. Obtaining consent, however, may be challenging. The use of the telephone for giving information and obtaining consent may be practical but little formal research has been done. We examined the use of the telephone for the purpose of informing expectant mothers about The Danish Calmette Study; a randomized clinical trial assessing neonatal Bacille Calmette-Guérin vaccination. Expectant mothers received an invitation letter with a Participant Information Sheet about The Danish Calmette Study, the present trial, and a Consent Form. Two to 4 weeks later we contacted the mothers to discuss potential participation in the present trial. At this initial telephone contact, and after consent from the mothers, we randomized expectant mothers to receive the verbal information about The Danish Calmette Study by telephone, or at a face-to-face consultation. The primary outcome was a communication score, consisting of comprehension of information about The Danish Calmette Study and satisfaction with the information process. The outcome was measured using a questionnaire 2 days after the information was provided, and 2.5 months after the birth of the child. The communication score obtained 2 days after information was given was significantly reduced in the telephone group, effect size -0.74 (95% confidence interval (CI), -1.11 to -0.36). The effect sizes of the subscores were -0.87 (95% CI, -1.25 to -0.49) for satisfaction and -0.22 (95% CI, -0.58 to 0.14) for comprehension. The effect sizes were slightly reduced when assessed 2.5 months after the birth. The communication score was reduced in the telephone group. This was due to a reduction in satisfaction, while no difference in the comprehension could be found in comparison to the control group. This may be ethically acceptable as both groups had high satisfaction scores. ClinicalTrials.gov, registered on 5 October 2015 with trial registration number NCT

  13. Nicotine patch preloading for smoking cessation (the preloading trial): study protocol for a randomized controlled trial

    PubMed Central

    2014-01-01

    Background The use of nicotine replacement therapy before quitting smoking is called nicotine preloading. Standard smoking cessation protocols suggest commencing nicotine replacement therapy only on the first day of quitting smoking (quit day) aiming to reduce withdrawal symptoms and craving. However, other, more successful smoking cessation pharmacotherapies are used prior to the quit day as well as after. Nicotine preloading could improve quit rates by reducing satisfaction from smoking prior to quitting and breaking the association between smoking and reward. A systematic literature review suggests that evidence for the effectiveness of preloading is inconclusive and further trials are needed. Methods/Design This is a study protocol for a multicenter, non-blinded, randomized controlled trial based in the United Kingdom, enrolling 1786 smokers who want to quit, funded by the National Institute for Health Research, Health Technology Assessment program, and sponsored by the University of Oxford. Participants will primarily be recruited through general practices and smoking cessation clinics, and randomized (1:1) either to use 21 mg nicotine patches, or not, for four weeks before quitting, whilst smoking as normal. All participants will be referred to receive standard smoking cessation service support. Follow-ups will take place at one week, four weeks, six months and 12 months after quit day. The primary outcome will be prolonged, biochemically verified six-month abstinence. Additional outcomes will include point prevalence abstinence and abstinence of four-week and 12-month duration, side effects, costs of treatment, and markers of potential mediators and moderators of the preloading effect. Discussion This large trial will add substantially to evidence on the effectiveness of nicotine preloading, but also on its cost effectiveness and potential mediators, which have not been investigated in detail previously. A range of recruitment strategies have been

  14. A Randomized Controlled Trial of Storytelling as a Communication Tool

    PubMed Central

    Hartling, Lisa; Scott, Shannon D.; Johnson, David W.; Bishop, Ted; Klassen, Terry P.

    2013-01-01

    Introduction Stories may be an effective tool to communicate with patients because of their ability to engage the reader. Our objective was to evaluate the effectiveness of story booklets compared to standard information sheets for parents of children attending the emergency department (ED) with a child with croup. Methods Parents were randomized to receive story booklets (n=208) or standard information sheets (n=205) during their ED visit. The primary outcome was change in anxiety between triage to ED discharge as measured by the State-Trait Anxiety Inventory. Follow-up telephone interviews were conducted at 1 and 3 days after discharge, then every other day until 9 days (or until resolution of symptoms), and at 1 year. Secondary outcomes included: expected future anxiety, event impact, parental knowledge, satisfaction, decision regret, healthcare utilization, time to symptom resolution. Results There was no significant difference in the primary outcome of change in parental anxiety between recruitment and ED discharge (change of 5 points for the story group vs. 6 points for the comparison group, p=0.78). The story group showed significantly greater decision regret regarding their decision to go to the ED (p<0.001): 6.7% of the story group vs. 1.5% of the comparison group strongly disagreed with the statement “I would go for the same choice if I had to do it over again”. The story group reported shorter time to resolution of symptoms (mean 3.7 days story group vs. 4.0 days comparison group, median 3 days both groups; log rank test, p=0.04). No other outcomes were different between study groups. Conclusions Stories about parent experiences managing a child with croup did not reduce parental anxiety. The story group showed significantly greater decision regret and quicker time to resolution of symptoms. Further research is needed to better understand whether stories can be effective in improving patient-important outcomes. Trial Registration Current Controlled

  15. Review of the randomized clinical stroke rehabilitation trials in 2009

    PubMed Central

    Rabadi, Meheroz H.

    2011-01-01

    Summary Background Recent review of the available evidence on interventions for motor recovery after stroke, showed that improvements in recovery of arm function were seen for constraint-induced movement therapy, electromyographic biofeedback, mental practice with motor imagery, and robotics. Similar improvement in transfer ability or balance were seen with repetitive task training, biofeedback, and training with a moving platform. Walking speed was improved by physical fitness training, high-intensity physiotherapy and repetitive task training. However, most of these trials were small and had design limitations. Material/Methods In this article, randomized control trials (RCT’s) published in 2009 of rehabilitation therapies for acute (≤2 weeks), sub-acute (2 to 12 weeks) and chronic (≥12 weeks) stroke was reviewed. A Medline search was performed to identify all RCT’s in stroke rehabilitation in the year 2009. The search strategy that was used for PubMed is presented in the Appendix 1. The objective was to examine the effectiveness of these treatment modalities in stroke rehabilitation. Results This generated 35 RCT’s under 5 categories which were found and analyzed. The methodological quality was assessed by using the PEDro scale for external and internal validity. Conclusions These trials were primarily efficacy studies. Most of these studies enrolled small numbers of patient which precluded their clinical applicability (limited external validity). However, the constraint induced movement therapy (CIT), regularly used in chronic stroke patients did not improve affected arm-hand function when used in acute stroke patients at ≤4 weeks. Intensive CIT did not lead to motor improvement in arm-hand function. Robotic arm treatment helped decrease motor impairment and improved function in chronic stroke patients only. Therapist provided exercise programs (when self-administered by patients during their off-therapy time in a rehabilitation setting) did improve

  16. The reporting quality of randomized controlled trials in orthodontics.

    PubMed

    Lempesi, Evangelia; Koletsi, Despina; Fleming, Padhraig S; Pandis, Nikolaos

    2014-06-01

    Accurate trial reporting facilitates evaluation and better use of study results. The objective of this article is to investigate the quality of reporting of randomized controlled trials (RCTs) in leading orthodontic journals, and to explore potential predictors of improved reporting. The 50 most recent issues of 4 leading orthodontic journals until November 2013 were electronically searched. Reporting quality assessment was conducted using the modified CONSORT statement checklist. The relationship between potential predictors and the modified CONSORT score was assessed using linear regression modeling. 128 RCTs were identified with a mean modified CONSORT score of 68.97% (SD = 11.09). The Journal of Orthodontics (JO) ranked first in terms of completeness of reporting (modified CONSORT score 76.21%, SD = 10.1), followed by American Journal of Orthodontics and Dentofacial Orthopedics (AJODO) (73.05%, SD = 10.1). Journal of publication (AJODO: β = 10.08, 95% CI: 5.78, 14.38; JO: β = 16.82, 95% CI: 11.70, 21.94; EJO: β = 7.21, 95% CI: 2.69, 11.72 compared to Angle), year of publication (β = 0.98, 95% CI: 0.28, 1.67 for each additional year), region of authorship (Europe: β = 5.19, 95% CI: 1.30, 9.09 compared to Asia/other), statistical significance (significant: β = 3.10, 95% CI: 0.11, 6.10 compared to non-significant) and methodologist involvement (involvement: β = 5.60, 95% CI: 1.66, 9.54 compared to non-involvement) were all significant predictors of improved modified CONSORT scores in the multivariable model. Additionally, median overall Jadad score was 2 (IQR = 2) across journals, with JO (median = 3, IQR = 1) and AJODO (median = 3, IQR = 2) presenting the highest score values. The reporting quality of RCTs published in leading orthodontic journals is considered suboptimal in various CONSORT areas. This may have a bearing in trial result interpretation and use in clinical decision making and evidence- based orthodontic treatment interventions. Copyright

  17. A post-trial assessment of factors influencing study drug adherence in a randomized biomedical HIV-1 prevention trial

    PubMed Central

    Jacob, Shevin T.; Baeten, Jared M.; Hughes, James P.; Peinado, Jesús; Wang, Jing; Sanchez, Jorge; Reid, Stewart E.; Delany-Moretlwe, Sinead; Cowan, Frances; Fuchs, Jonathan; Koblin, Beryl; Griffith, Sam; Wald, Anna; Celum, Connie

    2010-01-01

    High adherence and maintenance of blinding are critical for placebo-controlled efficacy trials of HIV-1 biomedical prevention strategies. We assessed adherence to study drug and factors affecting adherence, including perceived randomization group, in a post-trial questionnaire of participants who completed HPTN 039, a randomized, placebo-controlled trial of HSV-2 suppression with twice-daily acyclovir to reduce HIV-1 acquisition. Of the 3172 trial participants, 2003 (63%) completed the post-trial questionnaire. Of these 2003, 72% reported missing a dose of study drug less than twice a week. Study drug adherence was not compromised by perceived randomization or genital ulcer symptoms during the study. Alcohol use was cited as an adherence barrier in some populations. Assessment of study drug adherence during and at the end of trials can evaluate perceptions of randomization and adherence by randomization arm, help to better understand barriers to and motivations for adherence, and develop interventions to increase adherence for future trials. PMID:21104007

  18. The Tinnitus Retraining Therapy Trial (TRTT): study protocol for a randomized controlled trial.

    PubMed

    Scherer, Roberta W; Formby, Craig; Gold, Susan; Erdman, Sue; Rodhe, Charles; Carlson, Michele; Shade, Dave; Tucker, Melanie; Sensinger, Lee McCaffrey; Hughes, Gordon; Conley, George S; Downey, Naomi; Eades, Cynthia; Jylkka, Margaret; Haber-Perez, Ada; Harper, Courtney; Russell, Shoshannah Kantor; Sierra-Irizarry, Benigno; Sullivan, Mark

    2014-10-15

    Subjective tinnitus is the perception of sound in the absence of a corresponding external sound for which there is no known medical etiology. For a minority of individuals with tinnitus, the condition impacts their ability to lead a normal lifestyle and is severely debilitating. There is no known cure for tinnitus, so current therapy focuses on reducing the effect of tinnitus on the patient's quality of life. Tinnitus retraining therapy (TRT) uses nonpsychiatric tinnitus-specific educational counseling and sound therapy in a habituation-based protocol to reduce the patient's tinnitus-evoked negative reaction to, and awareness of, the tinnitus, with the ultimate goal of reducing the tinnitus impact on the patient's quality of life. Some studies support the efficacy of TRT, but no trial to date has compared TRT with the current standard of care or evaluated the separate contributions of TRT counseling and sound therapy. The Tinnitus Retraining Therapy Trial (TRTT) is a randomized, double-blind, placebo-controlled, multicenter trial for individuals with intolerable tinnitus. The TRTT is enrolling active-duty and retired military personnel and their dependents with functionally adequate hearing sensitivity and severe tinnitus at US Air Force, Navy, and Army medical centers. Eligible study participants are randomized to TRT, partial TRT, or standard care to determine the efficacy of TRT and its components (TRT counseling and sound therapy). The primary outcome is change in score on the Tinnitus Questionnaire assessed longitudinally between baseline and follow-up (3, 6, 12, and 18 months following treatment). Secondary outcomes include subscale score changes in the Tinnitus Questionnaire, overall and subscale score changes in the Tinnitus Functional Index and Tinnitus Handicap Inventory, and change in the visual analog scale of the TRT Interview Form. Audiological outcomes include tinnitus pitch and loudness match and measures of loudness discomfort levels. The incidence

  19. Music intervention during daily weaning trials-A 6 day prospective randomized crossover trial.

    PubMed

    Liang, Zhan; Ren, Dianxu; Choi, JiYeon; Happ, Mary Beth; Hravnak, Marylyn; Hoffman, Leslie A

    2016-12-01

    To examine the effect of patient-selected music intervention during daily weaning trials for patients on prolonged mechanical ventilation. Using a crossover repeated measures design, patients were randomized to music vs no music on the first intervention day. Provision of music was alternated for 6 days, resulting in 3 music and 3 no music days. During weaning trials on music days, data were obtained for 30min prior to music listening and continued for 60min while patients listened to selected music (total 90min). On no music days, data were collected for 90min. Outcome measures were heart rate (HR), respiratory rate (RR), oxygen saturation (SpO2), blood pressure (BP), dyspnea and anxiety assessed with a visual analog scale (VAS-D, VAS-A) and weaning duration (meanh per day on music and non-music days). Of 31 patients randomized, 23 completed the 6-day intervention. When comparisons were made between the 3 music and 3 no music days, there were significant decreases in RR and VAS-D and a significant increase in daily weaning duration on music days (p<0.05). A multivariate mixed-effects model analysis that included patients who completed ≥2 days of the intervention (n=28) demonstrated significant decreases in HR, RR, VAS-A, and VAS-D and a significant increase in daily weaning duration on music days (p<0.05). Providing patient selected music during daily weaning trials is a simple, low-cost, potentially beneficial intervention for patients on prolonged mechanical ventilation. Further study is indicated to test ability of this intervention to promote weaning success and benefits earlier in the weaning process. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Rural providers' access to online resources: a randomized controlled trial

    PubMed Central

    Hall, Laura J.; McElfresh, Karen R.; Warner, Teddy D.; Stromberg, Tiffany L.; Trost, Jaren; Jelinek, Devin A.

    2016-01-01

    Objective The research determined the usage and satisfaction levels with one of two point-of-care (PoC) resources among health care providers in a rural state. Methods In this randomized controlled trial, twenty-eight health care providers in rural areas were stratified by occupation and region, then randomized into either the DynaMed or the AccessMedicine study arm. Study participants were physicians, physician assistants, and nurses. A pre- and post-study survey measured participants' attitudes toward different information resources and their information-seeking activities. Medical student investigators provided training and technical support for participants. Data analyses consisted of analysis of variance (ANOVA), paired t tests, and Cohen's d statistic to compare pre- and post-study effects sizes. Results Participants in both the DynaMed and the AccessMedicine arms of the study reported increased satisfaction with their respective PoC resource, as expected. Participants in both arms also reported that they saved time in finding needed information. At baseline, both arms reported too little information available, which increased to “about right amounts of information” at the completion of the study. DynaMed users reported a Cohen's d increase of +1.50 compared to AccessMedicine users' reported use of 0.82. DynaMed users reported d2 satisfaction increases of 9.48 versus AccessMedicine satisfaction increases of 0.59 using a Cohen's d. Conclusion Participants in the DynaMed arm of the study used this clinically oriented PoC more heavily than the users of the textbook-based AccessMedicine. In terms of user satisfaction, DynaMed users reported higher levels of satisfaction than the users of AccessMedicine. PMID:26807050

  1. School-Located Influenza Vaccinations: A Randomized Trial.

    PubMed

    Szilagyi, Peter G; Schaffer, Stanley; Rand, Cynthia M; Vincelli, Phyllis; Eagan, Ashley; Goldstein, Nicolas P N; Hightower, A Dirk; Younge, Mary; Blumkin, Aaron; Albertin, Christina S; Yoo, Byung-Kwang; Humiston, Sharon G

    2016-11-01

    Assess impact of offering school-located influenza vaccination (SLIV) clinics using both Web-based and paper consent upon overall influenza vaccination rates among elementary school children. We conducted a cluster-randomized trial (stratified by suburban/urban districts) in upstate New York in 2014-2015. We randomized 44 elementary schools, selected similar pairs of schools within districts, and allocated schools to SLIV versus usual care (control). Parents of children at SLIV schools were sent information and vaccination consent forms via e-mail, backpack fliers, or both (depending on school preferences) regarding school vaccine clinics. Health department nurses conducted vaccine clinics and billed insurers. For all children registered at SLIV/control schools, we compared receipt of influenza vaccination anywhere (primary outcome). The 44 schools served 19 776 eligible children in 2014-2015. Children in SLIV schools had higher influenza vaccination rates than children in control schools county-wide (54.1% vs 47.4%, P < .001) and in suburban (61.9% vs 53.6%, P < .001) and urban schools (43.9% vs 39.2%; P < .001). Multivariate analyses (controlling for age, grade, vaccination in previous season) confirmed bivariate findings. Among parents who consented for SLIV, nearly half of those notified by backpack fliers and four-fifths of those notified by e-mail consented online. In suburban districts, SLIV did not substitute for primary care influenza vaccination. In urban schools, some substitution occurred. SLIV raised seasonal influenza vaccination rates county-wide and in both suburban and urban settings. SLIV did not substitute for primary care vaccinations in suburban settings where pediatricians often preorder influenza vaccine but did substitute somewhat in urban settings. Copyright © 2016 by the American Academy of Pediatrics.

  2. Chronic Fatigue Self- Management in Primary Care: A Randomized Trial

    PubMed Central

    Friedberg, Fred; Napoli, Anthony; Coronel, Janna; Adamowicz, Jenna; Seva, Viktoria; Caikauskaite, Indre; Ngan, Man Chi; Chang, Jeremy; Meng, Hongdao

    2013-01-01

    Objective To assess the efficacy of brief fatigue self-management for medically unexplained chronic fatigue (UCF) and chronic fatigue syndrome (CFS) in primary care. Methods A randomized controlled design was used wherein 111 patients with UCF or CFS were randomly assigned to: two sessions of fatigue self-management (FSM), two sessions of symptom monitoring support (attention control; AC), or a usual care control condition (UC). Participants were assessed at baseline and at 3- and 12-months post-treatment. The primary outcome, the Fatigue Severity Scale, measured fatigue impact on functioning. Analysis was by intention-to-treat (multiple imputation) and also by per protocol. Results A group by time interaction across the 15 month trial showed significantly greater reductions in fatigue impact in the FSM group in comparison to the AC group (p< .023) and the UC group (p< .013). Medium effect sizes for reduced fatigue impact in the FSM group were found in comparison with the AC group (d=.46) and the UC group (d=.40). The per protocol analysis revealed large effect sizes for the same comparisons. Clinically significant decreases in fatigue impact were found for 53% of participants in the FSM condition, 14% in the AC condition, and 17% in the UC condition. Dropout rates at the 12 month follow-up were high (42%–53%) perhaps attributable to the burden of monthly phone calls to assess health care utilization. Conclusion A brief self-management intervention for patients with UCF or CFS appeared to be clinically effective for reducing the impact of fatigue on functioning. PMID:23922399

  3. A randomized trial of a telephone care-management strategy.

    PubMed

    Wennberg, David E; Marr, Amy; Lang, Lance; O'Malley, Stephen; Bennett, George

    2010-09-23

    Studies have shown that telephone interventions designed to promote patients' self-management skills and improve patient-physician communication can increase patients' satisfaction and their use of preventive services. The effect of such a strategy on health care costs remains controversial. We conducted a stratified, randomized study of 174,120 subjects to assess the effect of a telephone-based care-management strategy on medical costs and resource utilization. Health coaches contacted subjects with selected medical conditions and predicted high health care costs to instruct them about shared decision making, self-care, and behavioral change. The subjects were randomly assigned to either a usual-support group or an enhanced-support group. Although the same telephone intervention was delivered to the two groups, a greater number of subjects in the enhanced-support group were made eligible for coaching through the lowering of cutoff points for predicted future costs and expansion of the number of qualifying health conditions. Primary outcome measures at 1 year were total medical costs and number of hospital admissions. At baseline, medical costs and resource utilization were similar in the two groups. After 12 months, 10.4% of the enhanced-support group and 3.7% of the usual-support group received the telephone intervention. The average monthly medical and pharmacy costs per person in the enhanced-support group were 3.6% ($7.96) lower than those in the usual-support group ($213.82 vs. $221.78, P=0.05); a 10.1% reduction in annual hospital admissions (P<0.001) accounted for the majority of savings. The cost of this intervention program was less than $2.00 per person per month. A targeted telephone care-management program was successful in reducing medical costs and hospitalizations in this population-based study. (Funded by Health Dialog Services; ClinicalTrials.gov number, NCT00793260.)

  4. A Randomized Controlled Trial of Mentoring Interventions for Underrepresented Minorities

    PubMed Central

    Lewis, Vivian; Martina, Camille A.; McDermott, Michael P.; Trief, Paula; Goodman, Steven R.; Morse, Gene D.; LaGuardia, Jennifer G.; Sharp, Daryl; Ryan, Richard M.

    2015-01-01

    Purpose To conduct a randomized controlled trial (RCT) to evaluate the effects of different mentoring interventions on the basic psychological need satisfaction of underrepresented minorities and women in academia. Method Participants were 150 mentor/protégé dyads from three academic medical centers and eight other colleges and universities in western and central New York, randomized from 2010–2013 into: mentor training (using principles of self-determination theory); peer mentoring for protégés; mentor training and peer mentoring for protégés combined; or control/usual practice. Protégé participants were graduate students, fellows and junior faculty who were from underrepresented groups based on race, ethnicity, gender, or disability. The primary analysis was a comparison of intervention effects on changes in protégés’ satisfaction of their basic psychological needs (competence, autonomy and relatedness) with their mentor. They completed a well-validated, online questionnaire every 2 months for 1 year. Results There was no significant effect at the end of 1 year of either mentor training or peer mentoring on protégés’ psychological basic need satisfaction with mentor specifically or at work in general. Exploratory analyses showed a significant effect of the mentor-based intervention on the protégés’ overall psychological need satisfaction with their mentor at 2 months, the time point closest to completing mentor training. Conclusions This RCT showed a potential short-term effect of mentor training on changing basic psychological need satisfaction of underrepresented scholars with their mentors. Despite the lack of sustained effect of either mentor training or peer mentoring, these short-term changes suggest feasibility and potential for future study. PMID:26717501

  5. Classroom and simulation team training: a randomized controlled trial.

    PubMed

    Clay-Williams, Robyn; McIntosh, Catherine A; Kerridge, Ross; Braithwaite, Jeffrey

    2013-07-01

    To test the hypotheses that classroom and simulation-based crew resource management (CRM) training interventions improve teamwork attitudes and behaviours of participants and that classroom training combined with simulation-based training provide synergistic improvements. A randomized controlled trial. Area Health Service in New South Wales, Australia. A total of 157 doctors, nurses and midwives randomized into one of four groups, consisting of three intervention groups and a control group. One-day CRM-based classroom course; one-day CRM style simulation-based training or classroom training followed by simulation-based training. Pre- and post-test quantitative participant teamwork attitudes, and post-test quantitative trainee reactions, knowledge and behaviour. Ninety-four doctors, nurses and midwives completed pre-intervention attitude questionnaires and 60 clinicians completed post-intervention assessments. No positive changes in teamwork attitudes were found associated with classroom or simulation training. Positive changes were found in knowledge (mean difference 1.50, 95% confidence interval (CI) 0.58-2.43, P = 0.002), self-assessed teamwork behaviour (mean difference 2.69, 95% CI 0.90-6.13, P = 0.009) and independently observed teamwork behaviour (mean difference 2.30, 95% CI 0.30-4.30, P = 0.027) when classroom-only trained group was compared with control; however, these changes were not found in the group that received classroom followed by simulation training. Classroom-based training alone resulted in improvements in participant knowledge and observed teamwork behaviour. The study found no additional impact of simulation training.

  6. Snoezelen Room and Childbirth Outcome: A Randomized Clinical Trial.

    PubMed

    Jamshidi Manesh, Mansoureh; Kalati, Mahnaz; Hosseini, Fatemeh

    2015-05-01

    One of the strategies for a good outcome and pain free childbearing is to design the delivery room. The aim of this study was to evaluate the effects of snoezelen room on childbearing outcome such as pain intensity, duration of labor, and perinea status in nulliparous women. This study was a randomized controlled clinical trial consists of 100 childbearing women. They were randomly divided into 2 groups. The experimental group went to snoezelen room when their cervix dilation was 4 cm, while the control group went to physiologic delivery room with the same cervix dilation. The mean ± SD of VAS (Visual Analogue Scale) pain intensity of the experimental and control groups before the intervention were 5.1 ± 1.95 and 5.58 ± 1.62, respectively (P = 0.13). The mean ± SD of VAS pain intensity scores of the experimental and control groups after 3 hours spending in their assigned rooms were 5.26 ± 0.86 and 9.56 ± 1.48, respectively (P = 0.01). The mean ± SD of the first stage scores of the experimental and control groups were 6.95 ± 0.97 and 8.41 ± 0.67, respectively (P = 0.042). About 92% of participants' intervention vs. 66% of control participants had perinea laceration (P = 0.041). According to the findings of the present study, distracting senses in snoezelen room decreases mother's pain intensity, the length of labor, and incidence of episiotomy.

  7. Snoezelen Room and Childbirth Outcome: A Randomized Clinical Trial

    PubMed Central

    Jamshidi Manesh, Mansoureh; Kalati, Mahnaz; Hosseini, Fatemeh

    2015-01-01

    Background: One of the strategies for a good outcome and pain free childbearing is to design the delivery room. Objectives: The aim of this study was to evaluate the effects of snoezelen room on childbearing outcome such as pain intensity, duration of labor, and perinea status in nulliparous women. Patients and Methods: This study was a randomized controlled clinical trial consists of 100 childbearing women. They were randomly divided into 2 groups. The experimental group went to snoezelen room when their cervix dilation was 4 cm, while the control group went to physiologic delivery room with the same cervix dilation. Results: The mean ± SD of VAS (Visual Analogue Scale) pain intensity of the experimental and control groups before the intervention were 5.1 ± 1.95 and 5.58 ± 1.62, respectively (P = 0.13). The mean ± SD of VAS pain intensity scores of the experimental and control groups after 3 hours spending in their assigned rooms were 5.26 ± 0.86 and 9.56 ± 1.48, respectively (P = 0.01). The mean ± SD of the first stage scores of the experimental and control groups were 6.95 ± 0.97 and 8.41 ± 0.67, respectively (P = 0.042). About 92% of participants’ intervention vs. 66% of control participants had perinea laceration (P = 0.041). Conclusions: According to the findings of the present study, distracting senses in snoezelen room decreases mother’s pain intensity, the length of labor, and incidence of episiotomy. PMID:26082849

  8. Dextrose Prolotherapy for Knee Osteoarthritis: A Randomized Controlled Trial

    PubMed Central

    Rabago, David; Patterson, Jeffrey J.; Mundt, Marlon; Kijowski, Richard; Grettie, Jessica; Segal, Neil A.; Zgierska, Aleksandra

    2013-01-01

    PURPOSE Knee osteoarthritis is a common, debilitating chronic disease. Prolotherapy is an injection therapy for chronic musculoskeletal pain. We conducted a 3-arm, blinded (injector, assessor, injection group participants), randomized controlled trial to assess the efficacy of prolotherapy for knee osteoarthritis. METHODS Ninety adults with at least 3 months of painful knee osteoarthritis were randomized to blinded injection (dextrose prolotherapy or saline) or at-home exercise. Extra- and intra-articular injections were done at 1, 5, and 9 weeks with as-needed additional treatments at weeks 13 and 17. Exercise participants received an exercise manual and in-person instruction. Outcome measures included a composite score on the Western Ontario McMaster University Osteoarthritis Index (WOMAC; 100 points); knee pain scale (KPS; individual knee), post-procedure opioid medication use, and participant satisfaction. Intention-to-treat analysis using analysis of variance was used. RESULTS No baseline differences existed between groups. All groups reported improved composite WOMAC scores compared with baseline status (P <.01) at 52 weeks. Adjusted for sex, age, and body mass index, WOMAC scores for patients receiving dextrose prolotherapy improved more (P <.05) at 52 weeks than did scores for patients receiving saline and exercise (score change: 15.3 ± 3.5 vs 7.6 ± 3.4, and 8.2 ± 3.3 points, respectively) and exceeded the WOMAC-based minimal clinically important difference. Individual knee pain scores also improved more in the prolotherapy group (P = .05). Use of prescribed postprocedure opioid medication resulted in rapid diminution of injection-related pain. Satisfaction with prolotherapy was high. There were no adverse events. CONCLUSIONS Prolotherapy resulted in clinically meaningful sustained improvement of pain, function, and stiffness scores for knee osteoarthritis compared with blinded saline injections and at-home exercises. PMID:23690322

  9. Dextrose prolotherapy for knee osteoarthritis: a randomized controlled trial.

    PubMed

    Rabago, David; Patterson, Jeffrey J; Mundt, Marlon; Kijowski, Richard; Grettie, Jessica; Segal, Neil A; Zgierska, Aleksandra

    2013-01-01

    Knee osteoarthritis is a common, debilitating chronic disease. Prolotherapy is an injection therapy for chronic musculoskeletal pain. We conducted a 3-arm, blinded (injector, assessor, injection group participants), randomized controlled trial to assess the efficacy of prolotherapy for knee osteoarthritis. Ninety adults with at least 3 months of painful knee osteoarthritis were randomized to blinded injection (dextrose prolotherapy or saline) or at-home exercise. Extra- and intra-articular injections were done at 1, 5, and 9 weeks with as-needed additional treatments at weeks 13 and 17. Exercise participants received an exercise manual and in-person instruction. Outcome measures included a composite score on the Western Ontario McMaster University Osteoarthritis Index (WOMAC; 100 points); knee pain scale (KPS; individual knee), post-procedure opioid medication use, and participant satisfaction. Intention-to-treat analysis using analysis of variance was used. No baseline differences existed between groups. All groups reported improved composite WOMAC scores compared with baseline status (P <.01) at 52 weeks. Adjusted for sex, age, and body mass index, WOMAC scores for patients receiving dextrose prolotherapy improved more (P <.05) at 52 weeks than did scores for patients receiving saline and exercise (score change: 15.3 ± 3.5 vs 7.6 ± 3.4, and 8.2 ± 3.3 points, respectively) and exceeded the WOMAC-based minimal clinically important difference. Individual knee pain scores also improved more in the prolotherapy group (P = .05). Use of prescribed postprocedure opioid medication resulted in rapid diminution of injection-related pain. Satisfaction with prolotherapy was high. There were no adverse events. Prolotherapy resulted in clinically meaningful sustained improvement of pain, function, and stiffness scores for knee osteoarthritis compared with blinded saline injections and at-home exercises.

  10. Randomized clinical trial of chewing gum after laparoscopic colorectal resection.

    PubMed

    Shum, N F; Choi, H K; Mak, J C K; Foo, D C C; Li, W C; Law, W L

    2016-10-01

    Chewing gum may enhance intestinal motility after surgery. This trial studied whether chewing gum could lead to a further reduction in ileus in patients who had a laparoscopic colorectal resection and followed an enhanced recovery programme. Patients undergoing laparoscopic colorectal resection were randomized to a control or intervention group. Patients in the control group received a standardized recovery programme. Patients in the intervention group were, in addition, given chewing gum three times daily from day 1 until discharge. Primary outcome measures were time to first flatus and first bowel motion. Time to feeling hungry and hospital stay were secondary outcome measures. Forty-one patients were randomized into each group. Thirty-seven patients underwent rectal resection and 45 had a colonic resection. Time to passage of flatus was shorter (18 versus 34 h; P = 0·007), first bowel motion occurred earlier (19 versus 44 h; P = 0·001) and time to feeling hungry was earlier (16 versus 25 h; P = 0·001) in the intervention group. There was no difference in the duration of hospital stay (5 days in the intervention group versus 5·5 days in the control group). Subgroup analyses revealed that the benefits of chewing gum were clearer in patients who had a colonic resection, with a shorter time to first flatus (20 versus 35 h; P = 0·043), first bowel motion (19 versus 53 h; P = 0·014) and feeling hungry (14 versus 40 h; P = 0·001). No adverse events were attributed to chewing gum. Chewing gum is a simple intervention that speeds intestinal transit in patients managed with a recovery programme after laparoscopic colorectal resection. NCT02419586 (https://clinicaltrials.gov/). © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

  11. Eating marshmallows reduces ileostomy output: a randomized crossover trial.

    PubMed

    Clarebrough, E; Guest, G; Stupart, D

    2015-12-01

    Anecdotally, many ostomates believe that eating marshmallows can reduce ileostomy effluent. There is a plausible mechanism for this, as the gelatine contained in marshmallows may thicken small bowel fluid, but there is currently no evidence that this is effective. This was a randomized crossover trial. Adult patients with well-established ileostomies were included. Ileostomy output was measured for 1 week during which three marshmallows were consumed three times daily, and for one control week where marshmallows were not eaten. There was a 2-day washout period. Patients were randomly allocated to whether the control or intervention week occurred first. In addition, a questionnaire was administered regarding patient's subjective experience of their ileostomy function. Thirty-one participants were recruited; 28 completed the study. There was a median reduction in ileostomy output volume of 75 ml per day during the study period (P = 0.0054, 95% confidence interval 23.4-678.3) compared with the control week. Twenty of 28 subjects (71%) experienced a reduction in their ileostomy output, two had no change and six reported an increase. During the study period, participants reported fewer ileostomy bag changes (median five per day vs six in the control period, P = 0.0255). Twenty of 28 (71%) reported that the ileostomy effluent was thicker during the study week (P = 0.023). Overall 19 (68%) participants stated they would use marshmallows in the future if they wanted to reduce or thicken their ileostomy output. Eating marshmallows leads to a small but statistically significant reduction in ileostomy output. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

  12. Sentence retrieval for abstracts of randomized controlled trials

    PubMed Central

    2009-01-01

    Background The practice of evidence-based medicine (EBM) requires clinicians to integrate their expertise with the latest scientific research. But this is becoming increasingly difficult with the growing numbers of published articles. There is a clear need for better tools to improve clinician's ability to search the primary literature. Randomized clinical trials (RCTs) are the most reliable source of evidence documenting the efficacy of treatment options. This paper describes the retrieval of key sentences from abstracts of RCTs as a step towards helping users find relevant facts about the experimental design of clinical studies. Method Using Conditional Random Fields (CRFs), a popular and successful method for natural language processing problems, sentences referring to Intervention, Participants and Outcome Measures are automatically categorized. This is done by extending a previous approach for labeling sentences in an abstract for general categories associated with scientific argumentation or rhetorical roles: Aim, Method, Results and Conclusion. Methods are tested on several corpora of RCT abstracts. First structured abstracts with headings specifically indicating Intervention, Participant and Outcome Measures are used. Also a manually annotated corpus of structured and unstructured abstracts is prepared for testing a classifier that identifies sentences belonging to each category. Results Using CRFs, sentences can be labeled for the four rhetorical roles with F-scores from 0.93–0.98. This outperforms the use of Support Vector Machines. Furthermore, sentences can be automatically labeled for Intervention, Participant and Outcome Measures, in unstructured and structured abstracts where the section headings do not specifically indicate these three topics. F-scores of up to 0.83 and 0.84 are obtained for Intervention and Outcome Measure sentences. Conclusion Results indicate that some of the methodological elements of RCTs are identifiable at the sentence

  13. Physician Communication Training and Parental Vaccine Hesitancy: A Randomized Trial.

    PubMed

    Henrikson, Nora B; Opel, Douglas J; Grothaus, Lou; Nelson, Jennifer; Scrol, Aaron; Dunn, John; Faubion, Todd; Roberts, Michele; Marcuse, Edgar K; Grossman, David C

    2015-07-01

    Physicians have a major influence on parental vaccine decisions. We tested a physician-targeted communication intervention designed to (1) reduce vaccine hesitancy in mothers of infants seen by trained physicians and (2) increase physician confidence in communicating about vaccines. We conducted a community-based, clinic-level, 2-arm cluster randomized trial in Washington State. Intervention clinics received physician-targeted communications training. We enrolled mothers of healthy newborns from these clinics at the hospital of birth. Mothers and physicians were surveyed at baseline and 6 months. The primary outcome was maternal vaccine hesitancy measured by Parental Attitudes on Childhood Vaccines score; secondary outcome was physician self-efficacy in communicating with parents by using 3 vaccine communication domains. We enrolled 56 clinics and 347 mothers. We conducted intervention trainings at 30 clinics, reaching 67% of eligible physicians; 26 clinics were randomized to the control group. Maternal vaccine hesitancy at baseline and follow-up changed from 9.8% to 7.5% in the intervention group and 12.6% to 8.0% in the control group. At baseline, groups were similar on all variables except maternal race and ethnicity. The intervention had no detectable effect on maternal vaccine hesitancy (adjusted odds ratio 1.22, 95% confidence interval 0.47-2.68). At follow-up, physician self-efficacy in communicating with parents was not significantly different between intervention and control groups. This physician-targeted communication intervention did not reduce maternal vaccine hesitancy or improve physician self-efficacy. Research is needed to identify physician communication strategies effective at reducing parental vaccine hesitancy in the primary care setting. Copyright © 2015 by the American Academy of Pediatrics.

  14. A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus.

    PubMed

    Revello, Maria Grazia; Lazzarotto, Tiziana; Guerra, Brunella; Spinillo, Arsenio; Ferrazzi, Enrico; Kustermann, Alessandra; Guaschino, Secondo; Vergani, Patrizia; Todros, Tullia; Frusca, Tiziana; Arossa, Alessia; Furione, Milena; Rognoni, Vanina; Rizzo, Nicola; Gabrielli, Liliana; Klersy, Catherine; Gerna, Giuseppe

    2014-04-03

    Congenital infection with human cytomegalovirus (CMV) is a major cause of morbidity and mortality. In an uncontrolled study published in 2005, administration of CMV-specific hyperimmune globulin to pregnant women with primary CMV infection significantly reduced the rate of intrauterine transmission, from 40% to 16%. We evaluated the efficacy of hyperimmune globulin in a phase 2, randomized, placebo-controlled, double-blind study. A total of 124 pregnant women with primary CMV infection at 5 to 26 weeks of gestation were randomly assigned within 6 weeks after the presumed onset of infection to receive hyperimmune globulin or placebo every 4 weeks until 36 weeks of gestation or until detection of CMV in amniotic fluid. The primary end point was congenital infection diagnosed at birth or by means of amniocentesis. A total of 123 women could be evaluated in the efficacy analysis (1 woman in the placebo group withdrew). The rate of congenital infection was 30% (18 fetuses or infants of 61 women) in the hyperimmune globulin group and 44% (27 fetuses or infants of 62 women) in the placebo group (a difference of 14 percentage points; 95% confidence interval, -3 to 31; P=0.13). There was no significant difference between the two groups or, within each group, between the women who transmitted the virus and those who did not, with respect to levels of virus-specific antibodies, T-cell-mediated immune response, or viral DNA in the blood. The clinical outcome of congenital infection at birth was similar in the two groups. The number of obstetrical adverse events was higher in the hyperimmune globulin group than in the placebo group (13% vs. 2%). In this study involving 123 women who could be evaluated, treatment with hyperimmune globulin did not significantly modify the course of primary CMV infection during pregnancy. (Funded by Agenzia Italiana del Farmaco; CHIP ClinicalTrials.gov number, NCT00881517; EudraCT no. 2008-006560-11.).

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

    USDA-ARS?s Scientific Manuscript database

    Recruitment of participants to clinical trials remains a significant challenge, especially for research addressing topics of a sensitive nature such as fecal incontinence (FI). The Fiber Study, a randomized controlled trial on symptom management for FI, successfully enrolled 189 community-living adu...

  16. A Randomized Clinical Trial of Allopregnanolone for the Treatment of Severe Traumatic Brain Injury

    DTIC Science & Technology

    2014-10-01

    mortality in adults with moderate and severe TBI. A Phase 2, adaptive, two-stage, placebo controlled, double blind, randomized clinical trial is being...been manufactured GMP for this trial. Intravenous product solutions have been developed. Subjects are being allocated to 3 dosing levels (1) placebo ...adaptive, two-stage, placebo controlled, double blind, randomized clinical trial. The primary objective is to determine in adults with moderate or severe

  17. Partner randomized controlled trial: study protocol and coaching intervention.

    PubMed

    Garbutt, Jane M; Highstein, Gabrielle; Yan, Yan; Strunk, Robert C

    2012-04-02

    Many children with asthma live with frequent symptoms and activity limitations, and visits for urgent care are common. Many pediatricians do not regularly meet with families to monitor asthma control, identify concerns or problems with management, or provide self-management education. Effective interventions to improve asthma care such as small group training and care redesign have been difficult to disseminate into office practice. This paper describes the protocol for a randomized controlled trial (RCT) to evaluate a 12-month telephone-coaching program designed to support primary care management of children with persistent asthma and subsequently to improve asthma control and disease-related quality of life and reduce urgent care events for asthma care. Randomization occurred at the practice level with eligible families within a practice having access to the coaching program or to usual care. The coaching intervention was based on the transtheoretical model of behavior change. Targeted behaviors included 1) effective use of controller medications, 2) effective use of rescue medications and 3) monitoring to ensure optimal control. Trained lay coaches provided parents with education and support for asthma care, tailoring the information provided and frequency of contact to the parent's readiness to change their child's day-to-day asthma management. Coaching calls varied in frequency from weekly to monthly. For each participating family, follow-up measurements were obtained at 12- and 24-months after enrollment in the study during a telephone interview. The primary outcomes were the mean change in 1) the child's asthma control score, 2) the parent's quality of life score, and 3) the number of urgent care events assessed at 12 and 24 months. Secondary outcomes reflected adherence to guideline recommendations by the primary care pediatricians and included the proportion of children prescribed controller medications, having maintenance care visits at least twice a year

  18. Electroacupuncture for Primary Insomnia: A Randomized Controlled Trial

    PubMed Central

    Yeung, Wing-Fai; Chung, Ka-Fai; Zhang, Shi-Ping; Yap, Tuan-Gee; Law, Andrew C.K.

    2009-01-01

    for insomnia. Citation: Yeung WF; Chung KF; Zhang SP; Yap TG; Law ACK. Electroacupuncture for primary insomnia: a randomized controlled trial. SLEEP 2009;32(8):1039-1047. PMID:19725255

  19. REDUCING SYMPTOM LIMITATIONS: A COGNITIVE BEHAVIORAL INTERVENTION RANDOMIZED TRIAL

    PubMed Central

    DOORENBOS, ARDITH; GIVEN, BARBARA; GIVEN, CHARLES; VERBITSKY, NATALYA; CIMPRICH, BERNADINE; MCCORKLE, RUTH

    2007-01-01

    SUMMARY Until now, little research has been conducted examining the reactive dimension, or the degree to which a symptom limits an individual’s life, in a multiplicity of symptoms. This research examines how problem-solving therapy organizes an intervention to decrease symptom limitations. The purpose was threefold: to determine if a cognitive behavioral intervention decreases the impact of symptom limitations among individuals newly diagnosed with cancer, who are receiving chemotherapy; to determine, after adjusting for covariates, how symptom limitations change over time; and to describe which symptoms are most limiting. This randomized control trial was conducted in two comprehensive and four community cancer centers. Two hundred thirty-seven individuals, aged 31–87, newly diagnosed with solid tumor cancers, participated. The experimental group (118 individuals) received a 10-contact, 18-week cognitive behavioral intervention focused on cancer- and chemotherapy-related symptoms. The control group (119 individuals) received conventional care. Interviews occurred at baseline, 10, 20, and 32 weeks. Data analysis used a two-level hierarchical linear model. Participants receiving the cognitive behavioral intervention had lower scores of symptom limitation than did participants in the control group. At the onset of the study, younger patients reported more symptom limitations than their older counterparts; however, this was reversed by the end of the study. The cognitive behavioral intervention was key to decreasing symptom limitations. Findings also suggest that nursing interventions may be particularly helpful to younger individuals in managing cancer-related symptom limitations. PMID:15643674

  20. Reducing symptom limitations: a cognitive behavioral intervention randomized trial.

    PubMed

    Doorenbos, Ardith; Given, Barbara; Given, Charles; Verbitsky, Natalya; Cimprich, Bernadine; McCorkle, Ruth

    2005-07-01

    Until now, little research has been conducted examining the reactive dimension, or the degree to which a symptom limits an individual's life, in a multiplicity of symptoms. This research examines how problem-solving therapy organizes an intervention to decrease symptom limitations. The purpose was threefold: to determine if a cognitive behavioral intervention decreases the impact of symptom limitations among individuals newly diagnosed with cancer, who are receiving chemotherapy; to determine, after adjusting for covariates, how symptom limitations change over time; and to describe which symptoms are most limiting. This randomized control trial was conducted in two comprehensive and four community cancer centers. Two hundred thirty-seven individuals, aged 31-87, newly diagnosed with solid tumor cancers, participated. The experimental group (118 individuals) received a 10-contact, 18-week cognitive behavioral intervention focused on cancer- and chemotherapy-related symptoms. The control group (119 individuals) received conventional care. Interviews occurred at baseline, 10, 20, and 32 weeks. Data analysis used a two-level hierarchical linear model. Participants receiving the cognitive behavioral intervention had lower scores of symptom limitation than did participants in the control group. At the onset of the study, younger patients reported more symptom limitations than their older counterparts; however, this was reversed by the end of the study. The cognitive behavioral intervention was key to decreasing symptom limitations. Findings also suggest that nursing interventions may be particularly helpful to younger individuals in managing cancer-related symptom limitations. Copyright 2005 John Wiley & Sons, Ltd.

  1. Acupuncture for posttraumatic stress disorder: a randomized controlled pilot trial.

    PubMed

    Hollifield, Michael; Sinclair-Lian, Nityamo; Warner, Teddy D; Hammerschlag, Richard

    2007-06-01

    The purpose of the study was to evaluate the potential efficacy and acceptability of accupuncture for posttraumatic stress disorder (PTSD). People diagnosed with PTSD were randomized to either an empirically developed accupuncture treatment (ACU), a group cognitive-behavioral therapy (CBT), or a wait-list control (WLC). The primary outcome measure was self-reported PTSD symptoms at baseline, end treatment, and 3-month follow-up. Repeated measures MANOVA was used to detect predicted Group X Time effects in both intent-to-treat (ITT) and treatment completion models. Compared with the WLC condition in the ITT model, accupuncture provided large treatment effects for PTSD (F [1, 46] = 12.60; p < 0.01; Cohen's d = 1.29), similar in magnitude to group CBT (F [1, 47] = 12.45; p < 0.01; d = 1.42) (ACU vs. CBT, d = 0.29). Symptom reductions at end treatment were maintained at 3-month follow-up for both interventions. Accupuncture may be an efficacious and acceptable nonexposure treatment option for PTSD. Larger trials with additional controls and methods are warranted to replicate and extend these findings.

  2. Hypnosis for Smoking Relapse Prevention: A Randomized Trial.

    PubMed

    Carmody, Timothy P; Duncan, Carol L; Solkowitz, Sharon N; Huggins, Joy; Simon, Joel A

    2017-10-01

    The purpose of this study was to determine whether hypnosis would be more effective than standard behavioral counseling in helping smokers to remain abstinent. A total of 140 current smokers were enrolled in a randomized controlled smoking cessation trial at an urban Veterans Affairs medical center. Participants (n = 102) who were able to quit for at least 3 days received either a hypnosis or behavioral relapse prevention intervention. Both relapse prevention interventions consisted of two 60 min face-to-face sessions and four 20 min follow-up phone calls (two phone calls per week). At 26 weeks, the validate\\d point-prevalence quit rate was 35% for the hypnosis group and 42% for the behavioral counseling group (relative risk = 0.85; 95% confidence interval: 0.52-1.40). At 52 weeks, the validated quit rate was 29% for the hypnosis group and 28% for the behavioral group (relative risk  = 1.03; 95% confidence interval: 0.56-1.91). It was concluded that hypnosis warrants further investigation as an intervention for facilitating maintenance of quitting.

  3. Validating Obstetric Emergency Checklists using Simulation: A Randomized Controlled Trial.

    PubMed

    Bajaj, Komal; Rivera-Chiauzzi, Enid Y; Lee, Colleen; Shepard, Cynthia; Bernstein, Peter S; Moore-Murray, Tanya; Smith, Heather; Nathan, Lisa; Walker, Katie; Chazotte, Cynthia; Goffman, Dena

    2016-10-01

    Background The World Health Organization's Surgical Safety Checklist has demonstrated significant reduction in surgical morbidity. The American Congress of Obstetricians and Gynecologists District II Safe Motherhood Initiative (SMI) safety bundles include eclampsia and postpartum hemorrhage (PPH) checklists. Objective To determine whether use of the SMI checklists during simulated obstetric emergencies improved completion of critical actions and to elicit feedback to facilitate checklist revision. Study Design During this randomized controlled trial, teams were assigned to use a checklist during one of two emergencies: eclampsia and PPH. Raters scored teams on critical step completion. Feedback was elicited through structured debriefing. Results In total, 30 teams completed 60 scenarios. For eclampsia, trends toward higher completion were noted for blood pressure and airway management. For PPH, trends toward higher completion rates were noted for PPH stage assessment and fundal massage. Feedback resulted in substantial checklist revision. Participants were enthusiastic about using checklists in a clinical emergency. Conclusion Despite trends toward higher rates of completion of critical tasks, teams using checklists did not approach 100% task completion. Teams were interested in the application of checklists and provided feedback necessary to substantially revise the checklists. Intensive implementation planning and training in use of the revised checklists will result in improved patient outcomes.

  4. Effects of nattokinase on blood pressure: a randomized, controlled trial.

    PubMed

    Kim, Ji Young; Gum, Si Nae; Paik, Jean Kyung; Lim, Hyo Hee; Kim, Kyong-Chol; Ogasawara, Kazuya; Inoue, Kenichi; Park, Sungha; Jang, Yangsoo; Lee, Jong Ho

    2008-08-01

    The objective of this study was to examine the effects of nattokinase supplementation on blood pressure in subjects with pre-hypertension or stage 1 hypertension. In a randomized, double-blind, placebo-controlled trial, 86 participants ranging from 20 to 80 years of age with an initial untreated systolic blood pressure (SBP) of 130 to 159 mmHg received nattokinase (2,000 FU/capsule) or a placebo capsule for 8 weeks. Seventy-three subjects completed the protocol. Compared with the control group, the net changes in SBP and diastolic blood pressure (DBP) were -5.55 mmHg (95% confidence interval [CI], -10.5 to -0.57 mmHg; p<0.05) and -2.84 mmHg (CI, -5.33 to -0.33 mmHg; p<0.05), respectively, after the 8-week intervention. The corresponding net change in renin activity was -1.17 ng/mL/h for the nattokinase group compared with the control group (p<0.05). In conclusion, nattokinase supplementation resulted in a reduction in SBP and DBP. These findings suggest that increased intake of nattokinase may play an important role in preventing and treating hypertension.

  5. Randomized Trial of Clarithromycin for Mediterranean Spotted Fever

    PubMed Central

    Muñoz, Tomas; Travería, Francisco Javier; Navarro, Gemma; Font, Bernat; Sanfeliu, Isabel; Segura, Ferran

    2015-01-01

    The classic antibiotic treatment for Mediterranean spotted fever (MSF) is based on tetracyclines or chloramphenicol, but chloramphenicol's bone marrow toxicity makes tetracyclines the treatment of choice. However, it is convenient to have alternatives available for patients who are allergic to tetracyclines, pregnant women, and children <8 years old. We conducted a randomized clinical trial to compare clarithromycin with doxycycline or josamycin in the treatment of MSF. Forty patients were evaluated (23 male; mean age, 39.87 years); 13 patients were aged <14 years. Seventeen patients received clarithromycin, and 23 received doxycycline or josamycin. The interval between the onset of symptoms and the start of treatment was 4.04 ± 1.70 days in the clarithromycin group versus 4.11 ± 1.60 days in the doxycycline/josamycin group (P = not significant [NS]). Time to the disappearance of fever after treatment was 2.67 ± 1.55 days in the clarithromycin group versus 2.22 ± 1.35 days in the doxycycline/josamycin (P = NS). The symptoms had disappeared at 4.70 ± 2.25 days in the clarithromycin group versus at 4.75 ± 3.08 days in the doxycycline/josamycin (P = NS). There were no adverse reactions to treatment or relapses in either group. In conclusion, clarithromycin is a good alternative to doxycycline or josamycin in the treatment of MSF. PMID:26711765

  6. A multicentric, randomized clinical trial of Gaviscon in reflux esophagitis.

    PubMed

    McHardy, G

    1978-01-01

    Gaviscon tablets and the standard antacid proved equally effective in reducing the number of heartburn attacks. Chi-square tests revealed no significant difference between the two treatment groups at the end of weeks 1, 2, 3, or 4. Heartburn score was arrived at by multiplying heartburn incidence by heartburn severity. This heartburn score also indicated no significant difference between the two treatment groups at the end of the four weeks. Tabulation of the mean number of tablets consumed by patients in the two groups was made. There was no significant difference between the two groups in tablet consumption, indicating equal demand as well as equal compliance in the two groups. Esophagoscopy done before and after 28 days of treatment showed that Gaviscon and the standard antacid tablets were equally effective in each group. There was significant, and equal, decrease in the severity in the specific signs of esophagitis, friability, erosion, and ulceration in both treatment groups, as well as in such nonspecific signs as hyperemia, edema, and exudate. The validity and clinical acceptance of an alginic acid-containing agent, Gaviscon, which through a foaming action delivers a minimal dose of antacid directly at the site of acid irritation of the esophageal mucosa, has been confirmed in a multicentric, well-controlled randomized clinical trial.

  7. A mediator effect size in randomized clinical trials.

    PubMed

    Kraemer, Helena Chmura

    2014-12-01

    To understand the process by which a treatment (T) achieves an effect on outcome (O) and thus to improve the effect of T on O, it is vital to detect mediators, to compare the impact of different mediators, and to develop hypotheses about the causal factors (all mediators) linking T and O. An index is needed to facilitate interpretation of the potential clinical importance of a mediator (M) of choice of T on treatment O in randomized clinical trials (RCTs). Ideally such a mediator effect size should (1) be invariant under any rescaling of M and O consistent with the model used, and (2) reflect the difference between the overall observed effect of T on O and what the maximal effect of T on O could be were the association between T and M broken. A mediator effect size is derived first for the traditional linear model, and then more generally for any categorical (ordered or non-ordered) potential mediator. Issues such as the problem of multiple treatments, outcomes and mediators, and of causal inferences, and the correspondence between this approach and earlier ones, are discussed. Illustrations are given of the application of the approach. Copyright © 2014 John Wiley & Sons, Ltd.

  8. The design and analysis of randomized trials with recurrent events.

    PubMed

    Cook, R J

    1995-10-15

    This paper describes a method for planning the duration of a randomized parallel group study in which the response of interest is a potentially recurrent event. At the design stage we assume patients accrue at a constant rate, we model events via a homogeneous Poisson process, and we utilize an independent exponential censoring mechanism to reflect loss to follow-up. We derive the appropriate study duration to ensure satisfaction of power requirements for the effect size of interest under a Poisson regression model. An application to a kidney transplant study illustrates the potential savings of the Poisson-based design relative to a design based on the time to the first event. Revised design criteria are also derived to accommodate overdispersed Poisson count data. We examine the frequency properties of two non-parametric tests recently proposed by Lawless and Nadeau for trials based on the above design criteria. In simulation studies involving homogeneous and non-homogeneous Poisson processes they performed well with respect to their type I error rate and power. Results from supplementary simulation studies indicate that these tests are also robust to extra-Poisson variation and to clustering in the event times, making these tests attractive in their generality. We illustrate both tests by application to data from a completed kidney transplant study.

  9. Ameliorating children's reading-comprehension difficulties: a randomized controlled trial.

    PubMed

    Clarke, Paula J; Snowling, Margaret J; Truelove, Emma; Hulme, Charles

    2010-08-01

    Children with specific reading-comprehension difficulties can read accurately, but they have poor comprehension. In a randomized controlled trial, we examined the efficacy of three interventions designed to improve such children's reading comprehension: text-comprehension (TC) training, oral-language (OL) training, and TC and OL training combined (COM). Children were assessed preintervention, midintervention, postintervention, and at an 11-month follow-up. All intervention groups made significant improvements in reading comprehension relative to an untreated control group. Although these gains were maintained at follow-up in the TC and COM groups, the OL group made greater gains than the other groups did between the end of the intervention and follow-up. The OL and COM groups also demonstrated significant improvements in expressive vocabulary compared with the control group, and this was a mediator of the improved reading comprehension of the OL and COM groups. We conclude that specific reading-comprehension difficulties reflect (at least partly) underlying oral-language weaknesses that can be effectively ameliorated by suitable teaching.

  10. A randomized trial of calorie labeling on menus.

    PubMed

    Hammond, David; Goodman, Samantha; Hanning, Rhona; Daniel, Samantha

    2013-12-01

    Food consumed outside the home accounts for a growing proportion of the North American diet and has been associated with increased obesity. To examine the effect of nutrition labeling on menus on awareness, use, and food consumption, including the impact of "traffic light" labeling and adding other nutrients. Blinded, randomized trial with 635 Canadian adults conducted in 2010-2011. Participants ordered a free meal from one of four experimental menus: 1) no nutritional information shown, 2) calorie amounts only, 3) calorie amounts in "traffic lights", and 4) calorie, fat, sodium, and sugar shown in "traffic lights". Recall of nutrition information, knowledge of calorie content and nutrient consumption were assessed. Participants in the calorie conditions were more likely to recall the calorie content of meals and to report using nutrition information when ordering. The calorie content of meals was not significantly different across conditions; however, calorie consumption was significantly lower among participants in the Calorie-only condition compared to the No information condition (mean=-96 kcal, p=.048). Menu labeling increased awareness and use of nutrition information and reduced consumption. Adding "traffic lights", fat, sodium, and sugar amounts to menus had little impact compared to calorie-only labeling. © 2013.

  11. Reducing mucus production after urinary reconstruction: a prospective randomized trial.

    PubMed

    N'Dow, J; Robson, C N; Matthews, J N; Neal, D E; Pearson, J P

    2001-05-01

    After transposition into the urinary tract, intestinal segments continue to produce mucus. We determine the effectiveness of muco-regulatory drugs, including N-acetylcysteine, aspirin and ranitidine, in reducing mucus secretion and urine viscosity in patients with transposed segments. Our trial was a prospective randomized, double-blind placebo controlled crossover study involving 12 patients who underwent ileal conduit and 31 who underwent bladder reconstruction. Each treatment lasted 3 weeks with a 2-week washout. Pretreatment and posttreatment 24-hour urine samples were analyzed for mucin and viscosity after papain digestion, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and periodic acid-Schiff assay. A disease specific questionnaire and SF-36 quality of life survey were completed. According to the questionnaire, mucus production did not decrease with time in 67% of patients. Mucin comprised 3% of the total nondialyzable material in urine (65 mg./24-hour for ileal conduit and 60 mg./24-hour for bladder reconstruction). Analysis of questionnaires and laboratory results failed to demonstrate any benefit of taking muco-regulatory agents compared with placebo. The use of N-acetylcysteine, aspirin and ranitidine did not result in a reduction in mucin production, urine viscosity or improvement in quality of life.

  12. Randomized controlled trial of ionization and photoelectric smoke alarm functionality.

    PubMed

    Mueller, B A; Sidman, E A; Alter, H; Perkins, R; Grossman, D C

    2008-04-01

    To compare functionality, reasons for non-function, and nuisance alarm levels of two common types of smoke alarms after installation in low- to mid-level income households in King County, Washington. Randomized controlled trial of 761 households. An ionization or photoelectric smoke alarm was installed between June 1, 2000 and July 31, 2002. Main outcome measures were: percentage of study alarms that were working, observed reasons for non-functional status, and self-reported frequency of nuisance alarms at 9 and 15 months of follow-up. At 9 months after installation, 20% of ionization, vs 5% of photoelectric alarms were non-functional, a difference that persisted at 15 months, with the most common reasons for both types being a disconnected or absent battery. The risk ratio for ionization, relative to photoelectric alarms, being non-functional or removed was 2.7 (95% CI 1.8 to 4.1) at 15 months of follow-up. These findings were not altered by educational level, or the presence of smokers, children <5 years, or adults > or =65 years. Burn prevention efforts are geared towards increasing smoke alarm ownership and improving maintenance of functional status. Results suggest that the selective use of photoelectric alarms by fire injury prevention programs or consumers may provide longer-term protection in similar populations. Designing smoke alarms that minimize nuisance alarming may also result in longer term functionality.

  13. Randomized clinical trial of topical tranexamic acid after reduction mammoplasty

    PubMed Central

    Ausen, K; Fossmark, R; Spigset, O; Pleym, H

    2015-01-01

    Background The antifibrinolytic drug tranexamic acid is currently being rediscovered for both trauma and major surgery. Intravenous administration reduces the need for blood transfusion and blood loss by about one-third, but routine administration in surgery is not yet advocated owing to concerns regarding thromboembolic events. The aim of this study was to investigate whether topical application of tranexamic acid to a wound surface reduces postoperative bleeding. Methods This was a randomized double-blind placebo-controlled trial on 30 consecutive women undergoing bilateral reduction mammoplasty. On one side the wound surfaces were moistened with 25 mg/ml tranexamic acid before closure, and placebo (saline) was used on the other side. Drain fluid production was measured for 24 h after surgery, and pain was measured after 3 and 24 h. Postoperative complications including infection, seroma, rebleeding and suture reactions were recorded. Results Topical application of tranexamic acid to the wound surface after reduction mammoplasty reduced drain fluid production by 39 per cent (median 12·5 (range 0–44) versus 20·5 (0–100) ml; P = 0·038). Adverse effects were not observed. There were no significant differences in postoperative pain scores or complications. Conclusion Topical application of dilute tranexamic acid reduced bleeding in this model. The study adds to the evidence that this simple procedure may reduce wound bleeding after surgery. Registration number: NCT01964781 (http://www.clinicaltrials.gov). PMID:26349843

  14. Physicians promoting bicycle helmets for children: a randomized trial.

    PubMed Central

    Cushman, R; James, W; Waclawik, H

    1991-01-01

    Head injury is the leading cause of death and serious morbidity in bicycle accidents. There is good evidence to recommend helmets, yet few children wear them. We evaluated helmet promotion in a randomized trial targeting children presenting to primary care settings for routine ambulatory care. The intervention consisted of physician counseling and take-home pamphlets. The study involved 339 families, 167 in the intervention group and 172 in the control group. In a follow-up telephone call, 2 to 3 weeks later, only 7.2% of the intervention group had purchased helmets, compared with 7.0% of the control group (chi 2 = 0.0056, P = .94). During the latter half of the study, bicycle safety received considerable media attention in Ottawa, and the provincial medical society sponsored a $5 discount campaign. Therefore both groups were subject to community "co-intervention." Nonetheless, we were surprised that physician counseling made no additional impact. Our results and the success of certain community programs suggest that physicians interested in helmet promotion would do better to participate in the design and implementation of multidisciplinary campaigns. PMID:1853997

  15. Evaluating cognitive effort in a randomized controlled trial.

    PubMed

    Turner, Travis H; Renfroe, Jenna B; Morella, Kristen; Marriott, Bernadette P

    2016-09-01

    Many randomized controlled trials (RCTs) of neuropsychiatric conditions involve cognitive outcome measures; however, validity of cognitive data relies on adequate effort during testing, and such screening is seldom performed. Given well-established rates of 10 to 30% poor effort in clinical settings, this is not a trivial concern. This preliminary study evaluated effort during cognitive testing in an RCT of omega-3 supplementation to reduce suicidality in a high-risk psychiatric population. An interim analysis of sustained attentions measures from the Connors Performance Test (CPT-2) at baseline for the first 60 participants was conducted. Previously validated cut points to detect insufficient effort on the CPT-2 were applied. At baseline, 12% (7) were identified as giving poor effort. Follow-up analyses indicated less psychiatric distress and suicidality among those who gave poor effort. Results suggest comparable likelihood of a poor effort on cognitive testing in clinical and RCT participation. Reduced psychiatric distress in the poor effort group raises concern regarding interpretation of other measures. The importance of screening cognitive data for effort in RCTs is highlighted. Future studies will examine effort at follow-up visits, and explore relationships to attrition, adherence, and response to treatment. Copyright © 2016 John Wiley & Sons, Ltd.

  16. A randomized trial of dietary sodium restriction in CKD.

    PubMed

    McMahon, Emma J; Bauer, Judith D; Hawley, Carmel M; Isbel, Nicole M; Stowasser, Michael; Johnson, David W; Campbell, Katrina L

    2013-12-01

    There is a paucity of quality evidence regarding the effects of sodium restriction in patients with CKD, particularly in patients with pre-end stage CKD, where controlling modifiable risk factors may be especially important for delaying CKD progression and cardiovascular events. We conducted a double-blind placebo-controlled randomized crossover trial assessing the effects of high versus low sodium intake on ambulatory BP, 24-hour protein and albumin excretion, fluid status (body composition monitor), renin and aldosterone levels, and arterial stiffness (pulse wave velocity and augmentation index) in 20 adult patients with hypertensive stage 3-4 CKD as phase 1 of the LowSALT CKD study. Overall, salt restriction resulted in statistically significant and clinically important reductions in BP (mean reduction of systolic/diastolic BP, 10/4 mm Hg; 95% confidence interval, 5 to 15 /1 to 6 mm Hg), extracellular fluid volume, albuminuria, and proteinuria in patients with moderate-to-severe CKD. The magnitude of change was more pronounced than the magnitude reported in patients without CKD, suggesting that patients with CKD are particularly salt sensitive. Although studies with longer intervention times and larger sample sizes are needed to confirm these benefits, this study indicates that sodium restriction should be emphasized in the management of patients with CKD as a means to reduce cardiovascular risk and risk for CKD progression.

  17. Fundamentals of randomized clinical trials in wound care: reporting standards.

    PubMed

    Brölmann, Fleur E; Eskes, Anne M; Sumpio, Bauer E; Mayer, Dieter O; Moore, Zena; Agren, Magnus S; Hermans, Michel; Cutting, Keith; Legemate, Dink A; Vermeulen, Hester; Ubbink, Dirk T

    2013-01-01

    In wound care research, available high-level evidence according to the evidence pyramid is rare, and is threatened by a poor study design and reporting. Without comprehensive and transparent reporting, readers will not be able to assess the strengths and limitations of the research performed. Randomized clinical trials (RCTs) are universally acknowledged as the study design of choice for comparing treatment effects. To give high-level evidence the appreciation it deserves in wound care, we propose a step-by-step reporting standard for comprehensive and transparent reporting of RCTs in wound care. Critical reporting issues (e.g., wound care terminology, blinding, predefined outcome measures, and a priori sample size calculation) and wound-specific barriers (e.g., large diversity of etiologies and comorbidities of patients with wounds) that may prevent uniform implementation of reporting standards in wound care research are addressed in this article. The proposed reporting standards can be used as guidance for authors who write their RCT, as well as for peer reviewers of journals. Endorsement and application of these reporting standards may help achieve a higher standard of evidence and allow meta-analysis of reported wound care data. The ultimate goal is to help wound care professionals make better decisions for their patients in clinical practice. © 2013 by the Wound Healing Society.

  18. Breast screening with mammography: Overview of Swedish randomized trials

    SciTech Connect

    Nystroem, L.; Wall, S. . Dept. of Epidemiology and Public Health); Rutqvist, L.E. . Oncologic Centre); Lindgren, A. ); Lindqvist, M. ); Ryden, S. ); Andersson, J. ); Bjurstam, N. ); Fagerberg, G. ); Frisell, J. ); Tabar, L. ); Larson, L.G. . Oncologic Centre)

    1993-04-17

    Despite encouraging results from screening trials the efficacy of mammography in reducing mortality remains somewhat controversial. Five studies have been done in Sweden. This overview, reveals a 24% significant reduction of breast cancer mortality among those invited to mammography screening compared with those not invited. To avoid the potential risk of differential misclassification causes of death were assessed by an independent end-point committee after a blinded review of all fatal breast cancer cases. The mortality reduction was similar, irrespective of the end-point used for evaluation (breast cancer as underlying cause of death or breast cancer present at death). There was a consistent risk reduction associated with screening in all studies, although the point estimate of the relative risk for all ages varied non-significantly between 0.68 and 0.84. The cumulative breast cancer mortality by time since randomization was estimated at 1.3 per 1,000 within 6 years in the invited group compared with 1.6 in the control group. The corresponding figures after 9 years are 2.6 and 3.3 and after 12 years 3.9 and 5.1.

  19. Improving residents' code status discussion skills: a randomized trial.

    PubMed

    Szmuilowicz, Eytan; Neely, Kathy J; Sharma, Rashmi K; Cohen, Elaine R; McGaghie, William C; Wayne, Diane B

    2012-07-01

    Inpatient Code Status Discussions (CSDs) are commonly facilitated by resident physicians, despite inadequate training. We studied the efficacy of a CSD communication skills training intervention for internal medicine residents. This was a prospective, randomized controlled trial of a multimodality communication skills educational intervention for postgraduate year (PGY) 1 residents. Intervention group residents completed a 2 hour teaching session with deliberate practice of communication skills, online modules, self-reflection, and a booster training session in addition to assigned clinical rotations. Control group residents completed clinical rotations alone. CSD skills of residents in both groups were assessed 2 months after the intervention using an 18 item behavioral checklist during a standardized patient encounter. Average scores for intervention and control group residents were calculated and between-group differences on the CSD skills assessment were evaluated using two-tailed independent sample t tests. Intervention group residents displayed higher overall scores on the simulated CSD (75.1% versus 53.2%, p<0.0001) than control group residents. The intervention group also displayed a greater number of key CSD communication behaviors and facilitated significantly longer conversations. The training, evaluation, and feedback sessions were rated highly. A focused, multimodality curriculum can improve resident performance of simulated CSDs. Skill improvement lasted for at least 2 months after the intervention. Further studies are needed to assess skill retention and to set minimum performance standards.

  20. Biofeedback treatment for Tourette syndrome: a preliminary randomized controlled trial.

    PubMed

    Nagai, Yoko; Cavanna, Andrea E; Critchley, Hugo D; Stern, Jeremy J; Robertson, Mary M; Joyce, Eileen M

    2014-03-01

    To study the clinical effectiveness of biofeedback treatment in reducing tics in patients with Tourette syndrome. Despite advances in the pharmacologic treatment of patients with Tourette syndrome, many remain troubled by their tics, which may be resistant to multiple medications at tolerable doses. Electrodermal biofeedback is a noninvasive biobehavioral intervention that can be useful in managing neuropsychiatric and neurologic conditions. We conducted a randomized controlled trial of electrodermal biofeedback training in 21 patients with Tourette syndrome. After training the patients for 3 sessions a week over 4 weeks, we observed a significant reduction in tic frequency and improved indices of subjective well-being in both the active-biofeedback and sham-feedback (control) groups, but there was no difference between the groups in these measurements. Furthermore, the active-treatment group did not demonstrably learn to reduce their sympathetic electrodermal tone using biofeedback. Our findings indicate that this form of biofeedback training was unable to produce a clinical effect greater than placebo. The main confounding factor appeared to be the 30-minute duration of the training sessions, which made it difficult for patients to sustain a reduction in sympathetic tone when their tics themselves were generating competing phasic electrodermal arousal responses. Despite a negative finding in this study, electrodermal biofeedback training may have a role in managing tics if optimal training schedules can be identified.

  1. [Pain prevention in term neonates: randomized trial for three methods].

    PubMed

    Bonetto, Germán; Salvatico, Estela; Varela, Natalia; Cometto, Cristina; Gómez, Patricia F; Calvo, Bernardo

    2008-10-01

    Every newborn infant is screened for hypothyroidism and phenylketonuria by blood sampling, during the first week of life, but there is not a simple and efficient method to reduce pain during the procedure. Prospective randomised trial, to assess if the administration of oral glucose, paracetamol or EMLA, given individually, can reduce the pain caused in newborns by heel prick, in an outpatient setting. Double-blind study in which seventy six healthy newborns at term were randomly assigned to receive placebo, oral glucose, EMLA in the heel, or oral paracetamol. Heel prick was performed to get a blood sample, and pain was measured by two independent observers, using two scales (NIPS and PIPP). NIPS <4: placebo (9/19= 47%), glucose (16/19= 84%), paracetamol (8/19= 42%) and EMLA (12/19= 63%); PIPP <8: placebo (9/19= 47%), oral glucose (12/19= 63%), paracetamol (5/19= 26%) and EMLA (8/19= 42%). With the use of oral glucose we found RAR: 0.37 (IC 95% 0.09-0.64), RRR: 44% (IC 95% 6-67%), NNT: 2.7 (IC 95% 1.5-11). The best results were obtained with the use of oral glucose, being statistically significant with only one of the scales. The administration of paracetamol or EMLA did not reduce pain. Other complementary and/or combined methods, added to oral glucose, should be considered daily to diminish this painful experience in thousands of children.

  2. Tacrolimus monotherapy in membranous nephropathy: a randomized controlled trial.

    PubMed

    Praga, M; Barrio, V; Juárez, G Fernández; Luño, J

    2007-05-01

    Membranous nephropathy is a common cause of nephrotic syndrome in adults. Although some patients with membranous nephropathy achieve a spontaneous remission, renal function continues to deteriorate in others. We conducted a prospective randomized trial evaluating monotherapy with tacrolimus to achieve complete or partial remission in patients with biopsy-proven membranous nephropathy. Twenty-five patients received tacrolimus (0.05 mg/kg/day) over 12 months with a 6-month taper, whereas 23 patients were in the control group. The probability of remission in the treatment group was 58, 82, and 94% after 6, 12, and 18 months but only 10, 24, and 35%, respectively in the control group. The decrease in proteinuria was significantly greater in the treatment group. Notably, six patients in the control group and only one in the treatment group reached the secondary end point of a 50% increase in their serum creatinine. No patient in the tacrolimus group showed a relapse during the taper period. Nephrotic syndrome reappeared in almost half of the patients who were in remission by the 18th month after tacrolimus withdrawal. We conclude that tacrolimus is a very useful therapeutic option for patients with membranous nephropathy and preserved renal function. The majority of patients experienced remission with a significant reduction in the risk for deteriorating renal function.

  3. Randomized clinical trial of peganum oil for knee osteoarthritis.

    PubMed

    Abolhassanzadeh, Zohreh; Aflaki, Elham; Yousefi, Gholamhossein; Mohagheghzadeh, Abdolali

    2015-04-01

    Osteoarthritis affects about 50% of people aged older than 65 years. Pain is the most important symptom in this disease. Today public interest in the use of complementary medicine, especially traditional herbal medicines has increased. The present study was designed to investigate the efficacy of traditional preparation of Peganum harmala L oil on patients with knee osteoarthritis. The product has been analyzed and standardized by high-performance liquid chromatography. A double blind controlled randomized clinical trial consisting of 54 patients were performed. Patients rubbed the drug or control (olive oil) on the knee 4 drops 3 times a day for 4 weeks. The patients were asked to fill out the Western Ontario and McMaster Universities Arthritis Index and Visual Analogue Scale questionnaires at week 0 and 4. The adapted results from the questionnaires showed that pain and difficulty in function were significantly decreased in Peganum oil group after 4 weeks. There was no significant difference in stiffness change between 2 groups.

  4. Sexual assault resistance education for university women: study protocol for a randomized controlled trial (SARE trial)

    PubMed Central

    2013-01-01

    Background More than one in six women will be sexually assaulted in their lifetimes, most by men they know. The situation on university campuses is even more startling, with as many as 1 in 4 female students being victims of rape or attempted rape. The associated physical and mental health effects are extensive and the social and economic costs are staggering. The aim of this randomized controlled trial is to determine whether a novel, small-group sexual assault resistance education program can reduce the incidence of sexual assault among university-attending women, when compared to current university practice of providing informational brochures. Methods/Design The trial will evaluate a theoretically and empirically sound four-unit, 12-hour education program that has been demonstrated in pilot studies to have short-term efficacy. Three of the four units provide information, skills, and practice aimed at decreasing the time needed for women to assess situations with elevated risk of acquaintance sexual assault as dangerous and to take action, reducing emotional obstacles to taking action, and increasing the use of the most effective methods of verbal and physical self-defense. The fourth unit focuses on facilitating a stronger positive sexuality from which women may resist sexual coercion by male intimates more successfully. The trial will extend the pilot evaluations by expanding the participant pool and examining the long term efficacy of the program. A total of 1716 first-year female students (age 17 to 24 years) from three Canadian universities will be enrolled. The primary outcome is completed sexual assault, measured by The Sexual Experiences Survey - Short Form Victimization instrument. Secondary outcomes include changes in knowledge, attitudes, and skills related to the process of sexual assault resistance. Outcomes will be measured at baseline, 1 week, 6, 12, 18, and 24 months. Discussion The results of the trial will be used to produce a maximally

  5. Simulation of various randomization strategies for a clinical trial in sickle cell disease.

    PubMed

    Meurer, William J; Connor, Jason T; Glassberg, Jeffrey

    2016-05-01

    To use numerical simulation to evaluate various randomization strategies for a clinical trial in sickle cell disease (SCD). The Inhaled Mometasone to Promote Reduction in Vaso-occlusive Events trial* is a randomized, controlled, feasibility study of inhaled mometasone for individuals with SCD who do not have asthma. The target sample size is 45 patients and one goal is to limit imbalance with respect to two important covariates (1) hydroxyurea use and (2) historical emergency department (ED) utilization. We compared three methods of patient allocation (simple randomization, block randomization, and biased-coin adaptive randomization) using numerical simulation (10 000 trials). The primary outcome measure was the proportion of simulated trials with numerically apparent differences in the two covariates: hydroxyurea use (binary) and ED utilization (three-level ordinal). Overall, only 1.6% of simulated trials had any covariate comparison with P < 0.3 across groups for simple randomization, and 0% for both the block and adaptive randomization. In trials where the total sample size was 45 patients, the block randomization strategy achieved the greatest balance because participants were deterministically assigned to the treatment arm that balanced covariates. The adaptive strategy achieved similar results without deterministic treatment assignments even when trials included only 45 patients. Adaptive clinical trial designs have potential to mitigate some of the challenges that have hampered SCD trials. In small exploratory trials, even non-statistically significant differences in important covariates can threaten interpretability and external validity. Adaptive randomization performed similarly to block randomization and offers advantages including better allocation concealment and less ability for investigators to predict the next assignment.

  6. Meditation for migraines: a pilot randomized controlled trial.

    PubMed

    Wells, Rebecca Erwin; Burch, Rebecca; Paulsen, Randall H; Wayne, Peter M; Houle, Timothy T; Loder, Elizabeth

    2014-10-01

    Our objective was to assess the safety, feasibility, and effects of the standardized 8-week mindfulness-based stress reduction (MBSR) course in adults with migraines. Stress is a well-known trigger for headaches. Research supports the general benefits of mind/body interventions for migraines, but there are few rigorous studies supporting the use of specific standardized interventions. MBSR is a standardized 8-week mind/body intervention that teaches mindfulness meditation/yoga. Preliminary research has shown MBSR to be effective for chronic pain syndromes, but it has not been evaluated for migraines. We conducted a randomized controlled trial with 19 episodic migraineurs randomized to either MBSR (n = 10) or usual care (n = 9). Our primary outcome was change in migraine frequency from baseline to initial follow-up. Secondary outcomes included change in headache severity, duration, self-efficacy, perceived stress, migraine-related disability/impact, anxiety, depression, mindfulness, and quality of life from baseline to initial follow-up. MBSR was safe (no adverse events), with 0% dropout and excellent adherence (daily meditation average: 34 ± 11 minutes, range 16-50 minutes/day). Median class attendance from 9 classes (including retreat day) was 8 (range [3, 9]); average class attendance was 6.7 ± 2.5. MBSR participants had 1.4 fewer migraines/month (MBSR: 3.5 to 1.0 vs control: 1.2 to 0 migraines/month, 95% confidence interval CI [-4.6, 1.8], P = .38), an effect that did not reach statistical significance in this pilot sample. Headaches were less severe, although not significantly so (-1.3 points/headache on 0-10 scale, [-2.3, 0.09], P = .053) and shorter (-2.9 hours/headache, [-4.6, -0.02], P = .043) vs control. Migraine Disability Assessment and Headache Impact Test-6 dropped in MBSR vs control (-12.6, [-22.0, -1.0], P = .017 and -4.8, [-11.0, -1.0], P = .043, respectively). Self-efficacy and mindfulness improved in MBSR vs control (13.2 [1.0, 30.0], P

  7. A comparison of handsearching versus MEDLINE searching to identify reports of randomized controlled trials.

    PubMed

    Hopewell, S; Clarke, M; Lusher, A; Lefebvre, C; Westby, M

    2002-06-15

    This study aims to compare handsearching to a basic MEDLINE search for the identification of reports of randomized trials in specialized health care journals. Twenty-two specialized health care journals, published in the U.K., were handsearched for all reports of controlled trials (as defined by the Cochrane Collaboration). The reports of trials, which were judged to be definitely randomized, were identified from a random sample of three years per journal and form one element of this study. A MEDLINE search using the publication type terms 'randomized controlled trial' and 'controlled clinical trial' was also performed for the same journal years. The reports of trials retrieved by handsearching were then compared against those retrieved from the MEDLINE search, to identify differences in retrieval between the two techniques. Reports of randomized trials identified by the MEDLINE search but not found by handsearching were individually assessed to see if they met the Cochrane eligibility criteria for a report of a randomized trial. A total of 714 reports of randomized trials were found by using a combination of both handsearching and MEDLINE searching. Of these, 369 (52 per cent) were identified only by handsearching and 32 (4 per cent) were identified only by MEDLINE searching. Of the reports identified only by handsearching, 252 had no MEDLINE record, of which 232 (92 per cent) were meeting abstracts or published in supplements; 117 (25 per cent) of the 462 reports of randomized trials which had a MEDLINE record were missed by the electronic search because they did not have either of the publication type terms 'randomized controlled trial' or 'controlled clinical trial'. This proportion varied depending on when the reports of randomized trials were published (that is, before or after the introduction of the MEDLINE publication type terms above). The highest additional yield from handsearching compared to MEDLINE searching was for reports of randomized trials

  8. The HAART cell phone adherence trial (WelTel Kenya1): a randomized controlled trial protocol.

    PubMed

    Lester, Richard T; Mills, Edward J; Kariri, Antony; Ritvo, Paul; Chung, Michael; Jack, William; Habyarimana, James; Karanja, Sarah; Barasa, Samson; Nguti, Rosemary; Estambale, Benson; Ngugi, Elizabeth; Ball, T Blake; Thabane, Lehana; Kimani, Joshua; Gelmon, Lawrence; Ackers, Marta; Plummer, Francis A

    2009-09-22

    The objectives are to compare the effectiveness of cell phone-supported SMS messaging to standard care on adherence, quality of life, retention, and mortality in a population receiving antiretroviral therapy (ART) in Nairobi, Kenya. A multi-site randomized controlled open-label trial. A central randomization centre provided opaque envelopes to allocate treatments. Patients initiating ART at three comprehensive care clinics in Kenya will be randomized to receive either a structured weekly SMS ('short message system' or text message) slogan (the intervention) or current standard of care support mechanisms alone (the control). Our hypothesis is that using a structured mobile phone protocol to keep in touch with patients will improve adherence to ART and other patient outcomes. Participants are evaluated at baseline, and then at six and twelve months after initiating ART. The care providers keep a weekly study log of all phone based communications with study participants. Primary outcomes are self-reported adherence to ART and suppression of HIV viral load at twelve months scheduled follow-up. Secondary outcomes are improvements in health, quality of life, social and economic factors, and retention on ART. Primary analysis is by 'intention-to-treat'. Sensitivity analysis will be used to assess per-protocol effects. Analysis of covariates will be undertaken to determine factors that contribute or deter from expected and determined outcomes. This study protocol tests whether a novel structured mobile phone intervention can positively contribute to ART management in a resource-limited setting.

  9. Acupressure Therapy for Acute Ankle Sprains: A Randomized Clinical Trial.

    PubMed

    Zhao, Mingxing; Gao, Wei; Zhang, Long; Huang, Wei; Zheng, Sihua; Wang, Guanliang; Hong, Brian Y; Tang, Baoyong

    2017-06-19

    Ankle sprains occur frequently among young and active people, accounting for almost 2 million injuries per year. Previous reports suggest that acupressure therapy for acute ankle sprains may shorten the recovery time. To evaluate whether acupressure therapy can improve ankle sprain recovery compared with standard RICE (rest, ice, compression, and elevation) treatment. A randomized controlled trial was conducted. The study protocol was registered in the Chinese Clinical Trial Registry with the study registration number: ChiCTR-TRC-14004794. Department of Traditional Chinese Medicine Orthopedics, PLA No.60 Center Hospital, Dali, China, and Department of Orthopedics, Xixi Hospital of Hangzhou, Hangzhou China, between June 2014 and January 2016. A total of 68 patients with acute ankle sprains were assessed for study eligibility, and a total of 62 patients were included in the present study. All patients with ankle sprains seen by the Orthopedics Department within 48 hours since the time of injury were identified. Consenting patients were randomized to either (1) standard treatment (ST group), (2) standard treatment + acupressure (AP group), or (3) standard treatment + mock acupressure (mock AP group). Outcomes of interest included a volumetric measurement of the foot, ankle, and lower leg), range of ankle movement, and visual analog pain scores. The American Orthopedic Foot and Ankle Score) and SF12v2 scores were used to assess quality of life. Among the 62 randomized patients, the mean (95% confidence interval [CI]) volumetric measurement of the foot, ankle, and lower leg in the AP group decreased from 185.24 (95% CI 142.80-227.67) to 62.14 (95% CI 44.03-80.25) after 3 sessions of acupressure treatment. This was a statistically significant difference (P < .01) compared with the means of ST group (119.00; 95% CI 89.14-148.86) and mock AP group (118.18; 95% CI 83.99-152.37). After the first treatment, the mean range of ankle movement, visual analog pain scores, and

  10. An easily accessible Web-based minimization random allocation system for clinical trials.

    PubMed

    Xiao, Lan; Huang, Qiwen; Yank, Veronica; Ma, Jun

    2013-07-19

    Minimization as an adaptive allocation technique has been recommended in the literature for use in randomized clinical trials. However, it remains uncommonly used due in part to a lack of easily accessible implementation tools. To provide clinical trialists with a robust, flexible, and readily accessible tool for implementing covariate-adaptive biased-coin randomization. We developed a Web-based random allocation system, MinimRan, that applies Pocock-Simon (for trials with 2 or more arms) and 2-way (currently limited to 2-arm trials) minimization methods for trials using only categorical prognostic factors or the symmetric Kullback-Leibler divergence minimization method for trials (currently limited to 2-arm trials) using continuous prognostic factors with or without categorical factors, in covariate-adaptive biased-coin randomization. In this paper, we describe the system's essential statistical and computer programming features and provide as an example the randomization results generated by it in a recently completed trial. The system can be used in single- and double-blind trials as well as single-center and multicenter trials. We expect the system to facilitate the translation of the 3 validated random allocation methods into broad, efficient clinical research practice.

  11. An Easily Accessible Web-Based Minimization Random Allocation System for Clinical Trials

    PubMed Central

    Xiao, Lan; Huang, Qiwen; Yank, Veronica

    2013-01-01

    Background Minimization as an adaptive allocation technique has been recommended in the literature for use in randomized clinical trials. However, it remains uncommonly used due in part to a lack of easily accessible implementation tools. Objective To provide clinical trialists with a robust, flexible, and readily accessible tool for implementing covariate-adaptive biased-coin randomization. Methods We developed a Web-based random allocation system, MinimRan, that applies Pocock–Simon (for trials with 2 or more arms) and 2-way (currently limited to 2-arm trials) minimization methods for trials using only categorical prognostic factors or the symmetric Kullback–Leibler divergence minimization method for trials (currently limited to 2-arm trials) using continuous prognostic factors with or without categorical factors, in covariate-adaptive biased-coin randomization. Results In this paper, we describe the system’s essential statistical and computer programming features and provide as an example the randomization results generated by it in a recently completed trial. The system can be used in single- and double-blind trials as well as single-center and multicenter trials. Conclusions We expect the system to facilitate the translation of the 3 validated random allocation methods into broad, efficient clinical research practice. PMID:23872035

  12. Estimation of treatment efficacy with complier average causal effects (CACE) in a randomized stepped wedge trial.

    PubMed

    Gruber, Joshua S; Arnold, Benjamin F; Reygadas, Fermin; Hubbard, Alan E; Colford, John M

    2014-05-01

    Complier average causal effects (CACE) estimate the impact of an intervention among treatment compliers in randomized trials. Methods used to estimate CACE have been outlined for parallel-arm trials (e.g., using an instrumental variables (IV) estimator) but not for other randomized study designs. Here, we propose a method for estimating CACE in randomized stepped wedge trials, where experimental units cross over from control conditions to intervention conditions in a randomized sequence. We illustrate the approach with a cluster-randomized drinking water trial conducted in rural Mexico from 2009 to 2011. Additionally, we evaluated the plausibility of assumptions required to estimate CACE using the IV approach, which are testable in stepped wedge trials but not in parallel-arm trials. We observed small increases in the magnitude of CACE risk differences compared with intention-to-treat estimates for drinking water contamination (risk difference (RD) = -22% (95% confidence interval (CI): -33, -11) vs. RD = -19% (95% CI: -26, -12)) and diarrhea (RD = -0.8% (95% CI: -2.1, 0.4) vs. RD = -0.1% (95% CI: -1.1, 0.9)). Assumptions required for IV analysis were probably violated. Stepped wedge trials allow investigators to estimate CACE with an approach that avoids the stronger assumptions required for CACE estimation in parallel-arm trials. Inclusion of CACE estimates in stepped wedge trials with imperfect compliance could enhance reporting and interpretation of the results of such trials.

  13. Sweet Sixteen: The Prospective Clinical Trials of John L. Cameron, MD-The Clinician-Scientist: From Alternate-Allocation to Randomized Controlled Trials.

    PubMed

    Yeo, Charles J

    2017-09-15

    : The era of randomized controlled trials was ushered in by the British epidemiologist-statistician Austin Bradford Hill, with his work on the use of streptomycin in patients with tuberculosis. John L. Cameron, can be linked to 16 prospective clinical trials over his career thus far, starting with alternate-allocation trials and transitioning to prospective, randomized, placebo-controlled trials. These trials studied various topics in surgery-from pancreatitis to surgical site infections, to drain trials, a trial in Crohn disease and multiple trials in pancreatic surgery and cancer. Herein are described the "sweet sixteen" prospective clinical trials of Dr Cameron.

  14. Randomized Trial of Benznidazole for Chronic Chagas' Cardiomyopathy.

    PubMed

    Morillo, Carlos A; Marin-Neto, Jose Antonio; Avezum, Alvaro; Sosa-Estani, Sergio; Rassi, Anis; Rosas, Fernando; Villena, Erick; Quiroz, Roberto; Bonilla, Rina; Britto, Constança; Guhl, Felipe; Velazquez, Elsa; Bonilla, Laura; Meeks, Brandi; Rao-Melacini, Purnima; Pogue, Janice; Mattos, Antonio; Lazdins, Janis; Rassi, Anis; Connolly, Stuart J; Yusuf, Salim

    2015-10-01

    The role of trypanocidal therapy in patients with established Chagas' cardiomyopathy is unproven. We conducted a prospective, multicenter, randomized study involving 2854 patients with Chagas' cardiomyopathy who received benznidazole or placebo for up to 80 days and were followed for a mean of 5.4 years. The primary outcome in the time-to-event analysis was the first event of any of the components of the composite outcome of death, resuscitated cardiac arrest, sustained ventricular tachycardia, insertion of a pacemaker or implantable cardioverter-defibrillator, cardiac transplantation, new heart failure, stroke, or other thromboembolic event. The primary outcome occurred in 394 patients (27.5%) in the benznidazole group and in 414 (29.1%) in the placebo group (hazard ratio, 0.93; 95% confidence interval [CI], 0.81 to 1.07; P=0.31). At baseline, a polymerase-chain-reaction (PCR) assay was performed on blood samples obtained from 1896 patients; 60.5% had positive results for Trypanosoma cruzi on PCR. The rates of conversion to negative PCR results (PCR conversion) were 66.2% in the benznidazole group and 33.5% in the placebo group at the end of treatment, 55.4% and 35.3%, respectively, at 2 years, and 46.7% and 33.1%, respectively, at 5 years or more (P<0.001 for all comparisons). The effect of treatment on PCR conversion varied according to geographic region: in Brazil, the odds ratio for PCR conversion was 3.03 (95% CI, 2.12 to 4.34) at 2 years and 1.87 (95% CI, 1.33 to 2.63) at 5 or more years; in Colombia and El Salvador, the odds ratio was 1.33 (95% CI, 0.90 to 1.98) at 2 years and 0.96 (95% CI, 0.63 to 1.45) at 5 or more years; and in Argentina and Bolivia, the odds ratio was 2.63 (95% CI, 1.89 to 3.66) at 2 years and 2.79 (95% CI, 1.99 to 3.92) at 5 or more years (P<0.001 for interaction). However, the rates of PCR conversion did not correspond to effects on clinical outcome (P=0.16 for interaction). Trypanocidal therapy with benznidazole in patients with

  15. Mortality results from a randomized prostate-cancer screening trial.

    PubMed

    Andriole, Gerald L; Crawford, E David; Grubb, Robert L; Buys, Saundra S; Chia, David; Church, Timothy R; Fouad, Mona N; Gelmann, Edward P; Kvale, Paul A; Reding, Douglas J; Weissfeld, Joel L; Yokochi, Lance A; O'Brien, Barbara; Clapp, Jonathan D; Rathmell, Joshua M; Riley, Thomas L; Hayes, Richard B; Kramer, Barnett S; Izmirlian, Grant; Miller, Anthony B; Pinsky, Paul F; Prorok, Philip C; Gohagan, John K; Berg, Christine D

    2009-03-26

    The effect of screening with prostate-specific-antigen (PSA) testing and digital rectal examination on the rate of death from prostate cancer is unknown. This is the first report from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial on prostate-cancer mortality. From 1993 through 2001, we randomly assigned 76,693 men at 10 U.S. study centers to receive either annual screening (38,343 subjects) or usual care as the control (38,350 subjects). Men in the screening group were offered annual PSA testing for 6 years and digital rectal examination for 4 years. The subjects and health care providers received the results and decided on the type of follow-up evaluation. Usual care sometimes included screening, as some organizations have recommended. The numbers of all cancers and deaths and causes of death were ascertained. In the screening group, rates of compliance were 85% for PSA testing and 86% for digital rectal examination. Rates of screening in the control group increased from 40% in the first year to 52% in the sixth year for PSA testing and ranged from 41 to 46% for digital rectal examination. After 7 years of follow-up, the incidence of prostate cancer per 10,000 person-years was 116 (2820 cancers) in the screening group and 95 (2322 cancers) in the control group (rate ratio, 1.22; 95% confidence interval [CI], 1.16 to 1.29). The incidence of death per 10,000 person-years was 2.0 (50 deaths) in the screening group and 1.7 (44 deaths) in the control group (rate ratio, 1.13; 95% CI, 0.75 to 1.70). The data at 10 years were 67% complete and consistent with these overall findings. After 7 to 10 years of follow-up, the rate of death from prostate cancer was very low and did not differ significantly between the two study groups. (ClinicalTrials.gov number, NCT00002540.) 2009 Massachusetts Medical Society

  16. Determining optimal approaches for weight maintenance: a randomized controlled trial

    PubMed Central

    Dale, Kelly S.; McAuley, Kirsten A.; Taylor, Rachael W.; Williams, Sheila M.; Farmer, Victoria L.; Hansen, Paul; Vorgers, Sue M.; Chisholm, Alexandra W.; Mann, Jim I.

    2009-01-01

    Background Weight regain often occurs after weight loss in overweight individuals. We aimed to compare the effectiveness of 2 support programs and 2 diets of different macronutrient compositions intended to facilitate long-term weight maintenance. Methods Using a 2 × 2 factorial design, we randomly assigned 200 women who had lost 5% or more of their initial body weight to an intensive support program (implemented by nutrition and activity specialists) or to an inexpensive nurse-led program (involving “weigh-ins” and encouragement) that included advice about high-carbohydrate diets or relatively high-monounsaturated-fat diets. Results In total, 174 (87%) participants were followed-up for 2 years. The average weight loss (about 2 kg) did not differ between those in the support programs (0.1 kg, 95% confidence interval [CI] −1.8 to 1.9, p = 0.95) or diets (0.7 kg, 95% CI −1.1 to 2.4, p = 0.46). Total and low-density lipoprotein (LDL) cholesterol levels were significantly higher among those on the high-monounsaturated-fat diet (total cholesterol: 0.17 mmol/L, 95% CI 0.01 to 0.33; p = 0.040; LDL cholesterol: 0.16 mmol/L, 95% CI 0.01 to 0.31; p = 0.039) than among those on the high-carbohydrate diet. Those on the high-monounsaturated-fat diet also had significantly higher intakes of total fat (5% total energy, 95% CI 3% to 6%, p < 0.001) and saturated fat (2% total energy, 95% CI 1% to 2%, p < 0.001). All of the other clinical and laboratory measures were similar among those in the support programs and diets. Interpretation A relatively inexpensive program involving nurse support is as effective as a more resource-intensive program for weight maintenance over a 2-year period. Diets of different macronutrient composition produced comparable beneficial effects in terms of weight loss maintenance. ClinicalTrials.gov trial register no. NCT00128336. PMID:19433812

  17. A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor.

    PubMed

    Elias, W Jeffrey; Lipsman, Nir; Ondo, William G; Ghanouni, Pejman; Kim, Young G; Lee, Wonhee; Schwartz, Michael; Hynynen, Kullervo; Lozano, Andres M; Shah, Binit B; Huss, Diane; Dallapiazza, Robert F; Gwinn, Ryder; Witt, Jennifer; Ro, Susie; Eisenberg, Howard M; Fishman, Paul S; Gandhi, Dheeraj; Halpern, Casey H; Chuang, Rosalind; Butts Pauly, Kim; Tierney, Travis S; Hayes, Michael T; Cosgrove, G Rees; Yamaguchi, Toshio; Abe, Keiichi; Taira, Takaomi; Chang, Jin W

    2016-08-25

    Uncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor. We enrolled patients with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months. Tremor assessments were videotaped and rated by an independent group of neurologists who were unaware of the treatment assignments. The primary outcome was the between-group difference in the change from baseline to 3 months in hand tremor, rated on a 32-point scale (with higher scores indicating more severe tremor). After 3 months, patients in the sham-procedure group could cross over to active treatment (the open-label extension cohort). Seventy-six patients were included in the analysis. Hand-tremor scores improved more after focused ultrasound thalamotomy (from 18.1 points at baseline to 9.6 at 3 months) than after the sham procedure (from 16.0 to 15.8 points); the between-group difference in the mean change was 8.3 points (95% confidence interval [CI], 5.9 to 10.7; P<0.001). The improvement in the thalamotomy group was maintained at 12 months (change from baseline, 7.2 points; 95% CI, 6.1 to 8.3). Secondary outcome measures assessing disability and quality of life also improved with active treatment (the blinded thalamotomy cohort)as compared with the sham procedure (P<0.001 for both comparisons). Adverse events in the thalamotomy group included gait disturbance in 36% of patients and paresthesias or numbness in 38%; these adverse events persisted at 12 months in 9% and 14% of patients, respectively. MRI-guided focused ultrasound thalamotomy reduced hand tremor in patients with essential tremor

  18. A randomized, controlled trial of an aerosolized vaccine against measles.

    PubMed

    Low, Nicola; Bavdekar, Ashish; Jeyaseelan, Lakshmanan; Hirve, Siddhivinayak; Ramanathan, Kavitha; Andrews, Nicholas J; Shaikh, Naseem; Jadi, Ramesh S; Rajagopal, Arunachalam; Brown, Kevin E; Brown, David; Fink, James B; John, Oommen; Scott, Pippa; Riveros-Balta, A Ximena; Greco, Michel; Dhere, Rajeev; Kulkarni, Prasad S; Henao Restrepo, Ana Maria

    2015-04-16

    Aerosolized vaccine can be used as a needle-free method of immunization against measles, a disease that remains a major cause of illness and death. Data on the immunogenicity of aerosolized vaccine against measles in children are inconsistent. We conducted an open-label noninferiority trial involving children 9.0 to 11.9 months of age in India who were eligible to receive a first dose of measles vaccine. Children were randomly assigned to receive a single dose of vaccine by means of either aerosol inhalation or a subcutaneous injection. The primary end points were seropositivity for antibodies against measles and adverse events 91 days after vaccination. The noninferiority margin was 5 percentage points. A total of 1001 children were assigned to receive aerosolized vaccine, and 1003 children were assigned to receive subcutaneous vaccine; 1956 of all the children (97.6%) were followed to day 91, but outcome data were missing for 331 children because of thawed specimens. In the per-protocol population, data on 1560 of 2004 children (77.8%) could be evaluated. At day 91, a total of 662 of 775 children (85.4%; 95% confidence interval [CI], 82.5 to 88.0) in the aerosol group, as compared with 743 of 785 children (94.6%; 95% CI, 92.7 to 96.1) in the subcutaneous group, were seropositive, a difference of -9.2 percentage points (95% CI, -12.2 to -6.3). Findings were similar in the full-analysis set (673 of 788 children in the aerosol group [85.4%] and 754 of 796 children in the subcutaneous group [94.7%] were seropositive at day 91, a difference of -9.3 percentage points [95% CI, -12.3 to -6.4]) and after multiple imputation of missing results. No serious adverse events were attributable to measles vaccination. Adverse-event profiles were similar in the two groups. Aerosolized vaccine against measles was immunogenic, but, at the prespecified margin, the aerosolized vaccine was inferior to the subcutaneous vaccine with respect to the rate of seropositivity. (Funded by the

  19. Echinacea for treating the common cold: A randomized controlled trial

    PubMed Central

    Barrett, Bruce; Brown, Roger; Rakel, Dave; Mundt, Marlon; Bone, Kerry; Barlow, Shari; Ewers, Tola

    2011-01-01

    Background Echinacea is widely used to treat common cold. Objective To assess potential benefits of echinacea as common cold treatment. Design Randomized controlled trial with four parallel groups: 1) no pills, 2) placebo pills (blinded), 3) echinacea pills (blinded), or 4) echinacea pills (open-label). (NCT00065715) Setting Community-based trial. Participants People aged 12 to 80 years with new onset common cold. Interventions Extracts of Echinacea purpurea and E. angustifolia root were used to make tablets standardized to alkamide content. Indistinguishable placebo tablets contained only inert ingredients. Measurements The primary outcome was area-under-the-curve global severity, with severity assessed twice daily by self report on the Wisconsin Upper Respiratory Symptom Survey (WURSS-21). Secondary outcomes included interleukin-8 and neutrophil count from nasal wash assessed at intake and two days later. Results Of 719 enrolled, 713 completed the protocol. Participants were 64% female and 88% white, with mean age 33.7 years. Mean global severity was 236 and 258 for blinded and unblinded echinacea, 264 for blinded placebo, and 286 for those without pills. Contrasting the two blinded groups yields a 28 point (95% CI = −69 to 13) trend toward benefit for echinacea (p=0.089). Mean illness duration for the blinded and unblinded echinacea groups was 6.34 and 6.76 days, respectively, compared to 6.87 days for blinded placebo and 7.03 for no pills. Contrasting blinded groups yields a 0.53 day (95% CI = −1.25 to 0.19) trend toward benefit (p = 0.075). Median change interleukin-8 (pg/mL) and neutrophil cell count were: no pills (30, 1), blinded placebo (39, 1), blinded echinacea (58, 2), and open-label echinacea (70, 1), also not statistically significant. Limitations Higher-than-expected variability limited power to detect small-but-potentially-important benefits. Conclusions The observed shorter illness duration and lower severity seen in the echinacea groups were

  20. Acupuncture for chronic knee pain: a randomized clinical trial.

    PubMed

    Hinman, Rana S; McCrory, Paul; Pirotta, Marie; Relf, Ian; Forbes, Andrew; Crossley, Kay M; Williamson, Elizabeth; Kyriakides, Mary; Novy, Kitty; Metcalf, Ben R; Harris, Anthony; Reddy, Prasuna; Conaghan, Philip G; Bennell, Kim L

    2014-10-01

    There is debate about benefits of acupuncture for knee pain. To determine the efficacy of laser and needle acupuncture for chronic knee pain. Zelen-design clinical trial (randomization occurred before informed consent), in Victoria, Australia (February 2010-December 2012). Community volunteers (282 patients aged ≥50 years with chronic knee pain) were treated by family physician acupuncturists. No acupuncture (control group, n = 71) and needle (n = 70), laser (n = 71), and sham laser (n = 70) acupuncture. Treatments were delivered for 12 weeks. Participants and acupuncturists were blinded to laser and sham laser acupuncture. Control participants were unaware of the trial. Primary outcomes were average knee pain (numeric rating scale, 0 [no pain] to 10 [worst pain possible]; minimal clinically important difference [MCID], 1.8 units) and physical function (Western Ontario and McMaster Universities Osteoarthritis Index, 0 [no difficulty] to 68 [extreme difficulty]; MCID, 6 units) at 12 weeks. Secondary outcomes included other pain and function measures, quality of life, global change, and 1-year follow-up. Analyses were by intention-to-treat using multiple imputation for missing outcome data. At 12 weeks and 1 year, 26 (9%) and 50 (18%) participants were lost to follow-up, respectively. Analyses showed neither needle nor laser acupuncture significantly improved pain (mean difference; -0.4 units; 95% CI, -1.2 to 0.4, and -0.1; 95% CI, -0.9 to 0.7, respectively) or function (-1.7; 95% CI, -6.1 to 2.6, and 0.5; 95% CI, -3.4 to 4.4, respectively) compared with sham at 12 weeks. Compared with control, needle and laser acupuncture resulted in modest improvements in pain (-1.1; 95% CI, -1.8 to -0.4, and -0.8; 95% CI, -1.5 to -0.1, respectively) at 12 weeks, but not at 1 year. Needle acupuncture resulted in modest improvement in function compared with control at 12 weeks (-3.9; 95% CI, -7.7 to -0.2) but was not significantly different from sham (-1.7; 95% CI

  1. Optimizing Treatment of Complicated Grief: A Randomized Clinical Trial.

    PubMed

    Shear, M Katherine; Reynolds, Charles F; Simon, Naomi M; Zisook, Sidney; Wang, Yuanjia; Mauro, Christine; Duan, Naihua; Lebowitz, Barry; Skritskaya, Natalia

    2016-07-01

    To our knowledge, this is the first placebo-controlled randomized clinical trial to evaluate the efficacy of antidepressant pharmacotherapy, with and without complicated grief psychotherapy, in the treatment of complicated grief. To confirm the efficacy of a targeted complicated grief treatment (CGT), determine whether citalopram (CIT) enhances CGT outcome, and examine CIT efficacy without CGT. Included in the study were 395 bereaved adults who met criteria for CG recruited from March 2010 to September 2014 from academic medical centers in Boston, Massachusetts; New York, New York; Pittsburgh, Pennsylvania; and San Diego, California. Co-occurring substance abuse, psychosis, mania, and cognitive impairment were exclusionary. Study participants were randomized using site-specific permuted blocks stratified by major depression into groups prescribed CIT (n = 101), placebo (PLA; n = 99), CGT with CIT (n = 99), and CGT with PLA (n = 96). Independent evaluators conducted monthly assessments for 20 weeks. Response rates were compared under the intention-to-treat principle, including all randomized participants in a logistic regression with inverse probability weighting. All participants received protocolized pharmacotherapy optimized by flexible dosing, psychoeducation, grief monitoring, and encouragement to engage in activities. Half were also randomized to receive manualized CGT in 16 concurrent weekly sessions. Complicated grief-anchored Clinical Global Impression scale measurments every 4 weeks. Response was measured as a rating of "much improved" or "very much improved." Of the 395 study participants, 308 (78.0%) were female and 325 (82.3%) were white. Participants' response to CGT with PLA vs PLA (82.5% vs 54.8%; relative risk [RR], 1.51; 95% CI, 1.16-1.95; P = .002; number needed to treat [NNT], 3.6) suggested the efficacy of CGT, and the addition of CIT did not significantly improve CGT outcome (CGT with CIT vs CGT with PLA: 83.7% vs 82.5%; RR

  2. Placebo Effects and the Common Cold: A Randomized Controlled Trial

    PubMed Central

    Barrett, Bruce; Brown, Roger; Rakel, Dave; Rabago, David; Marchand, Lucille; Scheder, Jo; Mundt, Marlon; Thomas, Gay; Barlow, Shari

    2011-01-01

    PURPOSE We wanted to determine whether the severity and duration of illness caused by the common cold are influenced by randomized assignment to open-label pills, compared with conventional double-blind allocation to active and placebo pills, compared with no pills at all. METHODS We undertook a randomized controlled trial among a population with new-onset common cold. Study participants were allocated to 4 parallel groups: (1) those receiving no pills, (2) those blinded to placebo, (3) those blinded to echinacea, and (4) those given open-label echinacea. Primary outcomes were illness duration and area-under-the-curve global severity. Secondary outcomes included neutrophil count and interleukin 8 levels from nasal wash at intake and 2 days later. RESULTS Of 719 randomized study participants, 2 were lost and 4 exited early. Participants were 64% female, 88% white, and aged 12 to 80 years. Mean illness duration for each group was 7.03 days for those in the no-pill group, 6.87 days for those blinded to placebo, 6.34 days for those blinded to echinacea, and 6.76 days for those in the open-label echinacea group. Mean global severity scores for the 4 groups were no pills, 286; blinded to placebo, 264; blinded to echinacea, 236; and open-label echinacea, 258. Between-group differences were not statistically significant. Comparing the no-pill with blinded to placebo groups, differences (95% confidence interval [CI]) were −0.16 days (95% CI, −0.90 to 0.58 days) for illness duration and −22 severity points (95% CI, −70 to 26 points) for global severity. Comparing the group blinded to echinacea with the open-label echinacea group, differences were 0.42 days (95% CI, −0.28 to 1.12 days) and 22 severity points (95% CI, −19 to 63 points). Median change in interleukin 8 concentration and neutrophil cell count, respectively by group, were 30 pg/mL and 1 cell for the no-pill group, 39 pg/mL and 1 cell for the group binded to placebo, 58 pg/mL and 2 cells for the group

  3. Random assignment in clinical trials: issues in planning (Infant Health and Development Program).

    PubMed

    Kraemer, H C; Fendt, K H

    1990-01-01

    Various options available for the randomization of subjects into groups in a clinical trial are discussed, emphasizing the issues of logistics given less focus in more mathematical treatments. We discuss advantages and disadvantages of total randomization, of Zelen-type randomization procedures, of Efron-type procedures vs more classical blocking procedures to control the balance between groups, and of Simon-Pocock-type procedures vs more classical stratification for controlling possible biases in prognostic factors. Finally, we discuss issues related to choice and implementation of randomization procedures. The discussion is illustrated with the processes of decision-making in a national collaborative randomized clinical trial, the Infant Health and Development Program.

  4. Randomized controlled trials 5: Determining the sample size and power for clinical trials and cohort studies.

    PubMed

    Greene, Tom

    2015-01-01

    Performing well-powered randomized controlled trials is of fundamental importance in clinical research. The goal of sample size calculations is to assure that statistical power is acceptable while maintaining a small probability of a type I error. This chapter overviews the fundamentals of sample size calculation for standard types of outcomes for two-group studies. It considers (1) the problems of determining the size of the treatment effect that the studies will be designed to detect, (2) the modifications to sample size calculations to account for loss to follow-up and nonadherence, (3) the options when initial calculations indicate that the feasible sample size is insufficient to provide adequate power, and (4) the implication of using multiple primary endpoints. Sample size estimates for longitudinal cohort studies must take account of confounding by baseline factors.

  5. Managed problem solving for antiretroviral therapy adherence: a randomized trial.

    PubMed

    Gross, Robert; Bellamy, Scarlett L; Chapman, Jennifer; Han, Xiaoyan; O'Duor, Jacqueline; Palmer, Steven C; Houts, Peter S; Coyne, James C; Strom, Brian L

    2013-02-25

    Adherence to antiretroviral therapy is critical to successful treatment of human immunodeficiency virus (HIV). Few interventions have been demonstrated to improve both adherence and virologic outcomes. We sought to determine whether an intervention derived from problem solving theory, Managed Problem Solving (MAPS), would improve antiretroviral outcomes. We conducted a randomized investigator blind trial of MAPS compared with usual care in HIV-1 infected individuals at 3 HIV clinics in Philadelphia, Pennsylvania. Eligible patients had plasma HIV-1 viral loads greater than 1000 copies/mL and were initiating or changing therapy. Managed Problem Solving consists of 4 in-person and 12 telephone-based meetings with a trained interventionist, then monthly follow-up calls for a year. Primary outcome was medication adherence measured using electronic monitors, summarized as fraction of doses taken quarterly over 1 year. Secondary outcome was undetectable HIV viral load over 1 year. We assessed 218 for eligibility, with 190 eligible and 180 enrolled, 91 randomized to MAPS and 89 to usual care. Fifty-six participants were lost to follow-up: 33 in the MAPS group and 23 in usual care group. In primary intention-to-treat analyses, the odds of being in a higher adherence category was 1.78 (95% CI,1.07-2.96) times greater for MAPS than usual care. In secondary analyses, the odds of an undetectable viral load was 1.48 (95% CI, 0.94-2.31) times greater for MAPS than usual care. In as-treated analyses, the effect of MAPS was stronger for both outcomes. There was neither a difference by prior treatment status nor change in effect over time. Managed Problem Solving is an effective antiretroviral adherence intervention over the first year with a new regimen. It was equally effective at improving adherence in treatment experienced and naïve patients and did not lose effect over time. Implementation of MAPS should be strongly considered where resources are available. clinicaltrials

  6. Aromatherapy as treatment for postoperative nausea: a randomized trial.

    PubMed

    Hunt, Ronald; Dienemann, Jacqueline; Norton, H James; Hartley, Wendy; Hudgens, Amanda; Stern, Thomas; Divine, George

    2013-09-01

    Postoperative nausea (PON) is a common complication of anesthesia and surgery. Antiemetic medication for higher-risk patients may reduce but does not reliably prevent PON. We examined aromatherapy as a treatment for patients experiencing PON after ambulatory surgery. Our primary hypothesis was that in comparison with inhaling a placebo, PON will be reduced significantly by aromatherapy with (1) essential oil of ginger, (2) a blend of essential oils of ginger, spearmint, peppermint, and cardamom, or (3) isopropyl alcohol. Our secondary hypothesis was that the effectiveness of aromatherapy will depend upon the agent used. A randomized trial of aromatherapy with patients who reported nausea in the postanesthesia care unit was conducted at one ambulatory surgical center. Eligibility criteria were adult, able to give consent, and no history of coagulation problems or allergy to the aromatherapy agents. Before surgery, demographic and risk factors were collected. Patients with a nausea level of 1 to 3 on a verbal descriptive scale (0-3) received a gauze pad saturated with a randomly chosen aromatherapy agent and were told to inhale deeply 3 times; nausea (0-3) was then measured again in 5 minutes. Prophylactic and postnausea antiemetics were given as ordered by physicians or as requested by the patient. A total of 1151 subjects were screened for inclusion; 303 subjects reporting nausea were enrolled (26.3%), and 301 meeting protocol were analyzed (26.2%). The change in nausea level was significant for the blend (P < 0.001) and ginger (P = 0.002) versus saline but not for alcohol (P < 0.76). The number of antiemetic medications requested after aromatherapy was also significantly reduced with ginger or blend aromatherapy versus saline (P = 0.002 and P < 0.001, respectively). The hypothesis that aromatherapy would be effective as a treatment for PON was supported. On the basis of our results, future research further evaluating aromatherapy is warranted. Aromatherapy is

  7. Myopia Control with Bifocal Contact Lenses: A Randomized Clinical Trial.

    PubMed

    Aller, Thomas A; Liu, Maria; Wildsoet, Christine F

    2016-04-01

    Most studies have reported only minimal reductions in myopia progression with bifocal or progressive multifocal spectacles, although somewhat larger, although mostly still clinically insignificant, effects have been reported in children with nearpoint esophoria and/or accommodative dysfunctions. The CONTROL study was a 1-year, prospective, randomized, clinical trial of bifocal contact lenses for control of myopia in children with eso fixation disparities at near. Eighty-six myopic subjects, aged 8 to 18 years, were enrolled in the study after passing the screening examination. Of these, 79 completed lens assignment and 78 completed the study. The mean refractive error of these 79 subjects was -2.69 ± 1.40D (SD), and all had progressed by -0.50D or more since their last examination. All subjects also had eso fixation disparity at near. Subjects were randomly assigned to wear either Vistakon Acuvue 2 (single-vision soft contact lenses [SVSCLs]) or Vistakon Acuvue Bifocal (bifocal soft contact lenses [BFSCLs]). Bifocal adds were selected to neutralize the associated phoria. Treatment outcomes included cycloplegic autorefraction and axial length, assessed in terms of changes after 6 and 12 months of treatment from pretreatment baseline values. The BFSCLs significantly slowed myopia progression, with statistically significant differences between the treatment groups after 6 months. After 12 months of treatment, the SVSCL group had progressed by -0.79 ± 0.43D compared with -0.22 ± 0.34D for the BFSCL group (cycloplegic objective spherical equivalent, average of two eyes). Corresponding axial length changes were 0.24 ± 0.17 mm and 0.05 ± 0.14 mm, respectively. All of these differences were found to be statistically significant (unpaired t-tests, p < 0.001). The distance center bifocal contact lenses tested in this study achieved greater control over myopia progression and axial elongation (>70%) compared with most published results with multifocal spectacles. Further

  8. A randomized controlled trial of financial incentives for weight loss

    PubMed Central

    Volpp, Kevin G.; John, Leslie K; Troxel, Andrea B; Norton, Laurie; Fassbender, Jennifer; Loewenstein, George

    2012-01-01

    Context Identifying effective strategies for treating obesity is both a clinical challenge and a public health priority due to the health consequences of obesity. Objective To determine whether common decision errors identified by behavioral economists such as prospect theory, loss aversion, and regret could be used to design an effective weight loss intervention. Design 3-arm randomized controlled trial in which participants were randomized to either usual care (weigh ins once a month) or one of two financial incentives arms. One incentive arm used deposit contracts in which participants put their own money at risk (matched 1:1 by the study) which they would lose if they failed to lose weight. The second used lottery-based incentives in which participants who met the weight loss target had each day a 1 in 5 chance of winning a small reward ($10) and a 1 in 100 chance of winning a large reward ($100). All participants were given a weight loss goal of 1 pound per week for 16 weeks, and results were analyzed using intention-to-treat analysis of variance models. Setting Philadelphia Veterans Affairs Medical Center. Patients 57 patients with BMIs between 30-40 aged between 30 and 70, with no contraindications for study participation. Main Outcome Measures Weight loss after 16 weeks. Results Participants in both incentive groups lost significantly more weight than participants in the control group (3.9 pounds); (Lottery = 13.1 lbs; p-value for lottery vs. control .014; deposit contract = 14.0 lbs, p-value vs. control .003). 47.4% of deposit contract participants and 52.6% of lottery arm participants met the 16-pound weight loss goal compared to 10.5% in the control group (p-value 0.014.). By the end of 7 months, substantial amounts of weight were regained; however, incentive participants weighed significantly less than they did at the study start whereas controls did not. Low lost to follow-up rates (7.0%) during the weight loss phase of the study suggest that both

  9. Amoxicillin for acute rhinosinusitis: A randomized controlled trial

    PubMed Central

    Garbutt, Jane M.; Banister, Christina; Spitznagel, Edward; Piccirillo, Jay F.

    2013-01-01

    Context Evidence to support antibiotic treatment for acute rhinosinusitis is scant, yet antibiotics are commonly used. Objective To determine the incremental effect of amoxicillin treatment over symptomatic treatments for adults with clinically diagnosed acute rhinosinusitis. Design Randomized placebo-controlled trial Participants and Setting Adults with uncomplicated, acute rhinosinusitis were recruited from 10 community practices in Missouri between November 1st 2006 and May 1st 2009 Interventions Ten-day course of either amoxicillin (1500mg/day) or placebo administered in three doses/day. All patients received a 5-7-day supply of symptomatic treatments for pain, fever, cough and nasal congestion to use as needed. Main Outcome Measures The primary outcome was improvement in the disease-specific quality of life after 3–4 days of treatment assessed with the SNOT-16 (minimally important difference 0.5 on 0 to 3 scale). Secondary outcomes included the patients' retrospective assessment of change in sinus symptoms and functional status, recurrence or relapse, satisfaction with and adverse effects of treatment. Outcomes were assessed by telephone interview at Days 3, 7, 10 and 28. Results 166 adults (36% male, 78% Caucasian) were randomized to amoxicillin (85) or placebo (81); 92% concurrently used ≥1 symptomatic treatment (amoxicillin, 94%, placebo 90%, p=0.34). The mean change in SNOT-16 scores was not significantly different between groups on Day 3 (mean difference between groups 0.03, 95% CI −0.12 to 0.19) and Day 10, but differed at Day 7 favoring amoxicillin (mean difference between groups 0.19, 95% CI 0.024 to 0.35). At Day 7 more participants treated with amoxicillin reported symptom improvement (74% vs. 56%, p=0.0205; NNT = 6, 95% CI 3 to 34), with no difference at Day-3 or Day-10. No between group differences were found for any other secondary outcomes. No serious adverse events occurred. Conclusion Among patients with acute rhinosinusitis, a 10-day

  10. Increasing childhood influenza vaccination: a cluster randomized trial.

    PubMed

    Nowalk, Mary Patricia; Lin, Chyongchiou Jeng; Hannibal, Kristin; Reis, Evelyn C; Gallik, Gregory; Moehling, Krissy K; Huang, Hsin-Hui; Allred, Norma J; Wolfson, David H; Zimmerman, Richard K

    2014-10-01

    Since the 2008 inception of universal childhood influenza vaccination, national rates have risen more dramatically among younger children than older children and reported rates across racial/ethnic groups are inconsistent. Interventions may be needed to address age and racial disparities to achieve the recommended childhood influenza vaccination target of 70%. To evaluate an intervention to increase childhood influenza vaccination across age and racial groups. In 2011-2012, a total of 20 primary care practices treating children were randomly assigned to the intervention and control arms of a cluster randomized controlled trial to increase childhood influenza vaccination uptake using a toolkit and other strategies including early delivery of donated vaccine, in-service staff meetings, and publicity. The average vaccination differences from pre-intervention to the intervention year were significantly larger in the intervention arm (n=10 practices) than the control arm (n=10 practices); for children aged 9-18 years (11.1 pct pts intervention vs 4.3 pct pts control, p<0.05); for non-white children (16.7 pct pts intervention vs 4.6 pct pts control, p<0.001); and overall (9.9 pct pts intervention vs 4.2 pct pts control, p<0.01). In multi-level modeling that accounted for person- and practice-level variables and the interactions among age, race, and intervention, the likelihood of vaccination increased with younger age group (6-23 months); white race; commercial insurance; the practice's pre-intervention vaccination rate; and being in the intervention arm. Estimates of the interaction terms indicated that the intervention increased the likelihood of vaccination for non-white children in all age groups and white children aged 9-18 years. A multi-strategy intervention that includes a practice improvement toolkit can significantly improve influenza vaccination uptake across age and racial groups without targeting specific groups, especially in practices with large

  11. Worksite intervention effects on physical health: a randomized controlled trial.

    PubMed

    Atlantis, Evan; Chow, Chin-Moi; Kirby, Adrienne; Fiatarone Singh, Maria A

    2006-09-01

    Overweight and physical inactivity are risk factors for increased disease burden and health care expenditure. Well-designed studies are still needed to determine the treatment efficacy of worksite interventions targeting such risk factors. This randomized controlled trial was conducted at one of Australia's casinos in 2002-2003, to investigate the effects of a comprehensive exercise and lifestyle intervention on physical fitness. Only 6.4% of the workforce expressed interest in being study participants. Seventy-three employees (aged 32 +/- 8 years, 51% overweight/obese, 73% shift workers and 52% women) were recruited and randomized to treatment or wait-list control groups for 24 weeks, 44 of whom completed the intervention. Components of the intervention include supervised moderate-to-high intensity exercise including combined aerobic (at least 20 min duration 3 days/week) and weight-training (for an estimated 30 min completed 2-3 days/week), and dietary/health education (delivered via group seminars, one-on-one counselling and literature through the provision of a worksite manual). ANCOVA, by intention-to-treat and of study completers, found significant between-group differences in the mean waist circumference and predicted maximal oxygen uptake (VO2max), favouring the intervention, but effects were concentrated in one subject. For study completers, between-group differences in the mean waist circumference (82.3 +/- 9.2 versus 90.5 +/- 17.8 cm, p = 0.01) and predicted VO2max (47 versus 41 ml/kg/min, p < 0.001) remained significant without the outlier, favouring the intervention. Higher intervention compliance predicted greater improvements in physical fitness. No significant effects on body mass or body mass index were found. This worksite intervention significantly improved waist circumference and aerobic fitness in healthy but sedentary employees, most of whom were shift workers. Worksite interventions have the potential to counter the increasing burden of

  12. A pilot randomized controlled trial to improve geriatric frailty.

    PubMed

    Chan, Ding-Cheng Derrick; Tsou, Hsiao-Hui; Yang, Rong-Sen; Tsauo, Jau-Yih; Chen, Ching-Yu; Hsiung, Chao Agnes; Kuo, Ken N

    2012-09-25

    Few randomized controlled trials (RCTs) report interventions targeting improvement of frailty status as an outcome. This RCT enrolled 117 older adults (65-79 years of age) in Toufen, Taiwan who scored 3-6 on The Chinese Canadian Study of Health and Aging Clinical Frailty Scale Telephone Version and then score ≥1 on the Cardiovascular Health Study Phenotypic Classification of Frailty (CHS_PCF). With a two by two factorial design, subjects were randomly assigned to interventions (Exercise and nutrition, EN, n = 55 or problem solving therapy, PST, n = 57) or controls (non-EN, n = 62 or non-PST, n = 60). Educational booklets were provided to all. EN group subjects received nutrition consultation and a thrice-weekly exercise-training program while PST group subjects received 6 sessions in 3 month. Subjects were followed at 3, 6, and 12 months. Primary outcome was improvement of the CHS_PCF by at least one category (from pre-frail to robust, or from frail to pre-frail or robust) from baseline assessments. One hundred and one completed final assessments. Intention-to-treat analysis with the generalized estimating equation model was applied with adjustment for time and treatment-by-time interactions. Mean age was 71.4 ± 3.7 years, with 59% females. Baseline characteristic were generally comparable between groups. EN group subjects had a higher improvement rate on the primary outcome than non-EN group subjects (45% vs 27%, adjusted p = 0.008) at 3 months, but not 6 or 12 months. They also had more increase of serum 25(OH) vitamin D level (4.9 ± 7.7 vs 1.2 ± 5.4, p = 0.006) and lower percentage of osteopenia (74% vs 89% p = 0.042) at 12 months. PST group subjects had better improvement (2.7 ± 6.1 vs 0.2 ± 6.7, p = 0.035, 6-month) and less deterioration (-3.5 ± 9.7 vs -7.1 ± 8.7, p = 0.036, 12-month) of dominant leg extension power than non-PST subjects. Some secondary outcomes were also

  13. Prenatal Docosahexaenoic Acid Supplementation and Infant Morbidity: Randomized Controlled Trial

    PubMed Central

    Imhoff-Kunsch, Beth; Stein, Aryeh D.; Martorell, Reynaldo; Parra-Cabrera, Socorro; Romieu, Isabelle

    2011-01-01

    OBJECTIVE: Long-chain polyunsaturated fatty acids such as docosahexaenoic acid (DHA) influence immune function and inflammation; however, the influence of maternal DHA supplementation on infant morbidity is unknown. We investigated the effects of prenatal DHA supplementation on infant morbidity. METHODS: In a double-blind randomized controlled trial conducted in Mexico, pregnant women received daily supplementation with 400 mg of DHA or placebo from 18 to 22 weeks' gestation through parturition. In infants aged 1, 3, and 6 months, caregivers reported the occurrence of common illness symptoms in the preceding 15 days. RESULTS: Data were available at 1, 3, and 6 months for 849, 834, and 834 infants, respectively. The occurrence of specific illness symptoms did not differ between groups; however, the occurrence of a combined measure of cold symptoms was lower in the DHA group at 1 month (OR: 0.76; 95% CI: 0.58–1.00). At 1 month, the DHA group experienced 26%, 15%, and 30% shorter duration of cough, phlegm, and wheezing, respectively, but 22% longer duration of rash (all P ≤ .01). At 3 months, infants in the DHA group spent 14% less time ill (P < .0001). At 6 months, infants in the DHA group experienced 20%, 13%, 54%, 23%, and 25% shorter duration of fever, nasal secretion, difficulty breathing, rash, and “other illness,” respectively, but 74% longer duration of vomiting (all P < .05). CONCLUSIONS: DHA supplementation during pregnancy decreased the occurrence of colds in children at 1 month and influenced illness symptom duration at 1, 3, and 6 months. PMID:21807696

  14. Randomized trial comparing office flexible to rigid cystoscopy in women.

    PubMed

    Quiroz, Lieschen H; Shobeiri, S Abbas; Nihira, Mikio A; Brady, Jordan; Wild, Robert A

    2012-11-01

    The objective of the study was to compare office rigid cystoscopy (RC) versus flexible cystoscopy (FC) in women. This was a prospective randomized trial comparing FC to RC. Aims were to assess 1-week post-procedural complications, compare procedure pain scores, and to assess physician perception of patient discomfort. Pain scores were assessed by visual analogue scale (VAS) and 5-point verbal descriptor scale (VDS). Chi-square was used for categorical comparison and t tests or Wilcoxon test for continuous variables. One hundred women were enrolled. The mean age of participants was 59.7 years (± SD 14.6), and 91 % were Caucasian. This was the first cystoscopy for 86 % of participants. On the 1-week post-procedure questionnaire (85 % response rate), participants in the FC group reported urinary frequency more often than in the RC group (p = 0.041). The FC group reported urgency with urination lasting 1-2 days (p = 0.030) and burning with urination lasting >3 days (p = 0.026), more than the RC group. These symptoms did not persist at 7 days. The duration of the procedure was slightly faster for the FC group (4.6 ± 1.8 min vs 5.7 ± 3.4 min, p = 0.046). Median VAS scores were 0.9 (0.1-2.72) for the FC group and 0.5 (0-2.4) for the RC group (p = 0.505). There were no significant differences between patient or physician perception of pain in either group. Urinary frequency and duration of urinary burning post procedure occurred more frequently in the FC group, although these symptoms were transient. Both office FC and RC are generally well tolerated in women with overall low morbidity.

  15. Dietary fiber supplementation for fecal incontinence: a randomized clinical trial.

    PubMed

    Bliss, Donna Z; Savik, Kay; Jung, Hans-Joachim G; Whitebird, Robin; Lowry, Ann; Sheng, Xiaoyan

    2014-10-01

    Dietary fiber supplements are used to manage fecal incontinence (FI), but little is known about the fiber type to recommend or the level of effectiveness of such supplements, which appears related to the fermentability of the fiber. The aim of this single-blind, randomized controlled trial was to compare the effects of three dietary fiber supplements (carboxymethylcellulose [CMC], gum arabic [GA], or psyllium) with differing levels of fermentability to a placebo in community-living individuals incontinent of loose/liquid feces. The primary outcome was FI frequency; secondary outcomes included FI amount and consistency, supplement intolerance, and quality of life (QoL). Possible mechanisms underlying supplement effects were also examined. After a 14-day baseline, 189 subjects consumed a placebo or 16 g total fiber/day of one of the fiber supplements for 32 days. FI frequency significantly decreased after psyllium supplementation versus placebo, in both intent-to-treat and per-protocol mixed model analyses. CMC increased FI frequency. In intent-to-treat analysis, the number of FI episodes/week after supplementation was estimated to be 5.5 for Placebo, 2.5 for Psyllium, 4.3 for GA, and 6.2 for CMC. Only psyllium consumption resulted in a gel in feces. Supplement intolerance was low. QoL scores did not differ among groups. Patients with FI may experience a reduction in FI frequency after psyllium supplementation, and decreased FI frequency has been shown to be an important personal goal of treatment for patients with FI. Formation of a gel in feces appears to be a mechanism by which residual psyllium improved FI. © 2014 Wiley Periodicals, Inc.

  16. Randomized Controlled Trials of Pediatric Massage: A Review

    PubMed Central

    Moyer, Christopher A.

    2007-01-01

    The existing reviews of massage therapy (MT) research are either limited to infants, adults, or were conducted prior to the publication of the most recent studies using pediatric samples. Randomized controlled trials (RCTs) of pediatric MT are reviewed. A literature search yielded 24 RCTs of pediatric MT, defined as the manual manipulation of soft tissue intended to promote health and well-being in recipients between 2 and 19 years of age. Because RCTs of pediatric MT varied considerably in the amount and types of data reported, quantitative and narrative review methods were both used. Single-dose and multiple-dose effects were examined separately. Among single-dose effects, significant reductions of state anxiety were observed at the first session (g = 0.59, P < 0.05) and the last session (g = 1.10, P < 0.01) of a course of treatment. Effects for salivary cortisol (g = 0.28), negative mood (g = 0.52) and behavior (g = 0.37) were non-significant. Three of eleven multiple-dose effects were statistically significant. These were trait anxiety (g = 0.94, P < 0.05), muscle tone (g = 0.90, P < 0.01) and arthritis pain (g = 1.33, P < 0.01). Results of studies not permitting effect size calculation were judged to be generally consistent with quantitative results. MT benefits pediatric recipients, though not as universally as sometimes reported. Numerous weaknesses endemic to MT research (e.g. low statistical power, frequent failure to report basic descriptive statistics) are identified, and recommendations for future pediatric MT research are discussed. PMID:17342238

  17. Pragmatic Randomized Trials Without Standard Informed Consent?: A National Survey

    PubMed Central

    Nayak, Rahul K; Wendler, David; Miller, Franklin G.; Kim, Scott Y.H.

    2017-01-01

    Background There is significant debate over whether written consent is necessary for low-risk, pragmatic randomized controlled trials (RCT). Objective To assess the U.S. public’s views regarding alternatives to written consent for low-risk pragmatic RCTs. Design National experimental survey (2-by-2 factorial design) examining support for written consent versus general notification or verbal consent in two research scenarios. Setting Web-based survey conducted in December 2014. Participants 2130 U.S. adults sampled from a nationally representative probability-based online panel (response rate, 64%). Measurements Respondent’s recommendation to an ethics review board and personal preference as a potential participant for how to obtain consent/notification in the two research scenarios. Results A majority in each of the four arms (ranging from 60.3% to 71.5%) recommended written informed consent. Personal preferences generally tracked that advice. Most (78.9%) believed the pragmatic RCTs did not pose additional risks but 62.5% of these respondents would still recommend written consent. In contrast, a substantial minority in all arms (28.5% to 39.7%) recommended the alternative option (general notification or verbal consent) over written consent. Limitations Framing effects could impact respondents’ attitudes and non-respondents may differ in levels of trust towards research or healthcare institutions. Conclusions A majority of the public endorsed written informed consent over the most widely considered alternatives for low-risk pragmatic RCTs; however, a substantial minority endorsed general notification or verbal consent. Primary Funding Source Time-sharing Experiments in the Social Sciences and Intramural Research Program of the National Institutes of Health, Clinical Center. PMID:26215125

  18. Dietary Fiber Supplementation for Fecal Incontinence: A Randomized Clinical Trial

    PubMed Central

    Bliss, Donna Z.; Savik, Kay; Jung, Hans-Joachim G.; Whitebird, Robin; Lowry, Ann; Sheng, Xioayan

    2014-01-01

    Dietary fiber supplements are used to manage fecal incontinence (FI), but little is known about the fiber type to recommend or the level of effectiveness of such supplements, which appear related to the fermentability of the fiber. The aim of this single-blind, randomized controlled trial was to compare the effects of three dietary fiber supplements (carboxymethylcellulose [CMC], gum arabic [GA], or psyllium) with differing levels of fermentability to a placebo in community-living individuals incontinent of loose/liquid feces. The primary outcome was FI frequency; secondary outcomes included FI amount and consistency, supplement intolerance, and quality of life (QoL). Possible mechanisms underlying supplement effects were also examined. After a 14-day baseline, 189 subjects consumed a placebo or 16g total fiber/day of one of the fiber supplements for 32 days. FI frequency significantly decreased after psyllium supplementation versus placebo, in both intent-to-treat and per-protocol mixed model analyses. CMC increased FI frequency. In intent-to-treat analysis, the number of FI episodes/week after supplementation was estimated to be 5.5 for Placebo, 2.5 for Psyllium, 4.3 for GA, and 6.2 for CMC. Only psyllium consumption resulted in a gel in feces. Supplement intolerance was low. QoL scores did not differ among groups. Patients with FI may experience a reduction in FI frequency after psyllium supplementation, and decreased FI frequency has been shown to be an important personal goal of treatment for patients with FI. Formation of a gel in feces appears to be a mechanism by which residual psyllium improved FI. PMID:25155992

  19. Identifying randomized clinical trials in Spanish-language dermatology journals.

    PubMed

    Sanclemente, G; Pardo, H; Sánchez, S; Bonfill, X

    2015-06-01

    The necessary foundation for good clinical practice lies in knowledge derived from clinical research. Evidence from randomized clinical trials (RCTs) is the pillar on which decisions about therapy are based. To search exhaustively and rigorously to identify RCTs in dermatology journals published in Spanish. We located dermatology journals through the following search engines and indexes: PubMed, LILACS, SciELO, Periódica, Latindex, Índice Médico Español, C-17, IBECS, EMBASE, and IMBIOMED. We also sought information through dermatology associations and dermatologists in countries where Spanish was the usual language of publication, and we searched the Internet (Google). Afterwards we searched the journals electronically and manually to identify RCTs in all available volumes and issues, checking from the year publication started through 2012. Of 28 journals identified, we included 21 in the search. We found a total of 144 RCTs published since 1969; 78 (54%) were in Latin American journals and 66 (46%) were in Spanish journals. The most frequent disease contexts for RCTs in Spanish journals were psoriasis, mycoses, and acne vulgaris. In Latin American journals, the most frequent disease contexts were common warts, mycoses, acne vulgaris, and skin ulcers on the lower limbs. Manual searches identified more RCTs than electronic searches. Manual searches found a larger number of RCTs. Relatively fewer RCTs are published in Spanish and Latin American journals than in English-language journals. Internet facilitated access to full texts published by many journals; however, free open access to these texts is still unavailable and a large number of journal issues are still not posted online. Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.

  20. Modifying Media Content for Preschool Children: A Randomized Controlled Trial

    PubMed Central

    Garrison, Michelle M.; Herrenkohl, Todd; Haggerty, Kevin; Rivara, Frederick P.; Zhou, Chuan; Liekweg, Kimberly

    2013-01-01

    BACKGROUND: Although previous studies have revealed that preschool-aged children imitate both aggression and prosocial behaviors on screen, there have been few population-based studies designed to reduce aggression in preschool-aged children by modifying what they watch. METHODS: We devised a media diet intervention wherein parents were assisted in substituting high quality prosocial and educational programming for aggression-laden programming without trying to reduce total screen time. We conducted a randomized controlled trial of 565 parents of preschool-aged children ages 3 to 5 years recruited from community pediatric practices. Outcomes were derived from the Social Competence and Behavior Evaluation at 6 and 12 months. RESULTS: At 6 months, the overall mean Social Competence and Behavior Evaluation score was 2.11 points better (95% confidence interval [CI]: 0.78–3.44) in the intervention group as compared with the controls, and similar effects were observed for the externalizing subscale (0.68 [95% CI: 0.06–1.30]) and the social competence subscale (1.04 [95% CI: 0.34–1.74]). The effect for the internalizing subscale was in a positive direction but was not statistically significant (0.42 [95% CI: −0.14 to 0.99]). Although the effect sizes did not noticeably decay at 12 months, the effect on the externalizing subscale was no longer statistically significant (P = .05). In a stratified analysis of the effect on the overall scores, low-income boys appeared to derive the greatest benefit (6.48 [95% CI: 1.60–11.37]). CONCLUSIONS: An intervention to reduce exposure to screen violence and increase exposure to prosocial programming can positively impact child behavior. PMID:23420911

  1. Clinical randomized controlled trial of chemomechanical caries removal (Carisolv).

    PubMed

    Lozano-Chourio, M A; Zambrano, O; González, H; Quero, M

    2006-05-01

    The purpose of this study was to compare the chemomechanical caries-removal system (Carisolv) with high-speed excavation in cavitated occlusal caries of primary molars. Design and setting. The study was a randomized controlled, clinical trial in which the two techniques were compared in each subject. Participants were chosen from public schools, in Maracaibo County, Zulia State, Venezuela. The sample consisted of 80 primary molars selected from 40 children (mean age 7.7+/-0.7 years). Each patient had at least two contralateral primary molars with cavitated occlusal caries and approximately equal-size access to lesions. The outcome variables were: clinically complete caries removal, size of the opening of the cavity, volume of carious tissue removed, pain during caries removal, anaesthesia requested by the patient, caries-removal time, and behaviour and preference of patients. All treated molars were clinically caries free whichever caries-removal procedure was used. When Carisolv' was used the final cavity entrance sizes were smaller (P<0.001) and the estimated volume of tissue removed was less (P<0.001). The time taken for caries removal was three times longer (7.51+/-1.83 min, P<0.001). Some pain was reported by seven (17.5%) participants when Carisolv was used, compared with 16 (40%) when high-speed excavation was used (P<0.05). Using the Carisolv method there was a higher proportion of patients with positive behaviour (P<0.01), and 71.0% (P<0.05) preferred this treatment. Carisolv is an effective clinical alternative treatment for the removal of occlusal dentinal caries in cavitated primary molars; it is more conservative of dental tissue and appeared to be more comfortable for most patients, although the clinical time spent is longer than when using high-speed excavation.

  2. Comparison of two interdental cleaning aids: A randomized clinical trial.

    PubMed

    Bahlmann, L; Frentzen, M; Schroeder, J; Fimmers, R

    2017-07-13

    The aim of this study was a comparison of the handling and acceptance of two kinds of interdental brushes (interdental brush with a handle [HB] and a newly invented interdental cleaning device [NB]). In a randomized crossover trial, 40 test subjects with an average number of 23.5 interdental areas were examined. At two appointments with a "washout" period of one week, the volunteers tried out both cleaning tools (HB and NB). They were asked to clean as many interdental spaces as possible. The percentage of spaces, which could be reached, is the IRI (Interdental Reachability Index). Furthermore, subjective impressions were determined. The average IRI using HB was 64% compared to 80% using of NB (P<.001); 62.5% of the volunteers found the cleaning with HB painful and 15% the cleaning with NB. The subjective feeling after cleaning was 1.75 with NB compared to 2.2 with HB (P=.015), grading the feeling, from 1 for "very good" to 5 for "poor." The acceptance of regular interdental hygiene was rated 1.95 in the case of the NB and 2.85 in the case of the HB. After both appointments, the test subjects declared that they would use the NB 3.05 times and the HB 1.78 times a week. This study shows that the test subjects reached more interdental spaces with NB than with the HB. NB can improve the usage of interdental brushes. Regarding subjective comfort, participants also favoured NB over HB. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Modifying media content for preschool children: a randomized controlled trial.

    PubMed

    Christakis, Dimitri A; Garrison, Michelle M; Herrenkohl, Todd; Haggerty, Kevin; Rivara, Frederick P; Zhou, Chuan; Liekweg, Kimberly

    2013-03-01

    Although previous studies have revealed that preschool-aged children imitate both aggression and prosocial behaviors on screen, there have been few population-based studies designed to reduce aggression in preschool-aged children by modifying what they watch. We devised a media diet intervention wherein parents were assisted in substituting high quality prosocial and educational programming for aggression-laden programming without trying to reduce total screen time. We conducted a randomized controlled trial of 565 parents of preschool-aged children ages 3 to 5 years recruited from community pediatric practices. Outcomes were derived from the Social Competence and Behavior Evaluation at 6 and 12 months. At 6 months, the overall mean Social Competence and Behavior Evaluation score was 2.11 points better (95% confidence interval [CI]: 0.78-3.44) in the intervention group as compared with the controls, and similar effects were observed for the externalizing subscale (0.68 [95% CI: 0.06-1.30]) and the social competence subscale (1.04 [95% CI: 0.34-1.74]). The effect for the internalizing subscale was in a positive direction but was not statistically significant (0.42 [95% CI: -0.14 to 0.99]). Although the effect sizes did not noticeably decay at 12 months, the effect on the externalizing subscale was no longer statistically significant (P = .05). In a stratified analysis of the effect on the overall scores, low-income boys appeared to derive the greatest benefit (6.48 [95% CI: 1.60-11.37]). An intervention to reduce exposure to screen violence and increase exposure to prosocial programming can positively impact child behavior.

  4. Efficacy of Exercise for Menopausal Symptoms: A Randomized Controlled Trial

    PubMed Central

    Sternfeld, Barbara; Guthrie, Katherine A.; Ensrud, Kristine E.; LaCroix, Andrea Z.; Larson, Joseph C.; Dunn, Andrea L.; Anderson, Garnet L.; Seguin, Rebecca A.; Carpenter, Janet S.; Newton, Katherine M.; Reed, Susan D.; Freeman, Ellen W.; Cohen, Lee S.; Joffe, Hadine; Roberts, Melanie; Caan, Bette J.

    2013-01-01

    OBJECTIVE To determine efficacy of exercise training for alleviating vasomotor and other menopausal symptoms. METHODS Late-peri and post-menopausal, sedentary women with frequent vasomotor symptoms (VMS) participated in a randomized controlled trial conducted at three sites: 106 to exercise and 142 to usual activity. The exercise intervention consisted of individual, facility-based aerobic exercise training 3 times/week for 12 weeks. VMS frequency and bother were recorded on daily diaries at baseline and weeks 6 and 12. Intent to treat analyses compared between group differences in changes in VMS frequency and bother, sleep symptoms (Insomnia Severity Index, Pittsburgh Sleep Quality Index) and mood (Patient Health Questionnaire-8 and Generalized Anxiety Disorder-7 questionnaire). RESULTS At the end of week 12, changes in VMS frequency in the exercise group (mean change of −2.4/day, 95% CI −3.0, −1.7) and VMS bother (mean change of −0.5 on a 4 point scale, 95% CI −0.6, −0.4) were not significantly different from those in the control group (−2.6 VMS/day, 95% CI −3.2, −2.0, p=0.43; −0.5 points, 95% CI −0.6, −0.4, p=0.75). The exercise group reported greater improvement in insomnia symptoms (p=0.03), subjective sleep quality (p=0.01), and depressive symptoms (p=0.04), but differences were small and not statistically significant when p values were adjusted for multiple comparisons. Results were similar when considering treatment-adherent women only. CONCLUSION These findings provide strong evidence that 12-weeks of moderate-intensity aerobic exercise does not alleviate VMS but may result in small improvements in sleep quality, insomnia and depression in midlife, sedentary women. PMID:23899828

  5. Transdermal Estradiol Treatment for Postpartum Depression: A Pilot Randomized Trial

    PubMed Central

    Wisner, Katherine L.; Sit, Dorothy K.Y.; Moses-Kolko, Eydie L.; Driscoll, Kara E.; Prairie, Beth; Stika, Catherine S.; Eng, Heather F.; Dills, John L; Luther, James F.; Wisniewski, Stephen R.

    2015-01-01

    Postpartum depression occurs in 14.5% of women in the first three months after birth. This study was an 8 week acute phase randomized trial with three cells (transdermal estradiol (E2), sertraline, and placebo) for the treatment of postpartum major depressive disorder. However, the study was stopped after batch analysis revealed that the E2 serum concentrations were lower than pre-study projections. This paper explores our experiences that will inform future investigations of therapeutic E2 use. Explanations for the low E2 concentrations were: 1) Study patch non-adhesion, which did not explain the low concentrations across the entire sample. 2) Ineffective transdermal patch preparations, although two different patch preparations were used and no significant main effect of patch type on E2 concentrations was found. 3) Obesity, at study entry, E2-treated women had mean ± SD BMI=32.9 ±7.4. No pharmacokinetic data comparing E2 concentrations from transdermal patches in obese women vs. normal weight controls are available. 4) Induction of Cytochrome P450 (CYP450) 3A4 and other E2 elimination pathways in pregnancy. CYP4503A4 is induced in pregnancy and is a pathway for the metabolism of E2. Conversion to estrone and Phase II metabolism via glucuronidation and sulfation, which also increase in pregnancy, are routes of E2 elimination. The time required for these pathways to normalize after delivery has not been elucidated. The observation that transdermal E2 doses greater than 100 mcg/day did not increase serum concentrations was unexpected. Another hypothesis consistent with this observation is suppression of endogenous E2 secretion with increasing exogenous E2 dosing. PMID:26061609

  6. Exercise training and habitual physical activity: a randomized controlled trial.

    PubMed

    Swift, Damon L; Johannsen, Neil M; Tudor-Locke, Catrine; Earnest, Conrad P; Johnson, William D; Blair, Steven N; Sénéchal, Martin; Church, Timothy S

    2012-12-01

    Exercise training reduces adiposity and risk of cardiovascular disease. However, the combined effects of habitual free-living physical activity and aerobic training on waist circumference, weight, fitness, and blood pressure in postmenopausal women are unknown. To evaluate the effects of habitual physical activity levels during aerobic training on weight, waist circumference, fitness, and blood pressure. Secondary analysis of an RCT. Original data collected April 2001 to June 2005 and analyzed in 2012. Postmenopausal women in a supervised exercise trial. Women (n=325) were randomized to 4, 8, or 12 kcal/kg per week of aerobic training or a control group for 6 months. All outcome measures were collected at baseline and follow-up. Changes in dependent variables within each training group were evaluated across tertiles of pedometer-determined habitual physical activity outside exercise training sessions. Changes in waist circumference and weight. Reductions in waist circumference were significantly greater with higher steps/day accumulated outside exercise training compared to lower levels in the 4 (high: -4.8 cm vs low: -1.4 cm, p=0.03); 8 (high: -4.2 cm vs low: -0.4 cm, p=0.03), and 12 kcal/kg per week groups (high: -4.1 cm vs low: -0.7 cm, p=0.05). For all groups, p-trend≤0.03. A trend was observed for greater weight reduction with higher steps/day in the 4 kcal/kg per week group (p-trend=0.04) but not for the other exercise doses. No effects were observed for blood pressure or fitness measures (all p>0.05). In postmenopausal women, higher habitual physical activity while participating in aerobic training was associated with greater reductions in central adiposity, and was supportive of weight loss compared to lower levels. Copyright © 2012 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  7. Job Maintenance through Supported Employment PLUS: A Randomized Controlled Trial.

    PubMed

    Telle, Nils-Torge; Moock, Jörn; Heuchert, Sandra; Schulte, Vivian; Rössler, Wulf; Kawohl, Wolfram

    2016-01-01

    Sickness absence from work due to experienced distress and mental health issues has continuously increased over the past years in Germany. To investigate how this alarming development can be counteracted, we conducted a randomized controlled trial evaluating a job coaching intervention to maintain the working capacity of members of staff and ultimately prevent sickness absence. Our sample included N = 99 employees who reported mental distress due to work-related problems. The intervention group (n = 58) received between 8 and 12 individual job coaching sessions in which they worked with a professional job coach to reduce their mental distress. The control group (n = 41) received a brochure about mental distress. Data were collected before the start of the study, at the end of the job coaching intervention, and at a 3-month follow-up. These data included the number of sickness absence days as the primary outcome and questionnaire measures to assess burnout indicators, life satisfaction, and work-related experiences and behaviors. Compared with the control group, the results indicated no reduction in sickness absence in the intervention group but fewer depressive symptoms, a heightened ability of the participants to distance themselves from work, more experience of work-related success, less depletion of emotional resources, and a greater satisfaction with life when participants had received the job coaching. Thus, although we could not detect a reduction in sickness absence between the groups, job coaching was shown to be a viable intervention technique to benefit employees by contributing to re-establish their mental health. We discuss the implications of the study and outline future research.

  8. Vitamin D and Serum Cytokines in a Randomized Clinical Trial

    PubMed Central

    Yusupov, Eleanor; Li-Ng, Melissa; Pollack, Simcha; Yeh, James K.; Mikhail, Mageda; Aloia, John F.

    2010-01-01

    Background. The role of vitamin D in the body's ability to fight influenza and URI's may be dependent on regulation of specific cytokines that participate in the host inflammatory response. The aim of this study was to test the hypothesis that vitamin D can influence intracellular signaling to regulate the production of cytokines. Subjects and Methods. This study was a 3-month prospective placebo-controlled trial of vitamin D3 supplementation in ambulatory adults [Li-Ng et al., 2009]. 162 volunteers were randomized to receive either 50 μg/d (2000 IU) of vitamin D3 or matching placebo. 25(OH)D and the levels of 10 different cytokines (IL-2, 4, 5, 6, 8, 10, 13, GM-CSF, IFN-γ, TNF-α) were measured in the serum of participants at baseline and the final visit. There were 6 drop-outs from the active vitamin D group and 8 from the placebo group. Results. In the active vitamin D group, we found a significant median percent decline in levels of GM-CSF (−62.9%, P < .0001), IFN-γ (−38.9%, P < .0001), IL-4 (−50.8%, P = .001), IL-8 (−48.4%, P < .0001), and IL-10 (−70.4%, P < .0001). In the placebo group, there were significant declines for GM-CSF (−53.2%, P = .0007) and IFN-γ (−34.4%, P = .0011). For each cytokine, there was no significant difference in the rate of decline between the two groups. 25(OH)D levels increased in the active vitamin D group from a mean of 64.3 ± 25.4 nmol/L to 88.5 ± 23.2 nmol/L. Conclusions. The present study did not show that vitamin D3 supplementation changed circulating cytokine levels among healthy adults. PMID:20871847

  9. Randomized controlled trial of Cassia alata Linn. for constipation.

    PubMed

    Thamlikitkul, V; Bunyapraphatsara, N; Dechatiwongse, T; Theerapong, S; Chantrakul, C; Thanaveerasuwan, T; Nimitnon, S; Boonroj, P; Punkrut, W; Gingsungneon, V

    1990-04-01

    Cassia alata Linn. is a medical plant. Its leaves have been claimed to be effective as a laxative. The studies done so far have shown no toxicity as a result of consuming Cassia alata Linn. leaves. The plant has been found to contain anthraquinones, presumed to be the active ingredient causing the laxative effect. The objective of the study was to test efficacy of Cassia alata Linn. leaves for treatment of constipation compared with a placebo and mist. alba in a multicenter randomized controlled trial carried out in one provincial and 5 community hospitals. Eighty adult patients admitted to 5 community hospitals and one provincial hospital with at least 72 hours of constipation were included in the study. Twenty-eight patients were in the placebo group, 28 in the mist. alba group, and 24 in Cassia alata Linn. group. Each patient was given 120 ml of fluid with caramel color, mist. alba, or Cassia alata Linn. infusion at bed time. Evaluation was performed after 24 hours whether the patient defecated or not. The characteristics of the patients among the three groups were not different. Eighteen per cent of patients in the placebo group passed stools within 24 hours, whereas, 86 and 83 per cent of patients in mist. alba and Cassia alata Linn. groups respectively, passed stools. The differences observed between placebo and mist. alba, placebo and Cassia alata Linn. were statistically highly significant, P less than 0.001 and clinically important. Minimal self-limited side effects, i.e., nausea, dyspepsia, abdominal pain and diarrhea were noted in 16-25 per cent of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Randomized controlled trial of deutetrabenazine for tardive dyskinesia

    PubMed Central

    Factor, Stewart A.; Hauser, Robert A.; Jimenez-Shahed, Joohi; Ondo, William G.; Jarskog, L. Fredrik; Meltzer, Herbert Y.; Woods, Scott W.; Bega, Danny; LeDoux, Mark S.; Shprecher, David R.; Davis, Charles; Davis, Mat D.; Stamler, David; Anderson, Karen E.

    2017-01-01

    Objective: To determine the efficacy and safety of deutetrabenazine as a treatment for tardive dyskinesia (TD). Methods: One hundred seventeen patients with moderate to severe TD received deutetrabenazine or placebo in this randomized, double-blind, multicenter trial. Eligibility criteria included an Abnormal Involuntary Movement Scale (AIMS) score of ≥6 assessed by blinded central video rating, stable psychiatric illness, and stable psychoactive medication treatment. Primary endpoint was the change in AIMS score from baseline to week 12. Secondary endpoints included treatment success at week 12 on the Clinical Global Impression of Change (CGIC) and Patient Global Impression of Change. Results: For the primary endpoint, deutetrabenazine significantly reduced AIMS scores from baseline to week 12 vs placebo (least-squares mean [standard error] −3.0 [0.45] vs −1.6 [0.46], p = 0.019). Treatment success on CGIC (48.2% vs 40.4%) favored deutetrabenazine but was not significant. Deutetrabenazine and placebo groups showed low rates of psychiatric adverse events: anxiety (3.4% vs 6.8%), depressed mood/depression (1.7% vs 1.7%), and suicidal ideation (0% vs 1.7%, respectively). In addition, no worsening in parkinsonism, as measured by the Unified Parkinson's Disease Rating Scale motor subscale, was noted from baseline to week 12 in either group. Conclusions: In patients with TD, deutetrabenazine was well tolerated and significantly reduced abnormal movements. Classification of evidence: This study provides Class I evidence that in patients with TD, deutetrabenazine reduces AIMS scores. PMID:28446646

  11. A Randomized Controlled Trial of Compression Rates during Cardiopulmonary Resuscitation.

    PubMed

    Hwang, Sung Oh; Cha, Kyoung Chul; Kim, Kyuseok; Jo, You Hwan; Chung, Sung Phil; You, Je Sung; Shin, Jonghwan; Lee, Hui Jai; Park, Yoo Seok; Kim, Seunghwan; Choi, Sang Cheon; Park, Eun Jung; Kim, Won Young; Seo, Dong Woo; Moon, Sungwoo; Han, Gapsu; Choi, Han Sung; Kang, Hyunggoo; Park, Seung Min; Kwon, Woon Yong; Choi, Eunhee

    2016-09-01

    The objective of this study was to compare the efficacy of cardiopulmonary resuscitation (CPR) with 120 compressions per minute (CPM) to CPR with 100 CPM in patients with non-traumatic out-of-hospital cardiac arrest. We randomly assigned patients with non-traumatic out-of-hospital cardiac arrest into two groups upon arrival to the emergency department (ED). The patients received manual CPR either with 100 CPM (CPR-100 group) or 120 CPM (CPR-120 group). The primary outcome measure was sustained restoration of spontaneous circulation (ROSC). The secondary outcome measures were survival discharge from the hospital, one-month survival, and one-month survival with good functional status. Of 470 patients with cardiac arrest, 136 patients in the CPR-100 group and 156 patients in the CPR-120 group were included in the final analysis. A total of 69 patients (50.7%) in the CPR-100 group and 67 patients (42.9%) in the CPR-120 group had ROSC (absolute difference, 7.8% points; 95% confidence interval [CI], -3.7 to 19.2%; P = 0.183). The rates of survival discharge from the hospital, one-month survival, and one-month survival with good functional status were not different between the two groups (16.9% vs. 12.8%, P = 0.325; 12.5% vs. 6.4%, P = 0.073; 5.9% vs. 2.6%, P = 0.154, respectively). We did not find differences in the resuscitation outcomes between those who received CPR with 100 CPM and those with 120 CPM. However, a large trial is warranted, with adequate power to confirm a statistically non-significant trend toward superiority of CPR with 100 CPM. ( www.cris.nih.go.kr, cris.nih.go.kr number, KCT0000231).

  12. Behavioral neurocardiac training in hypertension: a randomized, controlled trial.

    PubMed

    Nolan, Robert P; Floras, John S; Harvey, Paula J; Kamath, Markad V; Picton, Peter E; Chessex, Caroline; Hiscock, Natalie; Powell, Jonathan; Catt, Michael; Hendrickx, Hilde; Talbot, Duncan; Chen, Maggie H

    2010-04-01

    It is not established whether behavioral interventions add benefit to pharmacological therapy for hypertension. We hypothesized that behavioral neurocardiac training (BNT) with heart rate variability biofeedback would reduce blood pressure further by modifying vagal heart rate modulation during reactivity and recovery from standardized cognitive tasks ("mental stress"). This randomized, controlled trial enrolled 65 patients with uncomplicated hypertension to BNT or active control (autogenic relaxation), with six 1-hour sessions over 2 months with home practice. Outcomes were analyzed with linear mixed models that adjusted for antihypertensive drugs. BNT reduced daytime and 24-hour systolic blood pressures (-2.4+/-0.9 mm Hg, P=0.009, and -2.1+/-0.9 mm Hg, P=0.03, respectively) and pulse pressures (-1.7+/-0.6 mm Hg, P=0.004, and -1.4+/-0.6 mm Hg, P=0.02, respectively). No effect was observed for controls (P>0.10 for all indices). BNT also increased RR-high-frequency power (0.15 to 0.40 Hz; P=0.01) and RR interval (P<0.001) during cognitive tasks. Among controls, high-frequency power was unchanged (P=0.29), and RR interval decreased (P=0.03). Neither intervention altered spontaneous baroreflex sensitivity (P>0.10). In contrast to relaxation therapy, BNT with heart rate variability biofeedback modestly lowers ambulatory blood pressure during wakefulness, and it augments tonic vagal heart rate modulation. It is unknown whether efficacy of this treatment can be improved with biofeedback of baroreflex gain. BNT, alone or as an adjunct to drug therapy, may represent a promising new intervention for hypertension.

  13. Mobile health, exercise and metabolic risk: a randomized controlled trial.

    PubMed

    Petrella, Robert J; Stuckey, Melanie I; Shapiro, Sheree; Gill, Dawn P

    2014-10-18

    It was hypothesized that a mobile health (mHealth) intervention would elicit greater improvements in systolic blood pressure and other cardiometabolic risk factors at 12 weeks, which would be better maintained over 52 weeks, compared to the active control intervention. Eligible participants (≥2 metabolic syndrome risk factors) were randomized to the mHealth intervention (n = 75) or the active control group (n = 74). Blood pressure and other cardiometabolic risk factors were measured at baseline and at 12, 24 and 52 weeks. Both groups received an individualized exercise prescription and the intervention group additionally received a technology kit for home monitoring of biometrics and physical activity. Analyses were conducted on 67 participants in the intervention group (aged 56.7 ± 9.7 years; 71.6% female) and 60 participants in the active control group (aged 59.1 ± 8.4 years; 76.7% female). At 12 weeks, baseline adjusted mean change in systolic blood pressure (primary outcome) was greater in the active control group compared to the intervention group (-5.68 mmHg; 95% CI -10.86 to -0.50 mmHg; p = 0.03), but there were no differences between groups in mean change for secondary outcomes. Over 52-weeks, the difference in mean change for systolic blood pressure was no longer apparent between groups, but remained significant across the entire population (time: p < 0.001). In participants with increased cardiometabolic risk, exercise prescription alone had greater short-term improvements in systolic blood pressure compared to the mHealth intervention, though over 52 weeks, improvements were equal between interventions. ClinicalTrials.gov http://NCT01944124.

  14. Acceptance and commitment therapy for fibromyalgia: a randomized controlled trial.

    PubMed

    Wicksell, R K; Kemani, M; Jensen, K; Kosek, E; Kadetoff, D; Sorjonen, K; Ingvar, M; Olsson, G L

    2013-04-01

    Fibromyalgia (FM) is characterized by widespread pain and co-morbid symptoms such as fatigue and depression. For FM, medical treatments alone appear insufficient. Recent meta-analyses point to the utility of cognitive behaviour therapy (CBT), but effects are moderate. Within the continuous development of CBT, the empirical support for acceptance and commitment therapy (ACT) has increased rapidly. ACT focuses on improving functioning by increasing the patient's ability to act in accordance with personal values also in the presence of pain and distress (i.e., psychological flexibility). However, no study has yet explored the utility of ACT in FM. To evaluate the efficacy of ACT for FM and the role of psychological inflexibility as a mediator of improvement. In this randomized controlled trial, ACT was evaluated in comparison to a waiting list control condition. Forty women diagnosed with FM participated in the study. Assessments were made pre- and post-treatment and at 3 months of follow-up. The ACT intervention consisted of 12 weekly group sessions. Significant differences in favour of ACT were seen in pain-related functioning, FM impact, mental health-related quality of life, self-efficacy, depression, anxiety and psychological inflexibility. Changes in psychological inflexibility during the course of treatment were found to mediate pre- to follow-up improvements in outcome variables. The results correspond with previous studies on ACT for chronic pain and suggest the utility of ACT for FM as well as the role of psychological inflexibility as a mediator of improvement. © 2012 European Federation of International Association for the Study of Pain Chapters.

  15. Nutrition intervention for migraine: a randomized crossover trial

    PubMed Central

    2014-01-01

    Background Limited evidence suggests that dietary interventions may offer a promising approach for migraine. The purpose of this study was to determine the effects of a low-fat plant-based diet intervention on migraine severity and frequency. Methods Forty-two adult migraine sufferers were recruited from the general community in Washington, DC, and divided randomly into two groups. This 36-week crossover study included two treatments: dietary instruction and placebo supplement. Each treatment period was 16 weeks, with a 4-week washout between. During the diet period, a low-fat vegan diet was prescribed for 4 weeks, after which an elimination diet was used. Participants were assessed at the beginning, midpoint, and end of each period. Significance was determined using student’s t-tests. Results Worst headache pain in last 2 weeks, as measured by visual analog scale, was initially 6.4/10 cm (SD 2.1 cm), and declined 2.1 cm during the diet period and 0.7 cm during the supplement period (p=0.03). Average headache intensity (0–10 scale) was initially 4.2 (SD 1.4) per week, and this declined by 1.0 during the diet period and by 0.5 during the supplement period (p=0.20). Average headache frequency was initially 2.3 (SD 1.8) per week, and this declined by 0.3 during the diet period and by 0.4 during the supplement period (p=0.61). The Patient’s Global Impression of Change showed greater improvement in pain during the diet period (p<0.001). Conclusions These results suggest that a nutritional approach may be a useful part of migraine treatment, but that methodologic issues necessitate further research. Trial registration Clinicaltrials.gov, NCT01699009 and NCT01547494. PMID:25339342

  16. Job Maintenance through Supported Employment PLUS: A Randomized Controlled Trial

    PubMed Central

    Telle, Nils-Torge; Moock, Jörn; Heuchert, Sandra; Schulte, Vivian; Rössler, Wulf; Kawohl, Wolfram

    2016-01-01

    Sickness absence from work due to experienced distress and mental health issues has continuously increased over the past years in Germany. To investigate how this alarming development can be counteracted, we conducted a randomized controlled trial evaluating a job coaching intervention to maintain the working capacity of members of staff and ultimately prevent sickness absence. Our sample included N = 99 employees who reported mental distress due to work-related problems. The intervention group (n = 58) received between 8 and 12 individual job coaching sessions in which they worked with a professional job coach to reduce their mental distress. The control group (n = 41) received a brochure about mental distress. Data were collected before the start of the study, at the end of the job coaching intervention, and at a 3-month follow-up. These data included the number of sickness absence days as the primary outcome and questionnaire measures to assess burnout indicators, life satisfaction, and work-related experiences and behaviors. Compared with the control group, the results indicated no reduction in sickness absence in the intervention group but fewer depressive symptoms, a heightened ability of the participants to distance themselves from work, more experience of work-related success, less depletion of emotional resources, and a greater satisfaction with life when participants had received the job coaching. Thus, although we could not detect a reduction in sickness absence between the groups, job coaching was shown to be a viable intervention technique to benefit employees by contributing to re-establish their mental health. We discuss the implications of the study and outline future research. PMID:27703964

  17. Oxytocin and autism: a systematic review of randomized controlled trials.

    PubMed

    Preti, Antonio; Melis, Mariangela; Siddi, Sara; Vellante, Marcello; Doneddu, Giuseppe; Fadda, Roberta

    2014-03-01

    Little is known about the effectiveness of pharmacological interventions on autism spectrum disorder (ASD). This is a systematic review of the randomized controlled trials (RCTs) of oxytocin interventions in autism, made from January 1990 to September 2013. A search of computerized databases was supplemented by manual search in the bibliographies of key publications. The methodological quality of the studies included in the review was evaluated independently by two researchers, according to a set of formal criteria. Discrepancies in scoring were resolved through discussion. The review yielded seven RCTs, including 101 subjects with ASD (males=95) and 8 males with Fragile X syndrome. The main categories of target symptoms tested in the studies were repetitive behaviors, eye gaze, and emotion recognition. The studies had a medium to high risk of bias. Most studies had small samples (median=15). All the studies but one reported statistically significant between-group differences on at least one outcome variable. Most findings were characterized by medium effect size. Only one study had evidence that the improvement in emotion recognition was maintained after 6 weeks of treatment with intranasal oxytocin. Overall, oxytocin was well tolerated and side effects, when present, were generally rated as mild; however, restlessness, increased irritability, and increased energy occurred more often under oxytocin. RCTs of oxytocin interventions in autism yielded potentially promising findings in measures of emotion recognition and eye gaze, which are impaired early in the course of the ASD condition and might disrupt social skills learning in developing children. There is a need for larger, more methodologically rigorous RCTs in this area. Future studies should be better powered to estimate outcomes with medium to low effect size, and should try to enroll female participants, who were rarely considered in previous studies. Risk of bias should be minimized. Human long

  18. Parent Mentors and Insuring Uninsured Children: A Randomized Controlled Trial

    PubMed Central

    Lin, Hua; Walker, Candy; Lee, Michael; Currie, Janet M.; Allgeyer, Rick; Fierro, Marco; Henry, Monica; Portillo, Alberto; Massey, Kenneth

    2016-01-01

    BACKGROUND: Six million US children are uninsured, despite two-thirds being eligible for Medicaid/Children’s Health Insurance Program (CHIP), and minority children are at especially high risk. The most effective way to insure uninsured children, however, is unclear. METHODS: We conducted a randomized trial of the effects of parent mentors (PMs) on insuring uninsured minority children. PMs were experienced parents with ≥1 Medicaid/CHIP-covered child who received 2 days of training, then assisted families for 1 year with insurance applications, retaining coverage, medical homes, and social needs; controls received traditional Medicaid/CHIP outreach. The primary outcome was obtaining insurance 1 year post-enrollment. RESULTS: We enrolled 237 participants (114 controls; 123 in PM group). PMs were more effective (P< .05 for all comparisons) than traditional methods in insuring children (95% vs 68%), and achieving faster coverage (median = 62 vs 140 days), high parental satisfaction (84% vs 62%), and coverage renewal (85% vs 60%). PM children were less likely to have no primary care provider (15% vs 39%), problems getting specialty care (11% vs 46%), unmet preventive (4% vs 22%) or dental (18% vs 31%) care needs, dissatisfaction with doctors (6% vs 16%), and needed additional income for medical expenses (6% vs 13%). Two years post-PM cessation, more PM children were insured (100% vs 76%). PMs cost $53.05 per child per month, but saved $6045.22 per child insured per year. CONCLUSIONS: PMs are more effective than traditional Medicaid/CHIP methods in insuring uninsured minority children, improving health care access, and achieving parental satisfaction, but are inexpensive and highly cost-effective. PMID:27244706

  19. Phytothermotherapy in osteoarthritis: a randomized controlled clinical trial.

    PubMed

    Fioravanti, Antonella; Bellisai, Barbara; Iacoponi, Francesca; Manica, Patrizia; Galeazzi, Mauro

    2011-05-01

    The aim of this study was to assess the efficacy of adding a cycle of phytothermotherapy (a traditional treatment with fermenting grass used in Trentino-Alto Adige, Italy) to the usual drug treatment, in patients with primary symptomatic osteoarthritis (OA) of the knee, hip, or lumbar spine. In this randomized, single-blind, controlled trial, 218 outpatients were enrolled; 109 patients were treated with a cycle of phytothermotherapy at the thermal resort of Garniga Terme (Trento, Italy) for 10 days; the other 109 patients continued regular outpatient care. Patients were assessed at baseline, after 2 weeks, and after 3 months from the beginning of the study and were evaluated using a visual analogue scale (VAS) for spontaneous pain, a Health Assessment Questionnaire, the Lequesne index for hip and knee osteoarthritis, and the Rolland Morris Questionnaire for lumbar spine OA and symptomatic drug consumption. In patients treated with phytothermotherapy, a significant improvement of VAS and a reduction of nonsteroidal anti-inflammatory drug consumption at the end of treatment and 3 months later were observed. In the control group, no significant differences were noted. The analyses performed separately for each subgroup for OA localization showed that the best results were evident in lumbar spine OA. Concerning tolerability, in the group treated with phytothermotherapy 10% of patients presented side-effects due to treatment, but these were of low intensity and did not interrupt the therapy. In conclusion, the results show beneficial effects of a cycle of phytothermotherapy in patients with OA of the hip, knee, or lumbar spine. Phytothermotherapy may therefore be a useful aid alongside the usual pharmacologic and physiokinesic therapies, or may be used as a valid alternative for patients who do not tolerate pharmacologic treatments.

  20. Ethical and regulatory issues of pragmatic cluster randomized trials in contemporary health systems.

    PubMed

    Anderson, Monique L; Califf, Robert M; Sugarman, Jeremy

    2015-06-01

    Cluster randomized trials randomly assign groups of individuals to examine research questions or test interventions and measure their effects on individuals. Recent emphasis on quality improvement, comparative effectiveness, and learning health systems has prompted expanded use of pragmatic cluster randomized trials in routine health-care settings, which in turn poses practical and ethical challenges that current oversight frameworks may not adequately address. The 2012 Ottawa Statement provides a basis for considering many issues related to pragmatic cluster randomized trials but challenges remain, including some arising from the current US research and health-care regulations. In order to examine the ethical, regulatory, and practical questions facing pragmatic cluster randomized trials in health-care settings, the National Institutes of Health Health Care Systems Research Collaboratory convened a workshop in Bethesda, Maryland, in July 2013. Attendees included experts in clinical trials, patient advocacy, research ethics, and research regulations from academia, industry, the National Institutes of Health Collaboratory, and other federal agencies. Workshop participants identified substantial barriers to implementing these types of cluster randomized trials, including issues related to research design, gatekeepers and governance in health systems, consent, institutional review boards, data monitoring, privacy, and special populations. We describe these barriers and suggest means for understanding and overcoming them to facilitate pragmatic cluster randomized trials in health-care settings.

  1. Effects of the Finnish Alzheimer disease exercise trial (FINALEX): a randomized controlled trial.

    PubMed

    Pitkälä, Kaisu H; Pöysti, Minna M; Laakkonen, Marja-Liisa; Tilvis, Reijo S; Savikko, Niina; Kautiainen, Hannu; Strandberg, Timo E

    2013-05-27

    Few rigorous clinical trials have investigated the effectiveness of exercise on the physical functioning of patients with Alzheimer disease (AD). To investigate the effects of intense and long-term exercise on the physical functioning and mobility of home-dwelling patients with AD and to explore its effects on the use and costs of health and social services. A randomized controlled trial. A total of 210 home-dwelling patients with AD living with their spousal caregiver. The 3 trial arms included (1) group-based exercise (GE; 4-hour sessions with approximately 1-hour training) and (2) tailored home-based exercise (HE; 1-hour training), both twice a week for 1 year, and (3) a control group (CG) receiving the usual community care. The Functional Independence Measure (FIM), the Short Physical Performance Battery, and information on the use and costs of social and health care services. All groups deteriorated in functioning during the year after randomization, but deterioration was significantly faster in the CG than in the HE or GE group at 6 (P = .003) and 12 (P = .015) months. The FIM changes at 12 months were -7.1 (95% CI, -3.7 to -10.5), -10.3 (95% CI, -6.7 to -13.9), and -14.4 (95% CI, -10.9 to -18.0) in the HE group, GE group, and CG, respectively. The HE and GE groups had significantly fewer falls than the CG during the follow-up year. The total costs of health and social services for the HE patient-caregiver dyads (in US dollars per dyad per year) were $25,112 (95% CI, $17,642 to $32,581) (P = .13 for comparison with the CG), $22,066 in the GE group ($15,931 to $28,199; P = .03 vs CG), and $34,121 ($24,559 to $43,681) in the CG. An intensive and long-term exercise program had beneficial effects on the physical functioning of patients with AD without increasing the total costs of health and social services or causing any significant adverse effects. anzctr.org.au Identifier: ACTRN12608000037303.

  2. Anaesthesiological strategies in elective craniotomy: randomized, equivalence, open trial – The NeuroMorfeo trial

    PubMed Central

    Citerio, Giuseppe; Franzosi, Maria Grazia; Latini, Roberto; Masson, Serge; Barlera, Simona; Guzzetti, Stefano; Pesenti, Antonio

    2009-01-01

    Background Many studies have attempted to determine the "best" anaesthetic technique for neurosurgical procedures in patients without intracranial hypertension. So far, no study comparing intravenous (IA) with volatile-based neuroanaesthesia (VA) has been able to demonstrate major outcome differences nor a superiority of one of the two strategies in patients undergoing elective supratentorial neurosurgery. Therefore, current practice varies and includes the use of either volatile or intravenous anaesthetics in addition to narcotics. Actually the choice of the anaestesiological strategy depends only on the anaesthetists' preferences or institutional policies. This trial, named NeuroMorfeo, aims to assess the equivalence between volatile and intravenous anaesthetics for neurosurgical procedures. Methods/Design NeuroMorfeo is a multicenter, randomized, open label, controlled trial, based on an equivalence design. Patients aged between 18 and 75 years, scheduled for elective craniotomy for supratentorial lesion without signs of intracranial hypertension, in good physical state (ASA I-III) and Glasgow Coma Scale (GCS) equal to 15, are randomly assigned to one of three anaesthesiological strategies (two VA arms, sevoflurane + fentanyl or sevoflurane + remifentanil, and one IA, propofol + remifentanil). The equivalence between intravenous and volatile-based neuroanaesthesia will be evaluated by comparing the intervals required to reach, after anaesthesia discontinuation, a modified Aldrete score ≥ 9 (primary end-point). Two statistical comparisons have been planned: 1) sevoflurane + fentanyl vs. propofol + remifentanil; 2) sevoflurane + remifentanil vs. propofol + remifentanil. Secondary end-points include: an assessment of neurovegetative stress based on (a) measurement of urinary catecholamines and plasma and urinary cortisol and (b) estimate of sympathetic/parasympathetic balance by power spectrum analyses of electrocardiographic tracings recorded during anaesthesia

  3. Statin Induced Regression of Cardiomyopathy Trial: A Randomized, Placebo-controlled Double-blind Trial

    PubMed Central

    Hersi, Ahmad; Giannoccaro, J. Peter; Howarth, Andrew; Exner, Derek; Weeks, Sarah; Eitel, Ingo; Herman, R. Cameron; Duff, Henry; Ritchie, Debbie; Mcrae, Maureen; Sheldon, Robert

    2016-01-01

    Background: Hypertrophic cardiomyopathy (HCM), characterized by a thickened, fibrotic myocardium, remains the most common cause of sudden cardiac death in young adults. Based on animal and clinical data, we hypothesized that atorvastatin would induce left ventricular (LV) mass regression. Methods: Statin Induced Regression of Cardiomyopathy Trial (SIRCAT) was a randomized, placebo-controlled study. The primary endpoint was change in LV mass measured by cardiac magnetic resonance imaging 12 months after treatment with once-daily atorvastatin 80 mg or placebo. A key secondary endpoint was diastolic dysfunction measured echocardiographically by transmitral flow velocities. SIRCAT is registered with www.clinicaltrials.gov (NCT00317967). Results: Of 222 screened patients, 22 were randomized evenly to atorvastatin and placebo. The mean age was 47 ± 10 years, and 15 (68%) were male. All subjects completed the protocol. At baseline, LV masses were 197 ± 76 g and 205 ± 82 g in the placebo and atorvastatin groups, respectively. After 12 months treatment, the LV masses in the placebo and atorvastatin groups were 196 ± 80 versus 206 ± 92 g (P = 0.80), respectively. Echocardiographic indices were not different in the two groups at baseline. After 12 months, diastolic dysfunction as assessed using transmitral flow velocities E/E', A/A', and peak systolic mitral velocity showed no benefit from atorvastatin. Conclusions: In patients with HCM, atorvastatin did not cause LV mass regression or improvements in LV diastolic function. PMID:28400935

  4. Central coordination as an alternative for local coordination in a multicenter randomized controlled trial: the FAITH trial experience

    PubMed Central

    2012-01-01

    Background Surgeons in the Netherlands, Canada and the US participate in the FAITH trial (Fixation using Alternative Implants for the Treatment of Hip fractures). Dutch sites are managed and visited by a financed central trial coordinator, whereas most Canadian and US sites have local study coordinators and receive per patient payment. This study was aimed to assess how these different trial management strategies affected trial performance. Methods Details related to obtaining ethics approval, time to trial start-up, inclusion, and percentage completed follow-ups were collected for each trial site and compared. Pre-trial screening data were compared with actual inclusion rates. Results Median trial start-up ranged from 41 days (P25-P75 10-139) in the Netherlands to 232 days (P25-P75 98-423) in Canada (p = 0.027). The inclusion rate was highest in the Netherlands; median 1.03 patients (P25-P75 0.43-2.21) per site per month, representing 34.4% of the total eligible population. It was lowest in Canada; 0.14 inclusions (P25-P75 0.00-0.28), representing 3.9% of eligible patients (p < 0.001). The percentage completed follow-ups was 83% for Canadian and Dutch sites and 70% for US sites (p = 0.217). Conclusions In this trial, a central financed trial coordinator to manage all trial related tasks in participating sites resulted in better trial progression and a similar follow-up. It is therefore a suitable alternative for appointing these tasks to local research assistants. The central coordinator approach can enable smaller regional hospitals to participate in multicenter randomized controlled trials. Circumstances such as available budget, sample size, and geographical area should however be taken into account when choosing a management strategy. Trial Registration ClinicalTrials.gov: NCT00761813 PMID:22225733

  5. Randomized cluster crossover trials for reliable, efficient, comparative effectiveness testing: design of the Prevention of Arrhythmia Device Infection Trial (PADIT).

    PubMed

    Connolly, Stuart J; Philippon, Francois; Longtin, Yves; Casanova, Amparo; Birnie, David H; Exner, Derek V; Dorian, Paul; Prakash, Ratika; Alings, Marco; Krahn, Andrew D

    2013-06-01

    Randomized clinical trials are a major advance in clinical research methodology. However, there are myriad important questions about the effectiveness of treatments used in daily practice that are not informed by the results of randomized trials. This is in part because of important limitations inherent in the methodology of randomized efficacy trials which are performed with tight control of inclusion, exclusion, treatment, and follow-up. This approach enhances evaluation of clinical efficacy (performance in controlled situations) but increases complexity and is not well suited to test clinical effectiveness (performance under conditions of actual use). The cluster crossover trial is a new concept for efficient comparative effectiveness testing. Deep tissue infection occurs in 2% of patients after arrhythmia device implantation, usually requires system extraction, and increases mortality. There is variation in antibiotic prophylaxis used to reduce implanted device infections. To efficiently evaluate the comparative effectiveness of antibiotic strategies now in use, we designed a cluster crossover clinical trial, which randomized implanting centres to 1 of 2 prophylactic antibiotic strategies, which became the standard care at the centre for 6 months, followed by crossover to the other strategy, rerandomization, and second crossover. This method greatly reduces trial complexity because it aligns study procedures with usual clinical care and increases generalizability. Pilot studies have tested the feasibility and an 10,800-patient trial, funded by the Canadian Institutes of Health Research, is now under way. The cluster crossover randomized trial design is well suited to efficiently test comparative effectiveness of existing treatments where there is variability of practice, clinical equipoise, and minimal risk.

  6. Randomized control trial of computer-based rehabilitation of spatial neglect syndrome: the RESPONSE trial protocol.

    PubMed

    Vleet, Thomas Van; DeGutis, Joseph; Dabit, Sawsan; Chiu, Christopher

    2014-02-07

    Spatial neglect is a frequent and debilitating consequence of acquired brain injury and currently has no widely accepted standard of care. While previous interventions for spatial neglect have targeted patients' overt spatial deficits (e.g., reduced contralesional visual scanning), far fewer have directly targeted patients' non-spatial deficits (e.g., sustained attention deficits). Considering that non-spatial deficits have shown to be highly predictive of long-term disability, we developed a novel computer based training program that targets both sustained (tonic) and moment-to-moment (phasic) aspects of non-spatial attention (Tonic and Phasic Alertness Training, TAPAT). Preliminary studies demonstrate that TAPAT is safe and effective in improving both spatial and non-spatial attention deficits in the post-acute recovery phase in neglect patients. The purpose of the current trial (referred to as the REmediation of SPatial Neglect or RESPONSE trial) is to compare TAPAT to an active control training condition, include a larger sample of patients, and assess both cognitive and functional outcomes. We will employ a multi-site, longitudinal, blinded randomized controlled trial (RCT) design with a target sample of 114 patients with spatial neglect. Patients will either perform, at their home, the experimental TAPAT training program or an active control computer games condition for thirty minutes/day, five days a week, over three months. Patients will be assessed on a battery of cognitive and functional outcomes on three occasions: a) immediately before training, b) within forty-eight hours post completion of total training, and c) after a three-month no-contact period post completion of total training, to assess the longevity of potential training effects. The strengths of this protocol are that it tests an innovative, in-home administered treatment that targets a fundamental deficit in neglect, employs highly sensitive computer-based assessments of cognition as well as

  7. Review of Recent Methodological Developments in Group-Randomized Trials: Part 1—Design

    PubMed Central

    Li, Fan; Gallis, John A.; Prague, Melanie; Murray, David M.

    2017-01-01

    In 2004, Murray et al. reviewed methodological developments in the design and analysis of group-randomized trials (GRTs). We have highlighted the developments of the past 13 years in design with a companion article to focus on developments in analysis. As a pair, these articles update the 2004 review. We have discussed developments in the topics of the earlier review (e.g., clustering, matching, and individually randomized group-treatment trials) and in new topics, including constrained randomization and a range of randomized designs that are alternatives to the standard parallel-arm GRT. These include the stepped-wedge GRT, the pseudocluster randomized trial, and the network-randomized GRT, which, like the parallel-arm GRT, require clustering to be accounted for in both their design and analysis. PMID:28426295

  8. Analysis of Factors Affecting Successful Clinical Trial Enrollment in the Context of Three Prospective, Randomized, Controlled Trials.

    PubMed

    Logan, Jennifer K; Tang, Chad; Liao, Zhongxing; Lee, J Jack; Heymach, John V; Swisher, Stephen G; Welsh, James W; Zhang, Jianjun; Lin, Steven H; Gomez, Daniel R

    2017-03-15

    Challenges can arise when attempting to maximize patient enrollment in clinical trials. There have been limited studies focusing on the barriers to enrollment and the efficacy of alternative study design to improve accrual. We analyzed barriers to clinical trial enrollment, particularly the influence of timing, in context of three prospective, randomized oncology trials where one arm was considered more aggressive than the other. From June 2011 to March 2015, patients who were enrolled on 3 prospective institutional protocols (an oligometastatic non-small cell lung cancer [NSCLC] trial and 2 proton vs intensity modulated radiation therapy trials in NSCLC and esophageal cancer) were screened for protocol eligibility. Eligible candidates were approached about trial participation, and patient characteristics (age, sex, T/N categorization) were recorded along with details surrounding trial presentation (appointment number). Fisher's exact test, Student's t tests, and multivariate analysis were performed to assess differences between enrolled and refusal patients. A total of 309 eligible patients were approached about trial enrollment. The enrollment success rate during this time span was 52% (n=160 patients). Enrolled patients were more likely to be presented trial information at an earlier appointment (oligometastatic protocol: 5 vs 3 appointments [P<.001]; NSCLC protocol: 4 vs 3 appointments [P=.0018]; esophageal protocol: 3 vs 2 appointments [P=.0086]). No other factors or patient characteristics significantly affected enrollment success rate. Improvement in enrollment rates for randomized control trials is possible, even in difficult accrual settings. Earlier presentation of trial information to patients is the most influential factor for success and may help overcome accrual barriers without compromising trial design. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. 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.

  10. Depression Prevention Research: Design, Implementation, and Analysis of Randomized Trials.

    ERIC Educational Resources Information Center

    Munoz, Ricardo F.; And Others

    This document contains three papers concerned with prevention intervention research, a new area of depression research which has shown great promise for contributing new knowledge to the understanding of depression. The first paper, "Clinical Trials vs. Prevention Trials: Methodological Issues in Depression Research" (Ricardo F. Munoz), emphasizes…

  11. Central coordination as an alternative for local coordination in a multicenter randomized controlled trial: the FAITH trial experience.

    PubMed

    Zielinski, Stephanie M; Viveiros, Helena; Heetveld, Martin J; Swiontkowski, Marc F; Bhandari, Mohit; Patka, Peter; Van Lieshout, Esther M M

    2012-01-08

    Surgeons in the Netherlands, Canada and the US participate in the FAITH trial (Fixation using Alternative Implants for the Treatment of Hip fractures). Dutch sites are managed and visited by a financed central trial coordinator, whereas most Canadian and US sites have local study coordinators and receive per patient payment. This study was aimed to assess how these different trial management strategies affected trial performance. Details related to obtaining ethics approval, time to trial start-up, inclusion, and percentage completed follow-ups were collected for each trial site and compared. Pre-trial screening data were compared with actual inclusion rates. Median trial start-up ranged from 41 days (P25-P75 10-139) in the Netherlands to 232 days (P2